Not definitive

Evidence ledger

Read the claim and its unfinished work.

Browse all 206 material claims with their exact public-source wording, limitations, source links, medication mappings, and open appraisal controls. The interface does not upgrade provisional evidence into a commissioned result.

206claims in this release

OPEN — NOT DEFINITIVE

Commissioning gates open

Mapped does not mean independently verified.

Release v0.95 is a commissioning-advancement edition. It provides an auditable execution substrate while licensed retrieval, dual extraction, formal appraisal, exact-label reconciliation, and external review remain open.

Independently verified claims: 0 / 206
Completed formal appraisals: 0 / 206
External discipline sign-offs: 0 / 5
Evidence cutoff: 2026-07-29

Prepopulated workbench content does not mean independently extracted, appraised, approved, or complete.
Pregnancy and lactation remain separate clinical questions.
Do not use this evidence export as a basis for abrupt medication discontinuation or a reflexive switch.
The five position fields are execution workbench statements, not individually commissioned universal recommendations.
Public-source certainty descriptors are not formal GRADE ratings.
The normalized claim-to-field mappings are rule-based provisional seeds; independent verification remains pending.

Claim browser

Source-linked claim ledger

Search includes claim wording, IDs, medication names, outcome type, effect text, limitations, and source metadata.

Commissioned & verified

Commissioned and independently verified

Provisional public source

Source-linked public-source wording; commissioning incomplete

Evidence gap

Claim explicitly carries an evidence-gap or insufficiency signal

Integrity-blocked

Excluded or blocked because of the recorded integrity state

Showing all 206 evidence claims

All items are present in the page; filters do not persist.

A-001Module A

Provisional public source

ACOG recommends against withholding or discontinuing a psychiatric medication solely because of pregnancy or lactation.

guideline positionpreconception through lactationStable continuationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: guideline recommendation; not a formal GRADE rating in this module
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation; not a formal GRADE rating in this module
Comparator: continuation versus withholding/discontinuation
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Requires individualized benefit-risk assessment and does not mean every medicine should continue.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024
AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
Doxepin (low-dose insomnia)MED-031
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037
PhenelzineMED-038
TranylcypromineMED-039
IsocarboxazidMED-040
Selegiline (oral)MED-041
Selegiline transdermal systemMED-042
MoclobemideMED-043

Linked sources

guideline position; class evidence synthesis; guideline-linked clinical positionEXT-001 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: 37486661
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-001
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-002Module A

Provisional public source

ACOG considers SSRIs first-line pharmacotherapy for perinatal depression/anxiety and SNRIs reasonable alternatives; prior response should guide selection, with sertraline or escitalopram reasonable for a medication-naive patient.

guideline positionpregnancy and postpartumNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: guideline recommendation; not a formal GRADE rating in this module
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation; not a formal GRADE rating in this module
Comparator: medication choice
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Selection still depends on diagnosis, bipolar screening, severity, comorbidity, interactions, past response, and patient preference.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011

Linked sources

guideline position; class evidence synthesis; guideline-linked clinical positionEXT-001 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: 37486661
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-002
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-003Module A

Provisional public source

In a selected prospective cohort of pregnant patients with recurrent major depression, discontinuation was associated with more relapse than maintenance.

prospective cohortpregnancyStable continuation

Public-source certainty descriptor: moderate for a high-recurrence population; limited generalizability; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for a high-recurrence population; limited generalizability; not GRADE
Comparator: antidepressant discontinuation versus maintenance
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Relapse 68% among 65 discontinuers versus 26% among 82 maintainers.

Limitations

Selected cohort enriched for recurrent illness; nonrandomized treatment decision; not applicable to every patient or drug.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024
AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037
PhenelzineMED-038
TranylcypromineMED-039
IsocarboxazidMED-040
Selegiline transdermal systemMED-042
MoclobemideMED-043

Linked sources

prospective cohortEXT-002 · Not formally appraised

Citation controls

PMID: 16449615
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-003
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-004Module A

Provisional public source

A large Medicaid cohort found no substantial SSRI-associated cardiac-malformation increase after restriction to depression and confounding adjustment; specific historical paroxetine and sertraline signals were attenuated.

adjusted cohortfirst trimesterClinical-position linkage pending

Public-source certainty descriptor: moderate; large adjusted cohort; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate; large adjusted cohort; not GRADE
Comparator: exposed versus unexposed, with depression-restricted analyses
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Paroxetine-RVOTO RR 1.07 (95% CI 0.59-1.93); sertraline-VSD RR 1.04 (0.76-1.41); cohort 949,504 pregnancies.

Limitations

Dispensing does not prove ingestion; live-birth and claims limitations; residual confounding and rare defects remain.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006

Linked sources

adjusted cohortEXT-003 · Not formally appraised

Citation controls

PMID: 24941178
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-004
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-005Module A

Provisional public source

A Nordic cohort found a small adjusted cardiac association for SSRI/venlafaxine exposure that disappeared in sibling comparison, supporting residual familial or illness confounding.

cohort with sibling analysisearly pregnancyUnplanned exposure

Public-source certainty descriptor: moderate for absence of a large class effect; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for absence of a large class effect; not GRADE
Comparator: exposed versus unexposed and discordant siblings
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted any-cardiac OR 1.15 (95% CI 1.05-1.26); sibling OR 0.92 (0.72-1.17).

Limitations

Sibling analysis has lower power and can introduce other bias; agent-specific precision is limited.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007

Linked sources

cohort with sibling analysisEXT-004 · Not formally appraised

Citation controls

PMID: 25888213
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-005
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-006Module A

Provisional public source

Late-pregnancy SSRI exposure may be associated with a small absolute increase in persistent pulmonary hypertension of the newborn; the fully adjusted broad outcome was not statistically significant.

adjusted cohortlate pregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for small absolute risk; residual uncertainty; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for small absolute risk; residual uncertainty; not GRADE
Comparator: late SSRI exposure versus no antidepressant exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

31.5 per 10,000 late-SSRI-exposed versus 20.8 per 10,000 unexposed; adjusted OR 1.10 (0.94-1.29), primary PPHN OR 1.28 (1.01-1.64).

Limitations

Outcome definitions and residual confounding; does not prove causation or identical risk by agent/dose.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006

Linked sources

adjusted cohortEXT-005 · Not formally appraised

Citation controls

PMID: 26034955
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-006
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-007Module A

Provisional public source

Late SSRI exposure was associated with delayed neonatal adaptation in a large term-infant cohort, with dose- and agent-dependent findings.

adjusted cohortlate pregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for association; causality and exact phenotype remain uncertain; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for association; causality and exact phenotype remain uncertain; not GRADE
Comparator: late SSRI exposure versus no SSRI exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

11.2% exposed versus 4.4% unexposed; adjusted OR 2.14 (95% CI 1.96-2.32); 280,090 term infants.

Limitations

Composite outcome; term live births; residual confounding by illness, dose selection, and co-exposure.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006

Linked sources

adjusted cohortEXT-006 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-007
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-008Module A

Provisional public source

A 2026 single-center target-trial emulation found small Apgar reductions and more meconium with SSRI continuation, but no statistically significant increase in NICU admission, congenital anomalies, or other severe outcomes.

target-trial emulationpregnancy continuationStable continuation

Public-source certainty descriptor: low-to-moderate; hypothesis-strengthening, not definitive; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate; hypothesis-strengthening, not definitive; not GRADE
Comparator: continuation versus discontinuation
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

1-minute Apgar mean difference -0.39 (95% CI -0.60 to -0.18); 5-minute -0.28 (-0.42 to -0.13); meconium OR 1.73 (1.22-2.45); NICU OR 1.23 (0.82-1.83); anomalies OR 1.09 (0.63-1.90); n=1,014.

Limitations

Single center; live births; residual confounding; multiple outcomes; modest sample for rare outcomes.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006

Linked sources

target-trial emulationEXT-007 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-008
Required tool: RoB 2
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-009Module A

Provisional public source

Antidepressant exposure near delivery was associated with a small postpartum-hemorrhage increase in a Medicaid mood/anxiety cohort; delivery awareness is warranted, not routine discontinuation.

adjusted cohortnear deliveryStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for association; residual confounding; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for association; residual confounding; not GRADE
Comparator: current exposure versus no current antidepressant
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

PPH 2.8% with no antidepressant, 4.0% with current serotonin reuptake inhibitor, 3.8% with current non-SRI.

Limitations

Claims outcome/exposure; residual severity and obstetric confounding; broad pharmacologic groups.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019

Linked sources

adjusted cohortEXT-008 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-EA2BF8670570 · Unverified metadata

Citation controls

PMID: 23965506
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-009
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-010Module A

Provisional public source

A 2026 systematic review found conventional antidepressant-autism/ADHD associations attenuated or became nonsignificant with illness, familial, genetic, and paternal controls, arguing against a clear causal interpretation.

systematic review and meta-analysisprenatal exposureUnplanned exposure

Public-source certainty descriptor: moderate against a large causal class effect; agent-specific uncertainty; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate against a large causal class effect; agent-specific uncertainty; not GRADE
Comparator: exposed versus unexposed and negative/familial controls
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

37 studies; 648,626 exposed and 24,967,806 unexposed children; conventional ADHD RR 1.35 (1.24-1.47) and autism RR 1.69 (1.24-2.30), attenuated in stronger control designs.

Limitations

Heterogeneous studies and outcomes; residual confounding; does not prove zero risk or resolve individual drugs.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024
AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037

Linked sources

systematic review and meta-analysisEXT-009 · Not formally appraised

Citation controls

PMID: 42134364
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-010
Required tool: AMSTAR 2
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-011Module A

Provisional public source

A large adjusted cohort did not identify duloxetine as a major teratogen, while postpartum hemorrhage and a possible small cardiac signal remained concerns.

adjusted cohortfirst trimester and near deliveryUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for no large overall-malformation increase; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for no large overall-malformation increase; not GRADE
Comparator: duloxetine exposure versus unexposed comparators
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

First-trimester overall-malformation RR 1.11 (95% CI 0.93-1.33); 2,532 first-trimester exposures.

Limitations

Claims data; residual confounding; some outcome estimates imprecise; possible cardiac signal requires replication.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

DuloxetineMED-009

Linked sources

adjusted cohortEXT-010 · Not formally appraised

Citation controls

PMID: 32075794
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-011
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-012Module A

Provisional public source

A Danish matched cohort found no increase in major malformations or spontaneous abortion with mirtazapine.

matched cohortpregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate; uncommon outcomes still possible; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate; uncommon outcomes still possible; not GRADE
Comparator: mirtazapine exposed versus matched unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

1,945 exposed; major malformations 3.5% versus 4.3%, OR 0.81 (95% CI 0.55-1.20); spontaneous abortion HR 1.04 (0.91-1.20).

Limitations

Dispensing exposure; residual confounding; wide intervals for specific defects and neonatal outcomes.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

MirtazapineMED-013

Linked sources

matched cohortEXT-011 · Not formally appraised

Citation controls

PMID: 35320582
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-012
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-013Module A

Provisional public source

One case-control study reported a left-outflow-tract signal after early bupropion exposure, based on few exposed cases.

case-control studyfirst trimesterUnplanned exposure

Public-source certainty descriptor: low for an organ-specific signal; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for an organ-specific signal; not GRADE
Comparator: no bupropion exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted OR 2.6 (95% CI 1.2–5.7); 10 exposed cases.

Limitations

Small exposed count, self-reported exposure, smoking/indication confounding, and multiple comparisons; not replicated consistently and not causal proof.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

BupropionMED-012

Linked sources

case-control studyEXT-012 · Not formally appraised

Citation controls

PMID: 20417496
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-013
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-014Module A

Provisional public source

A prospective ENTIS cohort found no increased major-malformation signal with trazodone relative to SSRI exposure, but confidence intervals were very wide.

prospective cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: low-to-moderate; underpowered; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate; underpowered; not GRADE
Comparator: trazodone versus SSRI exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Major anomalies 1/169 (0.6%) versus 19/730 (2.6%); adjusted OR 0.2 (95% CI 0.03-1.77).

Limitations

Small sample, active comparator, loss to follow-up, and inadequate power for uncommon or specific defects.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

TrazodoneMED-014

Linked sources

prospective cohortEXT-013 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-014
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-015Module A

Provisional public source

Prospective vortioxetine reports remain small; a 2026 registry series had 56 evaluable first-trimester exposures and no major malformations, which cannot exclude uncommon risks.

prospective case seriesfirst trimesterUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low; case-series evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low; case-series evidence; not GRADE
Comparator: no internal comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

56 evaluable first-trimester exposures; no major malformations reported.

Limitations

Small uncontrolled series; referral/selection bias; inadequate for obstetric, neonatal, or neurodevelopmental risk.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

VortioxetineMED-017

Linked sources

prospective case seriesEXT-014 · Not formally appraised

Citation controls

PMID: 42370714
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-015
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-016Module A

Evidence gap

For nefazodone, vilazodone, gepirone ER, dextromethorphan/bupropion, agomelatine, tianeptine, reboxetine, mianserin, and opipramol, available human pregnancy and lactation evidence is inadequate for reliable molecule-specific risk estimates.

evidence gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator cohort
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Heterogeneous international/legacy status; case reports or class analogy cannot establish safety; fixed-combination and unregulated products add uncertainty.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

NefazodoneMED-015
VilazodoneMED-016
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024

Linked sources

claim- or inventory-linked URL; title not extractedURL-42B805EE0F3B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-016
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-017Module A

Provisional public source

Long clinical experience has not established a consistent class-wide major-malformation pattern for tricyclic/tetracyclic antidepressants, but modern molecule-specific adjusted evidence is sparse and maternal anticholinergic, cardiac, overdose, and neonatal effects remain important.

class evidence synthesispregnancy and late gestationDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate by molecule; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate by molecule; not GRADE
Comparator: exposed versus background and disease comparators
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Legacy evidence is heterogeneous; class evidence does not resolve rare agents; dose and indication vary.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
Doxepin (low-dose insomnia)MED-031
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037

Linked sources

guideline position; class evidence synthesis; guideline-linked clinical positionEXT-001 · Not formally appraised
CG192: Antenatal and postnatal mental health: clinical management and service guidanceG-NICE192 · 2014; updated 2020-02-11 · Current after May 2025 surveillance

Citation controls

PMID: 37486661
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-017
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-018Module A

Provisional public source

Doxepin is a poor lactation choice because published reports include probable serious infant toxicity, including respiratory depression or near-apnea, poor feeding, hypotonia, and marked sedation.

lactation case reportslactationDelivery/postpartum/lactation

Public-source certainty descriptor: low for incidence but clinically important signal; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for incidence but clinically important signal; not GRADE
Comparator: no exposed comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Very small number of reports; cannot quantify incidence; applies to the active moiety across dose formulations.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Doxepin (antidepressant-dose oral)MED-030
Doxepin (low-dose insomnia)MED-031

Linked sources

lactation case reportsEXT-015 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-018
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-019Module A

Evidence gap

MAOIs lack robust human pregnancy and lactation cohorts; hypertensive, serotonergic, food, drug, and anesthesia interactions dominate clinical planning.

evidence gap and class safetypregnancy, delivery, and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient reproductive evidence; high interaction certainty; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient reproductive evidence; high interaction certainty; not GRADE
Comparator: no adequate comparator cohort
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Sparse reporting and strong selection; oral/transdermal selegiline and moclobemide are not interchangeable with irreversible MAOIs.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

evidence gap and class safetyEXT-016 · Not formally appraised
CG192: Antenatal and postnatal mental health: clinical management and service guidanceG-NICE192 · 2014; updated 2020-02-11 · Current after May 2025 surveillance

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-019
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-020Module A

Provisional public source

A small lactation pharmacokinetic study found low ketamine and norketamine relative infant doses after single doses.

lactation pharmacokinetic studypostpartum single-dose dosingStable continuationDelivery/postpartum/lactation

Public-source certainty descriptor: low for infant safety; moderate for measured transfer under studied conditions; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for infant safety; moderate for measured transfer under studied conditions; not GRADE
Comparator: dose groups; no unexposed infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Mean RID 0.650% after 0.5 mg/kg and 0.766% after 1 mg/kg.

Limitations

Small sample; limited/no infant ingestion and outcomes; cannot support repeated maintenance treatment or long-term neurodevelopment.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactation pharmacokinetic studyEXT-017 · Not formally appraised

Citation controls

PMID: 35880962
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-020
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-021Module A

Evidence gap

No adequate human cohort evaluates repeated psychiatric-dose ketamine exposure in pregnancy; anesthesia exposure is not a valid proxy for IV, IM, or compounded psychiatric regimens.

evidence gappregnancyUnplanned exposure

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator cohort
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Route, dose, frequency, indication, and compounded-product quality vary; animal findings do not quantify human risk.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

claim- or inventory-linked URL; title not extractedURL-66EF71A9A20F · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-021
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-022Module A

Evidence gap

The current US esketamine label says use is not recommended during pregnancy because human data are insufficient and animal data raise developmental-neurotoxicity concern; it recommends against breastfeeding during treatment.

regulatory labelpregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: regulatory precaution; human risk unquantified; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory precaution; human risk unquantified; not GRADE
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Label language is not evidence of observed human infant harm; REMS, BP, sedation, and dissociation also affect decisions.

Public-source disposition — not a commissioned recommendation

regulatory_update

Open sources, mapped records, and appraisal controls

Mapped medication records

EsketamineMED-047

Linked sources

claim- or inventory-linked URL; title not extractedURL-5CE65F568B3C · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-022
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-023Module A

Provisional public source

FDA withdrew approval of Zulresso (brexanolone) effective 2025-04-14 after the sponsor reported it was no longer marketed and requested withdrawal.

regulatory statuspostpartum treatment availabilityDelivery/postpartum/lactation

Public-source certainty descriptor: high for US regulatory status
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for US regulatory status
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Approval withdrawn effective 2025-04-14.

Limitations

The notice does not identify a new safety finding; this is a marketing/approval status claim, not an efficacy or safety comparison.

Public-source disposition — not a commissioned recommendation

regulatory_update

Open sources, mapped records, and appraisal controls

Mapped medication records

BrexanoloneMED-049

Linked sources

regulatory statusEXT-018 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-023
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-024Module A

Provisional public source

A zuranolone milk study found very low transfer, but did not establish breastfed-infant safety.

regulatory lactation pharmacokineticspostpartum 14-day courseDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for milk transfer; insufficient for infant outcomes; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for milk transfer; insufficient for infant outcomes; not GRADE
Comparator: no infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

n=14; mean RID 0.357%; maximum calculated RID below 1%.

Limitations

Milk was not necessarily fed to infants; no direct infant clinical or neurodevelopmental outcomes.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ZuranoloneMED-050

Linked sources

claim- or inventory-linked URL; title not extractedURL-DA43824191D0 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-024
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-025Module A

Provisional public source

ACOG's 2026 Clinical Practice Update provides focused revised guidance for brexanolone and zuranolone in postpartum depression with onset in the third trimester or within four weeks postpartum; it is a focused update, not a wholesale revision of CPG No. 5.

guideline updatethird trimester and postpartumSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: high for scope and status
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for scope and status
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

The public summary does not substitute for all product-specific counseling; brexanolone US approval is withdrawn.

Public-source disposition — not a commissioned recommendation

regulatory_update

Open sources, mapped records, and appraisal controls

Mapped medication records

BrexanoloneMED-049
ZuranoloneMED-050

Linked sources

guideline updateEXT-019 · Not formally appraised
Clinical Practice Update: Zuranolone and Brexanolone for the Treatment of Postpartum DepressionG-ACOG-CPU26 · Dec 2025 / Jan 2026 · Current; replaces August 2023 Practice Advisory and updates CPG No. 5

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-025
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-026Module A

Provisional public source

A large Korean claims cohort found small adjusted increases in overall and cardiac malformations after first-trimester benzodiazepine exposure, with a dose-response pattern.

adjusted cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate for small association; causality uncertain; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for small association; causality uncertain; not GRADE
Comparator: benzodiazepine exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

40,846 exposed among 3,094,227 pregnancies; major malformations 65.3 versus 51.4 per 1,000, adjusted RR 1.09 (1.05-1.13); heart defects 38.9 versus 27.4 per 1,000, adjusted RR 1.15 (1.10-1.21).

Limitations

Claims exposure, live-birth restriction, residual confounding by indication/severity, and limited molecule-specific precision.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181
BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188

Linked sources

adjusted cohortEXT-020 · Not formally appraised

Citation controls

PMID: 35235572
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-026
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-027Module A

Provisional public source

A Quebec case-time-control study associated early-pregnancy benzodiazepine exposure with spontaneous abortion.

case-time-control cohortearly pregnancyUnplanned exposure

Public-source certainty descriptor: low-to-moderate for association; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate for association; not GRADE
Comparator: exposed versus matched/control intervals
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted OR 1.85 (95% CI 1.61-2.12).

Limitations

Confounding by anxiety, insomnia, severity, smoking, and co-medication may remain; cannot attribute an individual loss to exposure.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181
BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188

Linked sources

case-time-control cohortEXT-021 · Not formally appraised

Citation controls

PMID: 31090881
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-027
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-028Module A

Provisional public source

A prospective pregnancy registry did not find an overall major-malformation increase with benzodiazepines, but was underpowered for specific agents and rare defects.

prospective registryfirst trimesterClinical-position linkage pending

Public-source certainty descriptor: low-to-moderate; wide interval; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate; wide interval; not GRADE
Comparator: benzodiazepine exposed versus psychiatric controls
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Major malformations 3.21% among 151 exposed versus 3.46% among 902 controls; OR 0.92 (95% CI 0.35-2.41).

Limitations

Voluntary registry, modest sample, possible selection bias, and inadequate agent-specific power.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181

Linked sources

prospective registryEXT-022 · Not formally appraised

Citation controls

PMID: 35909254
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-028
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-029Module A

Provisional public source

A 2026 cohort with robust comparison designs did not support an increased risk of offspring psychiatric disorders after prenatal benzodiazepine exposure.

confounding-controlled cohortprenatal exposureUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate against a large causal psychiatric-disorder effect; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate against a large causal psychiatric-disorder effect; not GRADE
Comparator: exposed versus unexposed, sibling and/or negative-control comparisons
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Does not resolve rare outcomes, individual molecules/doses, neonatal toxicity, or all neurodevelopmental domains.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181
BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188

Linked sources

confounding-controlled cohortEXT-023 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-029
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-030Module A

Provisional public source

The 2025 joint benzodiazepine tapering guideline advises against abrupt discontinuation in a dependent patient and calls for maternal-fetal shared decision-making; lorazepam is generally preferred in pregnancy/lactation when a benzodiazepine is necessary.

guideline positionpregnancy and lactationStable continuationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: guideline consensus; not a formal GRADE rating in this module
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline consensus; not a formal GRADE rating in this module
Comparator: supervised taper/continuation versus abrupt stop
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Taper pace and agent choice depend on indication, dependence, seizure risk, prior response, and co-sedatives.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181
BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188

Linked sources

guideline positionEXT-024 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-190E7E54B347 · Unverified metadata

Citation controls

PMID: 40526204
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-030
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-031Module A

Evidence gap

Bromazepam, nitrazepam, lormetazepam, flunitrazepam, prazepam, brotizolam, and etizolam lack robust molecule-specific pregnancy and lactation cohorts; class evidence does not erase accumulation, product-quality, or jurisdictional differences.

evidence gappregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient molecule-specific evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient molecule-specific evidence; not GRADE
Comparator: no adequate molecule-specific comparator cohorts
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Mostly non-US or unregulated exposure; etizolam product identity and contamination may dominate; half-life differs markedly.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188

Linked sources

claim- or inventory-linked URL; title not extractedURL-190E7E54B347 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-031
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-032Module A

Provisional public source

A prospective buspirone registry report observed no malformations among 72 infants, but could not exclude uncommon risks.

prospective registryfirst trimesterDelivery/postpartum/lactation

Public-source certainty descriptor: low; preliminary; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low; preliminary; not GRADE
Comparator: no internal unexposed comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

72 infants; zero malformations reported.

Limitations

Small sample and voluntary registry; insufficient for specific malformations, obstetric, neonatal, or neurodevelopmental outcomes.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

BuspironeMED-189

Linked sources

prospective registryEXT-025 · Not formally appraised

Citation controls

PMID: 35840767
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-032
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-033Module A

Provisional public source

A small buspirone lactation study found low relative infant doses and no reported infant adverse events.

lactation pharmacokinetic studylactationDelivery/postpartum/lactation

Public-source certainty descriptor: low for infant safety; moderate for measured transfer; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for infant safety; moderate for measured transfer; not GRADE
Comparator: no unexposed infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

RID range 0.21%-2.17%.

Limitations

Small sample, short follow-up, and limited infant outcome ascertainment.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

BuspironeMED-189

Linked sources

lactation pharmacokinetic studyEXT-026 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-96B32830EF1A · Unverified metadata

Citation controls

PMID: 38376615
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-033
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-034Module A

Provisional public source

Chronic propranolol exposure may warrant fetal-growth monitoring and near-delivery neonatal heart-rate/glucose observation; milk transfer is low.

class/clinical evidence synthesispregnancy, delivery, and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate; confounded by cardiovascular indication; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate; confounded by cardiovascular indication; not GRADE
Comparator: exposed versus disease comparators
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Beta-blocker studies are heavily confounded by maternal disease; dose and indication vary; not an anxiolytic-efficacy claim.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

PropranololMED-191

Linked sources

class/clinical evidence synthesisEXT-027 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-034
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-035Module A

Provisional public source

A prospective prazosin series of 11 pregnancies was too small to establish safety and found outcomes broadly within expected background patterns.

prospective case seriespregnancyClinical-position linkage pending

Public-source certainty descriptor: very low; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

11 pregnancies; 6 uneventful, 2 miscarriages, and scattered other outcomes.

Limitations

Tiny sample, referral selection, mixed timing/indications, and no power for rare outcomes.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

PrazosinMED-192

Linked sources

prospective case seriesEXT-028 · Not formally appraised

Citation controls

PMID: 37323115
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-035
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-036Module A

Evidence gap

Hydroxyzine has more pregnancy experience than etifoxine, tofisopam, or meprobamate, but all require product-specific counseling; etifoxine/tofisopam evidence is sparse and meprobamate adds dependence, overdose, neonatal-depression, and withdrawal concerns.

evidence synthesis and gappregnancy, delivery, and lactationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient to low-to-moderate by agent; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient to low-to-moderate by agent; not GRADE
Comparator: no adequate common comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Heterogeneous indications and jurisdictions; old meprobamate literature; class substitution is invalid.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

HydroxyzineMED-190
EtifoxineMED-193
TofisopamMED-194
MeprobamateMED-195

Linked sources

claim- or inventory-linked URL; title not extractedURL-A4D502443EC9 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-036
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-037Module A

Provisional public source

A very large 2025 online/2026-print cohort found no overall major-malformation increase with first-trimester Z-drug exposure, but 92.1% of exposures were zolpidem.

adjusted cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate for zolpidem overall malformations; low for other Z-drugs and specific defects; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for zolpidem overall malformations; low for other Z-drugs and specific defects; not GRADE
Comparator: Z-drug exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

4,281,579 pregnancies; 11,652 Medicaid and 10,862 MarketScan exposed; pooled adjusted RR 1.01 (95% CI 0.95-1.08); 92.1% zolpidem.

Limitations

Dispensing exposure, live births, residual confounding, and inadequate power/generalizability for zaleplon, eszopiclone, and zopiclone.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

ZolpidemMED-196
ZaleplonMED-197
EszopicloneMED-198
ZopicloneMED-199

Linked sources

adjusted cohortEXT-029 · Not formally appraised

Citation controls

PMID: 41432941
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-037
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-038Module A

Provisional public source

An older Taiwan cohort associated zolpidem with low birth weight, preterm birth, SGA, and cesarean delivery, but indication and severity confounding limit causal inference.

adjusted cohortpregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate for association; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate for association; not GRADE
Comparator: zolpidem treated versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

2,497 treated versus 12,485 controls; adjusted OR 1.39 (95% CI 1.17–1.64) for low birth weight, 1.49 (1.28–1.74) for preterm birth, 1.34 (1.20–1.49) for SGA, and 1.74 (1.59–1.90) for cesarean delivery.

Limitations

Administrative data; insomnia severity, psychiatric illness, smoking, and co-medication may confound; older practice setting.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ZolpidemMED-196

Linked sources

adjusted cohortEXT-030 · Not formally appraised

Citation controls

PMID: 20686480
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-038
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-039Module A

Evidence gap

A small prospective zopiclone cohort was far too small to exclude major malformations.

prospective cohortfirst trimesterClinical-position linkage pending

Public-source certainty descriptor: very low; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low; not GRADE
Comparator: zopiclone exposed versus comparison
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

0/31 versus 1/37 malformations.

Limitations

Extremely small sample and old study; no precision for specific defects or later outcomes.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

ZopicloneMED-199

Linked sources

prospective cohortEXT-031 · Not formally appraised

Citation controls

PMID: 10458526
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-039
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-040Module A

Evidence gap

Suvorexant lacks adequate human pregnancy outcomes; a single-dose milk study in 12 healthy women found RID below 1% but no direct infant effects were assessed.

regulatory label and lactation PKpregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient pregnancy/infant evidence; moderate for single-dose transfer; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient pregnancy/infant evidence; moderate for single-dose transfer; not GRADE
Comparator: no infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

n=12 single 20-mg dose; RID below 1%.

Limitations

Single dose, healthy volunteers, no repeated use or infant ingestion/outcomes.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

SuvorexantMED-200

Linked sources

claim- or inventory-linked URL; title not extractedURL-35639081D541 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-040
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-041Module A

Evidence gap

Lemborexant lacks adequate human pregnancy outcomes; an eight-participant single-dose milk study recovered 0.0174 mg in milk but did not establish infant safety.

regulatory label and lactation PKpregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient pregnancy/infant evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient pregnancy/infant evidence; not GRADE
Comparator: no infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

n=8 single-dose study; 0.0174 mg recovered in milk.

Limitations

Small single-dose study; no repeated exposure, infant serum, or outcomes.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

LemborexantMED-201

Linked sources

claim- or inventory-linked URL; title not extractedURL-99A46CBA583F · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-041
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-042Module A

Evidence gap

Daridorexant has no adequate human pregnancy or human milk/infant outcome dataset in the reviewed label.

regulatory evidence gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Postmarketing reporting cannot quantify risk; animal data do not establish human effects.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

DaridorexantMED-202

Linked sources

claim- or inventory-linked URL; title not extractedURL-7D14B331FAE5 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-042
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-043Module A

Evidence gap

Ramelteon and tasimelteon lack adequate human pregnancy/lactation cohorts; human melatonin studies have not shown a major signal but were not designed to establish insomnia-treatment safety.

scoping review and regulatory gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient for prescription agonists and long-term supplemental melatonin; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient for prescription agonists and long-term supplemental melatonin; not GRADE
Comparator: heterogeneous or absent comparators
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Melatonin products/doses/indications vary; no insomnia-safety trial and long-term infant neurodevelopment is absent.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

scoping review and regulatory gapEXT-032 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-F749266812B9 · Unverified metadata

Citation controls

PMID: 34730672
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-043
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-044Module A

Provisional public source

Intermittent diphenhydramine, doxylamine, or promethazine exposure has not established a major-malformation pattern, but chronic use adds anticholinergic, tolerance, sedation, delivery, infant-sedation, and possible milk-supply concerns.

class evidence synthesispregnancy, delivery, and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate for no large malformation effect; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate for no large malformation effect; not GRADE
Comparator: exposed versus background
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Evidence often comes from antiemetic/allergy use rather than chronic insomnia; product and dose vary.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

class evidence synthesisEXT-033 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-044
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-045Module A

Provisional public source

A National Birth Defects Prevention Study analysis reported selected cardiac-defect associations with rare periconceptional butalbital exposure, requiring replication; dependence and neonatal barbiturate effects remain clinically important.

case-control studypericonception and late pregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low for specific defects; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for specific defects; not GRADE
Comparator: butalbital exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Rare exposure, multiple comparisons, self-report, combination ingredients, and no established causal pattern.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Butalbital-containing productsMED-209

Linked sources

case-control studyEXT-034 · Not formally appraised

Citation controls

PMID: 24001268
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-045
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-046Module A

Evidence gap

Secobarbital and chloral hydrate are legacy/obsolete sedatives with sparse modern reproductive evidence and important dependence, overdose, respiratory-depression, and withdrawal concerns; avoid initiation and never abruptly stop barbiturate dependence.

legacy evidence and safety gappregnancy, delivery, and lactationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient reproductive evidence; high confidence in dependence/overdose hazard; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient reproductive evidence; high confidence in dependence/overdose hazard; not GRADE
Comparator: no adequate modern comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Old heterogeneous literature and obsolete formulations; chloral hydrate and barbiturates are not interchangeable.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

SecobarbitalMED-210
Chloral hydrateMED-211

Linked sources

claim- or inventory-linked URL; title not extractedURL-D9BFC61FD833 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-046
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-047Module A

Provisional public source

A large US/Nordic cohort found no malformation increase with prescribed amphetamines after adjustment and a possible small cardiac-malformation increase with methylphenidate.

adjusted multinational cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate for no large amphetamine effect; low-to-moderate for small methylphenidate cardiac signal; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for no large amphetamine effect; low-to-moderate for small methylphenidate cardiac signal; not GRADE
Comparator: stimulant exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

US methylphenidate n=2,072: any-malformation RR 1.11 (0.91-1.35), cardiac RR 1.28 (0.94-1.74); amphetamine n=5,571: any RR 1.05 (0.93-1.19), cardiac RR 0.96 (0.78-1.19); pooled methylphenidate cardiac RR 1.28 (1.00-1.64), about 3 additional per 1,000 if causal.

Limitations

Dispensing exposure, live births, residual confounding, and limited formulation-specific evidence; prescription methamphetamine not distinctly characterized.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextroamphetamine (oral)MED-141
Mixed amphetamine saltsMED-142
Amphetamine sulfateMED-143
LisdexamfetamineMED-144
Methamphetamine hydrochloride (prescription)MED-145
Dextroamphetamine transdermal systemMED-146
Methylphenidate immediate-releaseMED-147
Methylphenidate extended-release (non-OROS)MED-148
Methylphenidate OROS extended-releaseMED-149
Methylphenidate transdermal systemMED-150
DexmethylphenidateMED-151
Serdexmethylphenidate/dexmethylphenidateMED-152

Linked sources

adjusted multinational cohort; causal and exposure-boundary statementEXT-035 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-047
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-048Module A

Provisional public source

Medicaid data associated early stimulant exposure with preeclampsia and continuation after 20 weeks with preterm birth; atomoxetine negative-control exposure was not associated.

adjusted cohortearly and late pregnancyStable continuationUnplanned exposure

Public-source certainty descriptor: low-to-moderate for small association; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate for small association; not GRADE
Comparator: exposed versus unexposed and continuation versus discontinuation
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Early stimulant-preeclampsia adjusted RR 1.29 (1.11-1.49); continuation after week 20 versus discontinuation-preterm birth adjusted RR 1.30 (1.10-1.55).

Limitations

Residual confounding by ADHD severity, smoking, healthcare use, and dose; outcome estimates for other endpoints imprecise.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextroamphetamine (oral)MED-141
Mixed amphetamine saltsMED-142
Amphetamine sulfateMED-143
LisdexamfetamineMED-144
Methamphetamine hydrochloride (prescription)MED-145
Dextroamphetamine transdermal systemMED-146
Methylphenidate immediate-releaseMED-147
Methylphenidate extended-release (non-OROS)MED-148
Methylphenidate OROS extended-releaseMED-149
Methylphenidate transdermal systemMED-150
DexmethylphenidateMED-151
Serdexmethylphenidate/dexmethylphenidateMED-152
AtomoxetineMED-154

Linked sources

adjusted cohortEXT-036 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-048
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-049Module A

Provisional public source

A large 2024 cohort found prescribed amphetamine/dextroamphetamine and methylphenidate exposure was not likely to meaningfully increase childhood neurodevelopmental disorders after confounding control.

confounding-controlled cohortprenatal exposureUnplanned exposure

Public-source certainty descriptor: moderate against a large causal effect; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate against a large causal effect; not GRADE
Comparator: exposed versus unexposed and stronger control designs
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Does not resolve rare outcomes, all doses/formulations, prescription methamphetamine, or illicit exposure.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextroamphetamine (oral)MED-141
Mixed amphetamine saltsMED-142
Amphetamine sulfateMED-143
LisdexamfetamineMED-144
Methamphetamine hydrochloride (prescription)MED-145
Dextroamphetamine transdermal systemMED-146
Methylphenidate immediate-releaseMED-147
Methylphenidate extended-release (non-OROS)MED-148
Methylphenidate OROS extended-releaseMED-149
Methylphenidate transdermal systemMED-150
DexmethylphenidateMED-151
Serdexmethylphenidate/dexmethylphenidateMED-152

Linked sources

confounding-controlled cohortEXT-037 · Not formally appraised

Citation controls

PMID: 38265792
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-049
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-050Module A

Evidence gap

Transdermal dextroamphetamine, transdermal methylphenidate, dexmethylphenidate, and serdexmethylphenidate/dexmethylphenidate lack adequate independent reproductive cohorts; active-moiety data are relevant but do not establish route/formulation equivalence.

formulation evidence gappregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient formulation-specific evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient formulation-specific evidence; not GRADE
Comparator: no independent formulation comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Absorption, release system, metabolites, and product-specific exposure differ; class reassurance is indirect.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextroamphetamine transdermal systemMED-146
Methylphenidate transdermal systemMED-150
DexmethylphenidateMED-151
Serdexmethylphenidate/dexmethylphenidateMED-152

Linked sources

claim- or inventory-linked URL; title not extractedURL-FB24D4BECF53 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-050
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-051Module A

Provisional public source

A multinational atomoxetine cohort of about 990 first-trimester exposures found no increase in major overall, cardiac, or limb malformations.

adjusted multinational cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate for no large overall effect; specific risks remain imprecise; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for no large overall effect; specific risks remain imprecise; not GRADE
Comparator: atomoxetine exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Approximately 990 first-trimester exposures; no increase identified in overall, cardiac, or limb malformations.

Limitations

Exposure misclassification, live-birth restrictions, and limited power for specific defects and later outcomes.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

AtomoxetineMED-154

Linked sources

adjusted multinational cohortEXT-038 · Not formally appraised

Citation controls

PMID: 36652686
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-051
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-052Module A

Provisional public source

A 2025 atomoxetine milk study found very low transfer and no reported infant adverse effects, but the sample was small.

lactation pharmacokinetic studylactationDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for measured transfer; low for infant safety; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for measured transfer; low for infant safety; not GRADE
Comparator: no unexposed infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

n=10 taking 40-100 mg/day; mean RID 0.19%; simulated worst-case RID 0.65%.

Limitations

Small, short-term study; simulated worst-case value; inadequate for newborns and neurodevelopment.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

AtomoxetineMED-154

Linked sources

lactation pharmacokinetic studyEXT-039 · Not formally appraised

Citation controls

PMID: 41427840
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-052
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-053Module A

Evidence gap

FDA approved centanafadine for ADHD on 2026-07-24; the July 2026 label states pregnancy clinical-development data are insufficient and there are no human or animal milk data.

regulatory status and evidence gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: high for status; insufficient reproductive evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for status; insufficient reproductive evidence
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

FDA approval date 2026-07-24.

Limitations

Extremely new approval; animal findings cannot quantify human risk; no postmarketing cohort yet.

Public-source disposition — not a commissioned recommendation

regulatory_update

Open sources, mapped records, and appraisal controls

Mapped medication records

CentanafadineMED-153

Linked sources

regulatory status and evidence gapEXT-040 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-3EDFA4FDC021 · Unverified metadata
US/FDA · novel/notable approvalsSUR-05 · Through 2026-07-24 · No

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-053
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-054Module A

Evidence gap

Viloxazine ER has insufficient human pregnancy data; the US label advises discontinuation when pregnancy is recognized unless benefit outweighs risk.

regulatory labelpregnancyStable continuation

Public-source certainty descriptor: regulatory precaution; human risk unquantified; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory precaution; human risk unquantified; not GRADE
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Label language does not establish observed human harm; abrupt change can destabilize function.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Viloxazine extended-releaseMED-155

Linked sources

claim- or inventory-linked URL; title not extractedURL-76884173BC12 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-054
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-055Module A

Provisional public source

A viloxazine milk study found low transfer but did not assess breastfed infants directly.

regulatory lactation pharmacokineticslactationDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for measured transfer; insufficient for infant outcomes; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for measured transfer; insufficient for infant outcomes; not GRADE
Comparator: no infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

n=15; viloxazine RID about 1%; metabolite RID 0.07%.

Limitations

Milk was not fed to infants; no infant serum, clinical effects, or neurodevelopment.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Viloxazine extended-releaseMED-155

Linked sources

claim- or inventory-linked URL; title not extractedURL-76884173BC12 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-055
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-056Module A

Evidence gap

Guanfacine has only very small pregnancy experience and no adequate milk cohort; clonidine has more hypertension-pregnancy experience but ADHD-specific, fetal-growth, hemodynamic, and lactation uncertainties remain. Neither should be stopped abruptly because of rebound hypertension.

evidence gap and pharmacologypregnancy, delivery, and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient for guanfacine; low-to-moderate for selected clonidine outcomes; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient for guanfacine; low-to-moderate for selected clonidine outcomes; not GRADE
Comparator: no adequate ADHD comparator cohort
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Indication and dose differ from hypertension use; maternal disease confounds; milk transfer differs by agent.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

claim- or inventory-linked URL; title not extractedURL-4A15A876209B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-056
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-057Module A

Evidence gap

Amantadine has sparse human pregnancy reports, including anomalous outcomes, and animal findings; absolute human risk is unquantified and it may suppress lactation.

evidence gap and case reportspregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Very small uncontrolled reports, multiple indications/doses, and confounding; animal data cannot establish human causality.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

AmantadineMED-160

Linked sources

claim- or inventory-linked URL; title not extractedURL-5C88C20904DD · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-057
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-058Module A

Provisional public source

Prescribed therapeutic amphetamine evidence must be kept separate from illicit methamphetamine, counterfeit stimulant, high-dose misuse, polysubstance, malnutrition, and disrupted-care evidence.

causal and exposure-boundary statementpregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: high conceptual certainty; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high conceptual certainty; not GRADE
Comparator: prescribed therapeutic exposure versus illicit/nonmedical exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Prescription cohorts do not prove illicit safety; illicit cohorts cannot isolate a therapeutic molecule/dose; prescription methamphetamine has sparse distinct evidence.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextroamphetamine (oral)MED-141
Mixed amphetamine saltsMED-142
Amphetamine sulfateMED-143
LisdexamfetamineMED-144
Methamphetamine hydrochloride (prescription)MED-145
Dextroamphetamine transdermal systemMED-146

Linked sources

adjusted multinational cohort; causal and exposure-boundary statementEXT-035 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-058
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-059Module A

Provisional public source

A Danish registry analysis found a congenital-malformation signal after first-trimester modafinil exposure.

registry cohortfirst trimesterUnplanned exposure

Public-source certainty descriptor: low-to-moderate; concerning but imprecise; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate; concerning but imprecise; not GRADE
Comparator: modafinil versus methylphenidate and unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

6 major malformations among 49 exposed (12%); adjusted OR 3.4 (1.2-9.7) versus methylphenidate and 2.7 (1.1-6.9) versus unexposed.

Limitations

Only 49 exposures, wide intervals, residual confounding, and possible surveillance/selection effects.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ModafinilMED-161
ArmodafinilMED-162

Linked sources

registry cohortEXT-041 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-059
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-060Module A

Provisional public source

A US modafinil/armodafinil pregnancy registry reported a high major-malformation proportion, but voluntary enrollment and absence of an internal comparator severely limit inference.

prospective registry case seriesfirst trimesterUnplanned exposure

Public-source certainty descriptor: low; signal-generating; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low; signal-generating; not GRADE
Comparator: no internal comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

13 major malformations among 102 prospective live births (13%).

Limitations

Small voluntary registry, live-birth restriction, loss/selection, no internal comparator, and mixed modafinil/armodafinil exposure.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ModafinilMED-161
ArmodafinilMED-162

Linked sources

prospective registry case seriesEXT-042 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-060
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-061Module A

Provisional public source

A Scandinavian cohort did not find a modafinil malformation increase, but the estimate was extremely imprecise and does not negate other signals.

registry cohortfirst trimesterClinical-position linkage pending

Public-source certainty descriptor: very low-to-low; wide interval; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low-to-low; wide interval; not GRADE
Comparator: modafinil exposed versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

RR 0.63 (95% CI 0.09-4.40).

Limitations

Small exposed sample and confidence interval compatible with substantial harm or benefit.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ModafinilMED-161
ArmodafinilMED-162

Linked sources

registry cohortEXT-043 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-061
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-062Module A

Provisional public source

The UK MHRA advises that modafinil should not be used in pregnancy, recommends effective contraception during treatment and for two months after stopping, and warns it can reduce steroidal contraceptive effectiveness.

regulatory warningpreconception and pregnancySwitch before conception

Public-source certainty descriptor: high for UK regulatory position; not a US contraindication
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for UK regulatory position; not a US contraindication
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Contraception advised during treatment and for 2 months after stopping.

Limitations

Jurisdiction-specific; armodafinil inference is related but not identical; individual narcolepsy safety must be addressed.

Public-source disposition — not a commissioned recommendation

regulatory_update

Open sources, mapped records, and appraisal controls

Mapped medication records

ModafinilMED-161
ArmodafinilMED-162

Linked sources

regulatory warningEXT-044 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-062
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-063Module A

Provisional public source

Single-case lactation reports estimated modest modafinil/armodafinil relative infant doses, but cannot establish infant safety.

lactation case reportslactationDelivery/postpartum/lactation

Public-source certainty descriptor: very low for infant safety; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for infant safety; not GRADE
Comparator: no comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Modafinil RID 5.3% in one case; armodafinil RID 4.85% in one case.

Limitations

One case per estimate, uncertain enantiomer accounting, limited infant outcomes, and no long-term follow-up.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

ModafinilMED-161
ArmodafinilMED-162

Linked sources

lactation case reportsEXT-045 · Not formally appraised

Citation controls

PMID: 30518447
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-063
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-064Module A

Evidence gap

Solriamfetol has no adequate human pregnancy cohort or human milk/infant outcome dataset in the reviewed public label; BP and heart-rate effects remain relevant.

regulatory evidence gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Label may not capture all later postmarketing reports; no controlled human reproductive study.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

SolriamfetolMED-163

Linked sources

claim- or inventory-linked URL; title not extractedURL-75CE2459518F · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-064
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-065Module A

Evidence gap

Pitolisant has insufficient human pregnancy evidence; a label milk study estimated very low transfer but did not establish infant safety.

regulatory label and lactation PKpregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient pregnancy evidence; moderate for milk transfer; low for infant safety; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient pregnancy evidence; moderate for milk transfer; low for infant safety; not GRADE
Comparator: no infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Mean infant dose 0.009 mg/day; RID below 1%.

Limitations

No direct infant outcomes; QT and drug/contraceptive interactions influence decisions.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

PitolisantMED-164

Linked sources

claim- or inventory-linked URL; title not extractedURL-94500AB9F747 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-065
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-066Module A

Evidence gap

Oxybate products lack adequate human pregnancy outcome cohorts; GHB is excreted into human milk and infant safety is insufficiently characterized. Formulations differ in sodium load, schedule, and release.

regulatory evidence gappregnancy, delivery, and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient reproductive evidence; high confidence in CNS-depressant interaction risk; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient reproductive evidence; high confidence in CNS-depressant interaction risk; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Do not generalize a timing strategy across immediate-release, mixed-salt, and extended-release products; severe narcolepsy/cataplexy also creates risk.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

Sodium oxybate immediate-releaseMED-165
Calcium/magnesium/potassium/sodium oxybatesMED-166
Sodium oxybate extended-releaseMED-167

Linked sources

claim- or inventory-linked URL; title not extractedURL-8715D4E0307D · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-066
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-067Module A

Provisional public source

FDA prescription labeling uses narrative Pregnancy and Lactation Labeling Rule sections rather than the former A/B/C/D/X letter categories.

regulatory frameworkpregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: high for US regulatory framework
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for US regulatory framework
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Exact labeling and revision date remain product-specific; non-US systems differ.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024
AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
Doxepin (low-dose insomnia)MED-031
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037
PhenelzineMED-038
TranylcypromineMED-039
IsocarboxazidMED-040
Selegiline (oral)MED-041
Selegiline transdermal systemMED-042
MoclobemideMED-043
Ketamine (intravenous psychiatric use)MED-044
Ketamine (intramuscular psychiatric use)MED-045
Ketamine (compounded oral/nasal/other psychiatric formulations)MED-046
EsketamineMED-047
Dextromethorphan (standalone/off-label psychiatric use)MED-048
BrexanoloneMED-049
ZuranoloneMED-050
LiothyronineMED-051
PramipexoleMED-052
L-methylfolate (prescription medical food)MED-054
S-adenosyl-L-methionineMED-055
Lorazepam injectionMED-139
Diphenhydramine injectionMED-140
Dextroamphetamine (oral)MED-141
Mixed amphetamine saltsMED-142
Amphetamine sulfateMED-143
LisdexamfetamineMED-144
Methamphetamine hydrochloride (prescription)MED-145
Dextroamphetamine transdermal systemMED-146
Methylphenidate immediate-releaseMED-147
Methylphenidate extended-release (non-OROS)MED-148
Methylphenidate OROS extended-releaseMED-149
Methylphenidate transdermal systemMED-150
DexmethylphenidateMED-151
Serdexmethylphenidate/dexmethylphenidateMED-152
CentanafadineMED-153
AtomoxetineMED-154
Viloxazine extended-releaseMED-155
Guanfacine immediate-releaseMED-156
Guanfacine extended-releaseMED-157
Clonidine immediate-releaseMED-158
Clonidine extended-releaseMED-159
AmantadineMED-160
ModafinilMED-161
ArmodafinilMED-162
SolriamfetolMED-163
PitolisantMED-164
Sodium oxybate immediate-releaseMED-165
Calcium/magnesium/potassium/sodium oxybatesMED-166
Sodium oxybate extended-releaseMED-167
AlprazolamMED-168
LorazepamMED-169
OxazepamMED-170
TemazepamMED-171
DiazepamMED-172
ClonazepamMED-173
ChlordiazepoxideMED-174
ClorazepateMED-175
TriazolamMED-176
EstazolamMED-177
FlurazepamMED-178
QuazepamMED-179
MidazolamMED-180
ClobazamMED-181
BromazepamMED-182
NitrazepamMED-183
LormetazepamMED-184
FlunitrazepamMED-185
PrazepamMED-186
BrotizolamMED-187
EtizolamMED-188
BuspironeMED-189
HydroxyzineMED-190
PropranololMED-191
PrazosinMED-192
EtifoxineMED-193
TofisopamMED-194
MeprobamateMED-195
ZolpidemMED-196
ZaleplonMED-197
EszopicloneMED-198
ZopicloneMED-199
SuvorexantMED-200
LemborexantMED-201
DaridorexantMED-202
RamelteonMED-203
TasimelteonMED-204
Melatonin (nonprescription)MED-205
DiphenhydramineMED-206
DoxylamineMED-207
PromethazineMED-208
Butalbital-containing productsMED-209
SecobarbitalMED-210
Chloral hydrateMED-211

Linked sources

regulatory frameworkEXT-046 · Not formally appraised
Pregnancy and Lactation Labeling Rule resourcesR-FDA-PLLR · Final rule 2014; effective 2015-06-30 · Current framework

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-067
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-068Module A

Provisional public source

Sertraline and paroxetine generally have the lowest SSRI milk transfer and are often preferred for new lactation starts; fluoxetine has higher/longer-lived exposure, but a stable effective regimen should not be switched automatically.

LactMed synthesislactationStable continuationNew initiationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for relative milk-transfer pattern; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for relative milk-transfer pattern; not GRADE
Comparator: between-agent milk and infant exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Infant age, prematurity, dose, polypharmacy, maternal response, and clinical outcomes matter; low transfer is not zero risk.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006

Linked sources

LactMed synthesisEXT-047 · Not formally appraised
Drugs and Lactation Database (LactMed)D-LACTMED · Dynamic · Current peer-reviewed database

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-068
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-069Module A

Provisional public source

Venlafaxine's active metabolite can be measurable in nursing infants, duloxetine/desvenlafaxine transfer appears modest or low in small studies, and levomilnacipran/milnacipran evidence is sparse.

LactMed synthesislactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate by agent; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate by agent; not GRADE
Comparator: between-agent milk and infant exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Small samples and limited newborn/long-term outcomes; class analogy is especially weak for levomilnacipran.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

LactMed synthesisEXT-048 · Not formally appraised
Drugs and Lactation Database (LactMed)D-LACTMED · Dynamic · Current peer-reviewed database

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-069
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-070Module A

Provisional public source

Routine pre-delivery taper of an effective antidepressant to prevent neonatal adaptation is not recommended; it may precipitate relapse and does not eliminate exposure.

guideline-linked clinical positionlate pregnancy and deliveryStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: guideline-consistent position; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline-consistent position; not GRADE
Comparator: continuation versus routine taper
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Direct randomized taper evidence is limited; individual toxicity or patient preference can still justify a supervised change.

Public-source disposition — not a commissioned recommendation

include

Open sources, mapped records, and appraisal controls

Mapped medication records

FluoxetineMED-001
SertralineMED-002
CitalopramMED-003
EscitalopramMED-004
ParoxetineMED-005
FluvoxamineMED-006
VenlafaxineMED-007
DesvenlafaxineMED-008
DuloxetineMED-009
LevomilnacipranMED-010
MilnacipranMED-011
BupropionMED-012
MirtazapineMED-013
TrazodoneMED-014
NefazodoneMED-015
VilazodoneMED-016
VortioxetineMED-017
Gepirone extended-releaseMED-018
Dextromethorphan hydrobromide/bupropion hydrochlorideMED-019
AgomelatineMED-020
TianeptineMED-021
ReboxetineMED-022
MianserinMED-023
OpipramolMED-024
AmitriptylineMED-025
NortriptylineMED-026
ImipramineMED-027
DesipramineMED-028
ClomipramineMED-029
Doxepin (antidepressant-dose oral)MED-030
Doxepin (low-dose insomnia)MED-031
TrimipramineMED-032
ProtriptylineMED-033
AmoxapineMED-034
MaprotilineMED-035
DosulepinMED-036
LofepramineMED-037

Linked sources

guideline position; class evidence synthesis; guideline-linked clinical positionEXT-001 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: 37486661
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-070
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-071Module A

Provisional public source

Psychiatric liothyronine augmentation lacks a systematic pregnancy cohort; a case report illustrates suppression of maternal T4, while thyroid guidance prefers levothyroxine rather than T3-containing treatment for hypothyroidism in pregnancy.

case report and specialty guidancepregnancyClinical-position linkage pending

Public-source certainty descriptor: very low for psychiatric reproductive outcomes; high for need to monitor thyroid physiology; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for psychiatric reproductive outcomes; high for need to monitor thyroid physiology; not GRADE
Comparator: no comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

One published psychiatric-augmentation pregnancy case; no reliable cohort estimate.

Limitations

Single case cannot quantify fetal risk; replacement and psychiatric augmentation are different indications; thyroid guidance addresses hypothyroidism, not antidepressant efficacy.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

LiothyronineMED-051

Linked sources

case report and specialty guidanceEXT-049 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-609C6ACD42EE · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-071
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-072Module A

Evidence gap

Pramipexole pregnancy evidence is limited to small Parkinson disease or restless-legs series and case reports; no breastfeeding-use data were identified and prolactin suppression may interfere with milk production.

small prospective series and LactMed synthesispregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate psychiatric comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate; available pregnancy series are underpowered.

Limitations

Nonpsychiatric indications, small selected samples, no power for rare outcomes, and no milk/infant concentration or outcome data.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

PramipexoleMED-052

Linked sources

small prospective series and LactMed synthesisEXT-050 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-DD53F9594D5C · Unverified metadata

Citation controls

PMID: 23083216
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-072
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-073Module A

Evidence gap

High-dose L-methylfolate used as a depression medical food is not equivalent to routine prenatal folic acid; NIH ODS states that 5-MTHF has not been tested for neural-tube-defect prevention and folic acid is the only form currently proven for that outcome.

public-health guidance and evidence gappreconception and pregnancySwitch before conception

Public-source certainty descriptor: high for folic-acid prevention guidance; insufficient for psychiatric-dose L-methylfolate safety/efficacy; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for folic-acid prevention guidance; insufficient for psychiatric-dose L-methylfolate safety/efficacy; not GRADE
Comparator: 5-MTHF evidence versus established folic-acid prevention evidence
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Folic acid guidance 400-800 mcg/day for most capable-of-pregnancy individuals; no reliable psychiatric-dose L-methylfolate reproductive estimate.

Limitations

Does not imply L-methylfolate is teratogenic; total folate dose, B12 status, product composition, and high-risk NTD recommendations vary.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

L-methylfolate (prescription medical food)MED-054

Linked sources

public-health guidance and evidence gapEXT-051 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-073
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-074Module A

Evidence gap

NCCIH concludes that SAMe pregnancy and long-term safety data are too limited for conclusions; serotonergic interactions and bipolar activation are clinically relevant.

authoritative evidence gappregnancy and lactationDelivery/postpartum/lactation

Public-source certainty descriptor: insufficient evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: insufficient evidence; not GRADE
Comparator: no adequate comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable quantitative estimate.

Limitations

Supplement formulation and purity vary; nonpregnant trials are short and do not establish perinatal benefit or safety.

Public-source disposition — not a commissioned recommendation

include_as_gap

Open sources, mapped records, and appraisal controls

Mapped medication records

S-adenosyl-L-methionineMED-055

Linked sources

authoritative evidence gapEXT-052 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-074
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-075Module A

Provisional public source

Lorazepam injection shares lorazepam's benzodiazepine reproductive profile but adds rapid parenteral sedation, respiratory-depression, opioid-interaction, monitored-use, and formulation-excipient considerations; a necessary status-epilepticus or procedural dose should not be withheld solely because of pregnancy.

regulatory label and route-specific positionacute pregnancy treatment, delivery, and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: high for acute respiratory and interaction hazards; insufficient route-specific reproductive evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for acute respiratory and interaction hazards; insufficient route-specific reproductive evidence; not GRADE
Comparator: parenteral versus oral exposure; no reproductive comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable reproductive effect estimate for the injection route.

Limitations

Older label; route-specific pregnancy cohorts absent; repeated/near-delivery exposure differs from one monitored emergency dose.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Lorazepam injectionMED-139
LorazepamMED-169

Linked sources

regulatory label and route-specific positionEXT-053 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-190E7E54B347 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-075
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-076Module A

Provisional public source

Diphenhydramine injection shares the active-moiety pregnancy/lactation profile of oral diphenhydramine, while parenteral use adds rapid anticholinergic and sedative effects; necessary acute allergy or extrapyramidal-symptom treatment should not be withheld solely because of pregnancy.

regulatory label and route-specific positionacute pregnancy treatment, delivery, and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate for no large active-moiety malformation effect; insufficient route-specific evidence; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate for no large active-moiety malformation effect; insufficient route-specific evidence; not GRADE
Comparator: parenteral versus oral exposure; no reproductive comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable reproductive effect estimate for the injection route.

Limitations

Indication, dose, co-sedatives, and rapid administration affect maternal risk; route-specific fetal and infant outcome cohorts are absent.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Diphenhydramine injectionMED-140
DiphenhydramineMED-206

Linked sources

regulatory label and route-specific positionEXT-054 · Not formally appraised
class evidence synthesisEXT-033 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-076
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-077Module A

Provisional public source

A separate case-control study reported a VSD signal with first-trimester bupropion, while other cardiac-defect estimates were not elevated.

case-control studyfirst trimesterUnplanned exposure

Public-source certainty descriptor: low for an organ-specific signal; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for an organ-specific signal; not GRADE
Comparator: no bupropion exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Any bupropion exposure and VSD adjusted OR 1.6 (95% CI 1.0–2.8); bupropion alone adjusted OR 2.5 (1.3–5.0).

Limitations

Small exposed counts, recall/exposure limitations, multiple comparisons, and nonreplication; do not present as established causation.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

BupropionMED-012

Linked sources

case-control studyEXT-055 · Not formally appraised

Citation controls

PMID: 24920293
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-077
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

A-078Module A

Provisional public source

A four-participant lactation pharmacokinetic study found low ketamine and norketamine relative infant doses during a short treatment series.

lactation pharmacokinetic studypostpartum short-course dosingStable continuationDelivery/postpartum/lactation

Public-source certainty descriptor: low for infant safety; moderate for measured transfer under studied conditions; not GRADE
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low for infant safety; moderate for measured transfer under studied conditions; not GRADE
Comparator: no unexposed infant comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Ketamine RID 0.34%–0.57%; norketamine RID 0.29%–0.95%.

Limitations

Four participants; limited infant ingestion/outcomes; cannot support repeated maintenance treatment or long-term neurodevelopment.

Public-source disposition — not a commissioned recommendation

include_with_caution

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactation pharmacokinetic studyEXT-056 · Not formally appraised

Citation controls

PMID: 37683228
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-078
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-001Module B

Provisional public source

First-trimester lithium exposure was associated with a modestly increased cardiac-malformation risk in a large adjusted US cohort.

risk estimatefirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate—large observational cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—large observational cohort
Comparator: no lithium exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Cardiac malformations: 16/663 lithium-exposed infants (2.41%) versus 15,251/1,322,955 unexposed infants (1.15%); adjusted RR 1.65 (95% CI 1.02–2.68). The crude absolute difference is about 1.26 percentage points and is not a causal NNH.

Limitations

Residual confounding, prescription-fill exposure, and low counts for specific cardiac defects.

Public-source disposition — not a commissioned recommendation

Do not portray lithium as either harmless or absolutely contraindicated; offer detailed second-trimester cardiac/anatomy ultrasound.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057

Linked sources

risk estimate; dose-responseEXT-057 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-079
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-002Module B

Provisional public source

The lithium cardiac-malformation association was dose related in the primary cohort.

dose-responsefirst trimesterUnplanned exposure

Public-source certainty descriptor: low-to-moderate—observational dose strata
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—observational dose strata
Comparator: no lithium exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

RR 1.11 at ≤600 mg/day; 1.60 at 601–900 mg/day; 3.22 at >900 mg/day

Limitations

Wide confidence intervals, prescribed rather than ingested dose, and possible severity confounding.

Public-source disposition — not a commissioned recommendation

Use the lowest dose that maintains stability; do not reduce below the effective dose solely to reach a nominal threshold.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057

Linked sources

risk estimate; dose-responseEXT-057 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-080
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-003Module B

Provisional public source

Lithium clearance rises during pregnancy and falls rapidly after birth, requiring concentration-guided pregnancy and postpartum management.

pharmacokineticspregnancy through early postpartumStable continuationDelivery/postpartum/lactation

Public-source certainty descriptor: moderate for direction; low for exact schedule
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for direction; low for exact schedule
Comparator: prepregnancy personal baseline
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Personal trough monitoring; observational authors proposed weekly checks from 34 weeks and twice weekly for the first 2 postpartum weeks

Limitations

Exact monitoring schedule is not trial validated and must respond to renal function, illness, and interactions.

Public-source disposition — not a commissioned recommendation

Record a stable baseline, intensify checks late pregnancy/early postpartum, and reverse pregnancy dose increases promptly.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057

Linked sources

pharmacokineticsEXT-058 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-081
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-004Module B

Provisional public source

Routine lithium dose reduction or discontinuation before delivery is controversial rather than settled.

clinical controversylabor and deliveryStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low—small nonrandomized study
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—small nonrandomized study
Comparator: lowered/held versus continued exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Small observational cohort found no neonatal-outcome association with delivery lithium concentration and recommended against routine lowering

Limitations

Small sample, nonrandomized management, and limited power for rare toxicity; ACOG notes some experts still hold before labor/scheduled delivery.

Public-source disposition — not a commissioned recommendation

Individualize using relapse risk, renal/fluid status, scheduled versus spontaneous delivery, and neonatal monitoring capacity.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057

Linked sources

clinical controversyEXT-059 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-082
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-005Module B

Provisional public source

Breastfeeding during lithium treatment is a conditional, monitoring-intensive option because infant exposure is highly variable.

lactationlactation, especially newborn periodUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low—case series and pharmacokinetic reports
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—case series and pharmacokinetic reports
Comparator: no breast-milk lithium exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single reliable relative infant dose; maternal milk and infant serum vary widely

Limitations

Selection of healthy term infants and heterogeneous infant lithium/renal/thyroid monitoring.

Public-source disposition — not a commissioned recommendation

Use only with coordinated infant clinical and laboratory monitoring; avoid or reconsider during prematurity, dehydration, infection, or renal impairment.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057

Linked sources

lactationEXT-060 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-083
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-006Module B

Provisional public source

Valproate has the highest major-congenital-malformation prevalence among commonly studied antiseizure monotherapies across the cited evidence sets.

risk estimatefirst-trimester monotherapySwitch before conception

Public-source certainty descriptor: high for an association; observational registry evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for an association; observational registry evidence
Comparator: other studied ASM monotherapies/background prevalence about 2.4–2.9%
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

AAN/AES/SMFM synthesis: MCM prevalence approximately 9.7%; EURAP 2024: 9.9% (153/1,549; 95% CI 8.5–11.5).

Limitations

Dose, indication, registry methods, and live-birth selection affect absolute prevalence.

Public-source disposition — not a commissioned recommendation

Avoid valproate when a clinically effective alternative exists.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-084
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-007Module B

Provisional public source

Valproate is associated with neural-tube defects and other organ-specific malformations.

risk estimatefirst trimester/periconceptionSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: high for direction; moderate for exact prevalence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: high for direction; moderate for exact prevalence
Comparator: no valproate or lower-risk ASM
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

AAN/AES/SMFM synthesis: neural-tube-defect prevalence approximately 1.4%, urogenital approximately 1.2%, and renal approximately 1.4%.

Limitations

Registry heterogeneity and dose/polytherapy differences.

Public-source disposition — not a commissioned recommendation

Prioritize preconception substitution and detailed fetal assessment after exposure; folate does not erase risk.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-085
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-008Module B

Provisional public source

Prenatal valproate exposure is associated with lower cognitive scores and increased neurodevelopmental-disorder risk relative to several alternatives.

neurodevelopmentthroughout pregnancySwitch before conceptionUnplanned exposure

Public-source certainty descriptor: moderate—consistent observational evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—consistent observational evidence
Comparator: other ASMs or unexposed children
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Directionally lower IQ and higher autism-spectrum/neurodevelopmental risk; no single pooled effect used here

Limitations

Confounding by indication, dose, polytherapy, parental factors, and outcome ascertainment.

Public-source disposition — not a commissioned recommendation

Avoid antenatal valproate where feasible and ensure developmental surveillance after exposure.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised
Valproate reproductive risks hubR-MHRA-VAL · Updated 2025-06-10 · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-086
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-009Module B

Provisional public source

The current US divalproex label contraindicates migraine prophylaxis in pregnancy and in women of childbearing potential not using effective contraception.

regulatory restrictionpreconception and pregnancyNew initiationSwitch before conception

Public-source certainty descriptor: regulatory label
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory label
Comparator: alternative therapy
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Contraindication for migraine prevention; epilepsy/bipolar use only when alternatives fail or are unacceptable

Limitations

US labeling; other jurisdictions apply different or stricter controls.

Public-source disposition — not a commissioned recommendation

Do not initiate for migraine prevention in pregnancy; use for epilepsy/bipolar disorder only under exceptional specialist rationale.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

regulatory restrictionEXT-063 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-087
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-010Module B

Provisional public source

UK valproate controls include a pregnancy-prevention programme and two-specialist agreement for initiation under age 55 under current materials.

regulatory restrictionpreconception and ongoing prescribingNew initiationSwitch before conception

Public-source certainty descriptor: current regulator requirement
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: current regulator requirement
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Pregnancy-prevention programme for women/girls able to become pregnant; two specialists for new initiation under 55 with defined exceptions

Limitations

Jurisdiction-specific rules and exceptions; requirements can change.

Public-source disposition — not a commissioned recommendation

Verify current local forms, specialist approvals, contraception, and annual review before prescribing.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

regulatory restrictionEXT-064 · Not formally appraised
Valproate reproductive risks hubR-MHRA-VAL · Updated 2025-06-10 · Current
Valproate two-specialist review clarificationR-MHRA-VAL-CLAR · 2025-02-13 · Current clarification

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-088
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-011Module B

Provisional public source

Carbamazepine monotherapy is associated with higher malformation prevalence than the lower-risk lamotrigine, levetiracetam, and oxcarbazepine options.

comparative riskfirst trimesterClinical-position linkage pending

Public-source certainty descriptor: moderate—registry evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—registry evidence
Comparator: lower-risk ASM monotherapies
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MHRA review: overall MCM prevalence approximately 4–5%; EURAP 2024: 5.4% (121/2,255; 95% CI 4.5–6.4).

Limitations

Dose, seizure type, polytherapy, and registry methods vary.

Public-source disposition — not a commissioned recommendation

Prefer a lower-risk effective ASM when appropriate; do not abruptly replace effective therapy after conception.

Open sources, mapped records, and appraisal controls

Mapped medication records

CarbamazepineMED-061

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-089
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-012Module B

Provisional public source

Lamotrigine is among the lower-MCM monotherapy options in the cited 2024 evidence sets.

risk estimatefirst-trimester monotherapyClinical-position linkage pending

Public-source certainty descriptor: moderate-to-high—large registry synthesis
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate-to-high—large registry synthesis
Comparator: other ASM monotherapies/background prevalence
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

AAN/AES/SMFM synthesis: approximately 3.1%; EURAP 2024: 3.1% (110/3,584; 95% CI 2.5–3.7).

Limitations

Not zero risk; dose-specific and psychiatric-indication data are less certain.

Public-source disposition — not a commissioned recommendation

Prefer when clinically appropriate and effective for the indication.

Open sources, mapped records, and appraisal controls

Mapped medication records

LamotrigineMED-062

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-090
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-013Module B

Provisional public source

Lamotrigine clearance can rise markedly in pregnancy and dose-normalized concentrations commonly fall.

pharmacokineticspregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: moderate—prospective PK cohorts
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—prospective PK cohorts
Comparator: prepregnancy or postpartum concentration
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

ACOG cites clearance increases up to 330%; MONEAD estimated dose-normalized concentrations up to 56.1% lower than postpartum

Limitations

Very high interindividual variability; postpartum is an imperfect prepregnancy comparator.

Public-source disposition — not a commissioned recommendation

Use a personal baseline and clinical response/seizure control to guide serial levels and dose changes.

Open sources, mapped records, and appraisal controls

Mapped medication records

LamotrigineMED-062

Linked sources

pharmacokineticsEXT-065 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-091
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-014Module B

Provisional public source

Pregnancy-escalated lamotrigine doses require planned postpartum reduction because concentrations can rise within days after birth.

postpartum managementfirst postpartum days to weeksDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate—prospective cohort with small taper comparison
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—prospective cohort with small taper comparison
Comparator: no planned taper
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Maternal toxicity can appear by postpartum day 3; empiric taper reduced toxicity in a small cohort

Limitations

No universal taper schedule; dose changes must preserve seizure/mood control.

Public-source disposition — not a commissioned recommendation

Write the postpartum taper before delivery and review symptoms/level early after birth.

Open sources, mapped records, and appraisal controls

Mapped medication records

LamotrigineMED-062

Linked sources

postpartum managementEXT-066 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-092
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-015Module B

Provisional public source

Oxcarbazepine is among lower-MCM monotherapies when clinically appropriate.

risk estimatefirst-trimester monotherapyUnplanned exposure

Public-source certainty descriptor: moderate—registry synthesis
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—registry synthesis
Comparator: other ASM monotherapies/background prevalence
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

AAN/AES/SMFM synthesis: approximately 3.1%; EURAP 2024: 2.9% (13/443; 95% CI 1.7–5.0).

Limitations

Smaller exposure base and limited psychiatric/neurodevelopmental data.

Public-source disposition — not a commissioned recommendation

Consider for a compatible seizure syndrome; do not imply established bipolar efficacy.

Open sources, mapped records, and appraisal controls

Mapped medication records

OxcarbazepineMED-063

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-093
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-016Module B

Provisional public source

Oxcarbazepine and active-metabolite dose-normalized concentrations fall during pregnancy.

pharmacokineticspregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: moderate—prospective PK cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—prospective PK cohort
Comparator: postpartum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MONEAD: oxcarbazepine 32.6% lower; unbound active metabolite 30.6% lower versus postpartum

Limitations

Population average does not define an individual dose change.

Public-source disposition — not a commissioned recommendation

Follow the active metabolite, sodium, and clinical control; reassess pregnancy increases postpartum.

Open sources, mapped records, and appraisal controls

Mapped medication records

OxcarbazepineMED-063

Linked sources

pharmacokineticsEXT-065 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-094
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-017Module B

Provisional public source

Topiramate monotherapy is associated with an increased oral-cleft risk.

risk estimatefirst trimesterClinical-position linkage pending

Public-source certainty descriptor: moderate-to-high—consistent registry evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate-to-high—consistent registry evidence
Comparator: no topiramate/lower-risk ASM
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Oral-cleft prevalence approximately 1.4% in the guideline synthesis

Limitations

Dose, indication, and co-medication vary; prevalence is not an adjusted causal effect.

Public-source disposition — not a commissioned recommendation

Avoid when feasible, especially for nonessential/off-label indications.

Open sources, mapped records, and appraisal controls

Mapped medication records

TopiramateMED-064

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised
Topiramate: introduction of new safety measures including a pregnancy-prevention programmeR-MHRA-TOP24 · 2024-06-20 · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-095
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-018Module B

Provisional public source

Topiramate is associated with fetal growth restriction/small-for-gestational-age birth.

obstetric riskpregnancyStable continuationSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: moderate—observational registry evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—observational registry evidence
Comparator: women with epilepsy taking no antiseizure medicine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MHRA communicates about 18 SGA infants per 100 exposed versus 5 per 100 women with epilepsy taking no ASM

Limitations

Regulatory summary; confounding by epilepsy, dose, smoking, and co-medications.

Public-source disposition — not a commissioned recommendation

Avoid when alternatives fit and arrange serial growth assessment after continued exposure.

Open sources, mapped records, and appraisal controls

Mapped medication records

TopiramateMED-064

Linked sources

obstetric risk; regulatory restrictionEXT-067 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised
Topiramate: introduction of new safety measures including a pregnancy-prevention programmeR-MHRA-TOP24 · 2024-06-20 · Current
UK/MHRA · topiramateSUR-04 · 2024-06-20 · No

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-096
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-019Module B

Provisional public source

Current UK measures contraindicate topiramate in pregnancy for migraine prevention and restrict epilepsy use to cases with no suitable alternative.

regulatory restrictionpreconception and pregnancyNew initiationSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: current regulator requirement
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: current regulator requirement
Comparator: alternative therapy
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Pregnancy-prevention programme with pregnancy testing and highly effective contraception for women of childbearing potential

Limitations

UK-specific; local requirements must be checked elsewhere.

Public-source disposition — not a commissioned recommendation

Do not initiate for migraine prevention in pregnancy; urgently review any unplanned pregnancy without abruptly stopping epilepsy treatment.

Open sources, mapped records, and appraisal controls

Mapped medication records

TopiramateMED-064

Linked sources

obstetric risk; regulatory restrictionEXT-067 · Not formally appraised
Topiramate: introduction of new safety measures including a pregnancy-prevention programmeR-MHRA-TOP24 · 2024-06-20 · Current
UK/MHRA · topiramateSUR-04 · 2024-06-20 · No

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-097
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-020Module B

Provisional public source

Early gabapentin exposure was not associated with a clear overall major-malformation increase, but a cardiac signal could not be excluded.

risk estimatefirst trimesterSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: moderate—large claims cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—large claims cohort
Comparator: unexposed pregnancies
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No clear overall MCM association after adjustment; imprecise cardiac concern

Limitations

Prescription fills, residual confounding by pain/epilepsy/opioids, and outcome misclassification.

Public-source disposition — not a commissioned recommendation

Do not label as proven teratogen; use only for a material indication and prefer data-rich alternatives when equal.

Open sources, mapped records, and appraisal controls

Mapped medication records

GabapentinMED-065

Linked sources

risk estimate; obstetric riskEXT-068 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-098
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-021Module B

Provisional public source

Late or sustained gabapentin exposure was associated with preterm birth, SGA, and NICU admission.

obstetric risklate pregnancy or exposure throughout pregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate—observational claims cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—observational claims cohort
Comparator: unexposed pregnancies
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Directionally increased PTB, SGA, and NICU outcomes in adjusted analyses

Limitations

Strong potential for confounding by indication, opioid use, smoking, and illness severity.

Public-source disposition — not a commissioned recommendation

Reassess chronic late exposure and co-sedatives; plan neonatal respiratory/feeding observation.

Open sources, mapped records, and appraisal controls

Mapped medication records

GabapentinMED-065

Linked sources

risk estimate; obstetric riskEXT-068 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-099
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-022Module B

Provisional public source

Pregabalin data are compatible with no increase and with a small MCM increase; a large Nordic estimate was not statistically significant.

risk estimatefirst trimesterClinical-position linkage pending

Public-source certainty descriptor: low-to-moderate—observational cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—observational cohort
Comparator: unexposed pregnancies
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MCM 5.9% versus 4.1%; adjusted prevalence ratio 1.14 (95% CI 0.96–1.35)

Limitations

Confidence interval includes no association; confounding by pain, anxiety, epilepsy, and co-medications.

Public-source disposition — not a commissioned recommendation

Use cautiously for a clear benefit; avoid describing the risk as either established or excluded.

Open sources, mapped records, and appraisal controls

Mapped medication records

PregabalinMED-066

Linked sources

risk estimateEXT-069 · Not formally appraised
Pregabalin: findings of safety study on risks during pregnancyR-MHRA-PGB22 · 2022-04-19 · Current safety communication

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-100
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-023Module B

Provisional public source

Levetiracetam is among lower-MCM monotherapies in the cited 2024 evidence sets.

risk estimatefirst-trimester monotherapyClinical-position linkage pending

Public-source certainty descriptor: moderate-to-high—large registry synthesis
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate-to-high—large registry synthesis
Comparator: other ASM monotherapies/background prevalence
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

AAN/AES/SMFM synthesis: approximately 3.5%; EURAP 2024: 2.5% (33/1,325; 95% CI 1.8–3.5).

Limitations

Not zero risk; neurodevelopmental and very-high-dose data are less extensive.

Public-source disposition — not a commissioned recommendation

Prefer when clinically appropriate for the seizure syndrome.

Open sources, mapped records, and appraisal controls

Mapped medication records

LevetiracetamMED-067

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-101
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-024Module B

Provisional public source

Levetiracetam dose-normalized concentrations commonly fall in pregnancy.

pharmacokineticspregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: moderate—prospective PK cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—prospective PK cohort
Comparator: postpartum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MONEAD: 36.8% lower during pregnancy versus postpartum

Limitations

Average effect masks individual variability.

Public-source disposition — not a commissioned recommendation

Use a personal trough and seizure control to guide dose; reverse increases after birth.

Open sources, mapped records, and appraisal controls

Mapped medication records

LevetiracetamMED-067

Linked sources

pharmacokineticsEXT-065 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-102
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-025Module B

Evidence gap

Zonisamide pregnancy evidence is too sparse for a reliable malformation estimate, with a possible low-birth-weight signal.

evidence gappregnancyStable continuation

Public-source certainty descriptor: very low—small registry series
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—small registry series
Comparator: unexposed or other ASM
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Small UK/Ireland register; no stable comparative effect

Limitations

Small numbers, polytherapy, selection bias, and imprecision.

Public-source disposition — not a commissioned recommendation

Prefer a better-studied effective ASM; if continued, add fetal-growth and level monitoring.

Open sources, mapped records, and appraisal controls

Mapped medication records

ZonisamideMED-068

Linked sources

evidence gapEXT-070 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: 34273670
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-103
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-026Module B

Evidence gap

Tiagabine has insufficient controlled human pregnancy data for malformation, obstetric, neonatal, or neurodevelopmental risk estimation.

evidence gapany pregnancy exposureNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low
Comparator: not estimable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable rate

Limitations

Tiny exposed denominator and lack of comparative cohorts.

Public-source disposition — not a commissioned recommendation

Avoid first-line initiation when a data-rich effective ASM exists; do not abruptly stop established therapy.

Open sources, mapped records, and appraisal controls

Mapped medication records

TiagabineMED-069

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-104
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-027Module B

Provisional public source

Prospective lacosamide pharmacovigilance outcomes are preliminary and do not establish comparative safety.

descriptive pregnancy outcomespregnancySwitch before conception

Public-source certainty descriptor: very low—uncontrolled pharmacovigilance
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—uncontrolled pharmacovigilance
Comparator: none
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Congenital malformations 1/44 (2.3%) monotherapy and 11/160 (6.9%) polytherapy

Limitations

Small counts, reporting bias, no unexposed comparator, and confounding by polytherapy/severity.

Public-source disposition — not a commissioned recommendation

Do not interpret 2.3% as proof of low risk; prefer data-rich alternatives if clinically equivalent.

Open sources, mapped records, and appraisal controls

Mapped medication records

LacosamideMED-070

Linked sources

descriptive pregnancy outcomesEXT-071 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: 38411300
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-105
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-028Module B

Provisional public source

Lacosamide dose-normalized concentrations fall in pregnancy.

pharmacokineticspregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate—small prospective PK sample
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—small prospective PK sample
Comparator: postpartum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MONEAD: 39.9% lower during pregnancy versus postpartum

Limitations

Limited lacosamide sample and no validated population target.

Public-source disposition — not a commissioned recommendation

Use personal baseline/clinical control; reassess increased dose postpartum.

Open sources, mapped records, and appraisal controls

Mapped medication records

LacosamideMED-070

Linked sources

pharmacokineticsEXT-065 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-106
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-029Module B

Provisional public source

Phenytoin is associated with a higher MCM prevalence and fetal hydantoin-pattern anomalies.

risk estimatefirst trimesterStable continuation

Public-source certainty descriptor: moderate—historical and registry evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—historical and registry evidence
Comparator: lower-risk ASM monotherapy/background
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

MHRA review: overall MCM prevalence approximately 6%; EURAP 2024: 6.3% (9/142; 95% CI 3.4–11.6).

Limitations

Older studies, polytherapy, dose differences, and changing ascertainment.

Public-source disposition — not a commissioned recommendation

Prefer a lower-risk effective ASM when feasible; use free/adjusted levels if continued.

Open sources, mapped records, and appraisal controls

Mapped medication records

PhenytoinMED-071

Linked sources

risk estimate; comparative riskEXT-061 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-58092F565A9B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-107
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-030Module B

Provisional public source

Phenobarbital exposure is associated with cardiac malformations and oral clefts.

risk estimatefirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate—registry synthesis
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—registry synthesis
Comparator: no phenobarbital/lower-risk ASM
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Cardiac-malformation prevalence approximately 4.4%; oral-cleft prevalence approximately 2.2%

Limitations

Historical use, dose/polytherapy differences, and imprecise defect-specific estimates.

Public-source disposition — not a commissioned recommendation

Avoid when an effective lower-risk ASM exists; do not abruptly withdraw chronic barbiturate therapy.

Open sources, mapped records, and appraisal controls

Mapped medication records

PhenobarbitalMED-072

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-108
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-031Module B

Provisional public source

Once pregnancy is established, replacing an effective antiseizure medicine requires caution because seizure recurrence can harm the pregnant patient and fetus.

guideline recommendationafter conceptionStable continuationSwitch before conception

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: continuing effective therapy
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single effect estimate; AAN/AES/SMFM caution

Limitations

Decision varies by seizure syndrome, prior control, dose, and drug-specific fetal risk.

Public-source disposition — not a commissioned recommendation

Use urgent specialist shared decision-making; never perform an abrupt unsupervised switch.

Open sources, mapped records, and appraisal controls

Mapped medication records

Valproic acidMED-058
Divalproex sodiumMED-059
Valproate sodiumMED-060
CarbamazepineMED-061
LamotrigineMED-062
OxcarbazepineMED-063
TopiramateMED-064
GabapentinMED-065
PregabalinMED-066
LevetiracetamMED-067
ZonisamideMED-068
TiagabineMED-069
LacosamideMED-070
PhenytoinMED-071
PhenobarbitalMED-072

Linked sources

neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-109
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-032Module B

Provisional public source

ACOG recommends against discontinuing mood stabilizers during pregnancy solely because of pregnancy, except that valproate should be avoided when possible.

guideline recommendationpregnancyStable continuationSwitch before conception

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: discontinuation
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Strong recommendation; moderate-quality evidence in ACOG for continuation except valproate

Limitations

Not a mandate to continue every ineffective or unsafe regimen; indication and relapse history remain decisive.

Public-source disposition — not a commissioned recommendation

Continue effective non-valproate treatment in most stable patients; prioritize planned valproate substitution.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-110
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-033Module B

Provisional public source

Large adjusted cohorts do not show a meaningful overall increase in major congenital malformations for antipsychotics as a class.

class risk estimatefirst trimesterUnplanned exposure

Public-source certainty descriptor: moderate—large adjusted cohorts
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—large adjusted cohorts
Comparator: no antipsychotic exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Huybrechts: atypical adjusted RR 1.05 (95% CI 0.96–1.16); typical adjusted RR 0.90 (0.62–1.31)

Limitations

Contextual class evidence only; do not treat the class point estimates as drug-, route-, fixed-combination-, emergency-formulation-, or LAI-specific estimates. Class averages can hide rare drug-specific effects; confounding, live-birth selection, and exposure misclassification remain.

Public-source disposition — not a commissioned recommendation

Do not stop an effective antipsychotic solely because of a presumed class teratogenic effect.

Open sources, mapped records, and appraisal controls

Mapped medication records

ChlorpromazineMED-073
FluphenazineMED-074
HaloperidolMED-075
PerphenazineMED-076
TrifluoperazineMED-077
ThiothixeneMED-078
Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
ClozapineMED-097
RisperidoneMED-098
PaliperidoneMED-099
OlanzapineMED-100
QuetiapineMED-101
ZiprasidoneMED-102
AripiprazoleMED-103
Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138
Quetiapine extended-releaseMED-053

Linked sources

class risk estimate; drug-specific signalEXT-073 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-111
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-034Module B

Provisional public source

A small risperidone malformation signal in one large cohort requires confirmation.

drug-specific signalfirst trimesterStable continuationNew initiationSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: low—single adjusted signal not consistently replicated
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—single adjusted signal not consistently replicated
Comparator: no antipsychotic exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted RR 1.26 (95% CI 1.02–1.56)

Limitations

Multiple comparisons, possible residual confounding, no consistent defect pattern, and no LAI-specific estimate.

Public-source disposition — not a commissioned recommendation

Discuss uncertainty without forced switching in a stable responder; consider alternatives for new starts when equally effective.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

class risk estimate; drug-specific signalEXT-073 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-112
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-035Module B

Provisional public source

An olanzapine–oral-cleft association in a Nordic/US study was unstable and hypothesis generating.

drug-specific signalfirst trimesterStable continuationSwitch before conceptionUnplanned exposure

Public-source certainty descriptor: low—rare outcome and inconsistent sensitivity analyses
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—rare outcome and inconsistent sensitivity analyses
Comparator: no antipsychotic exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted RR approximately 2.1 (95% CI 1.1–4.3), attenuated/unstable in sensitivity analyses

Limitations

Rare event, multiple comparisons, residual confounding, and no formulation-specific estimate.

Public-source disposition — not a commissioned recommendation

Do not call causal or mandate switching; use routine detailed anatomy assessment and standard counseling.

Open sources, mapped records, and appraisal controls

Mapped medication records

OlanzapineMED-100
Olanzapine pamoateMED-126
Olanzapine short-acting intramuscularMED-136

Linked sources

drug-specific signal; evidence gap; route/formulation principleEXT-074 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-113
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-036Module B

Provisional public source

Clozapine, olanzapine, and quetiapine as a high-metabolic-risk group were associated with gestational diabetes and large-for-gestational-age birth.

obstetric riskpregnancyStable continuation

Public-source certainty descriptor: moderate for group association; low for individual drugs
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate for group association; low for individual drugs
Comparator: untreated women or prepregnancy discontinuers
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Adjusted GDM RR 1.8 (95% CI 1.3–2.4) versus untreated pregnancies and 1.6 (1.2–2.1) versus prepregnancy discontinuers; adjusted LGA RR 1.6 (1.3–1.9) and 1.3 (1.1–1.6), respectively.

Limitations

The high-metabolic-risk group combined clozapine, olanzapine, and quetiapine and could not separate agents; BMI and measured maternal factors were adjusted, but residual confounding and differential surveillance remain.

Public-source disposition — not a commissioned recommendation

Continue needed treatment with proactive weight/glucose care and standard prenatal GDM screening.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

obstetric riskEXT-075 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-114
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-037Module B

Provisional public source

ACOG recommends gestational-diabetes screening for pregnant patients using antipsychotics consistent with standard prenatal care.

guideline recommendationpregnancyUnplanned exposure

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: standard prenatal care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No special early-screening effect estimate established

Limitations

Evidence linking exposure to GDM is heterogeneous and confounded.

Public-source disposition — not a commissioned recommendation

Ensure standard GDM screening and individualize any additional metabolic surveillance.

Open sources, mapped records, and appraisal controls

Mapped medication records

ChlorpromazineMED-073
FluphenazineMED-074
HaloperidolMED-075
PerphenazineMED-076
TrifluoperazineMED-077
ThiothixeneMED-078
Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
ClozapineMED-097
RisperidoneMED-098
PaliperidoneMED-099
OlanzapineMED-100
QuetiapineMED-101
ZiprasidoneMED-102
AripiprazoleMED-103
Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138
Quetiapine extended-releaseMED-053

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-115
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-038Module B

Provisional public source

Neonatal EPS or withdrawal/adaptation signs have been reported after third-trimester antipsychotic exposure.

neonatal safetythird trimester/near deliveryUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: regulatory class warning; absolute risk unknown
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory class warning; absolute risk unknown
Comparator: no late antipsychotic exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Reported signs include agitation, hypertonia or hypotonia, tremor, somnolence, respiratory distress, and feeding disorder; severity and duration vary, and no reliable incidence is available.

Limitations

Spontaneous reports, co-medications, illness severity, and no reliable denominator; Cobenfy is mechanistically distinct and excluded from this class claim.

Public-source disposition — not a commissioned recommendation

Do not routinely taper a necessary drug; notify neonatal clinicians and observe symptoms after late exposure.

Open sources, mapped records, and appraisal controls

Mapped medication records

ChlorpromazineMED-073
FluphenazineMED-074
HaloperidolMED-075
PerphenazineMED-076
TrifluoperazineMED-077
ThiothixeneMED-078
Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
ClozapineMED-097
RisperidoneMED-098
PaliperidoneMED-099
OlanzapineMED-100
QuetiapineMED-101
ZiprasidoneMED-102
AripiprazoleMED-103
AsenapineMED-104
IloperidoneMED-105
LurasidoneMED-106
BrexpiprazoleMED-107
CariprazineMED-108
LumateperoneMED-109
PimavanserinMED-110
MilsaperidoneMED-112
Olanzapine/fluoxetineMED-113
Olanzapine/samidorphanMED-114
Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138
Quetiapine extended-releaseMED-053

Linked sources

neonatal safetyEXT-076 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-116
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-039Module B

Provisional public source

In two large US claims cohorts, the apparent association between second-half-pregnancy antipsychotic exposure and childhood neurodevelopmental disorders attenuated substantially after confounding adjustment; individual-drug analyses were limited to haloperidol, risperidone, olanzapine, quetiapine, and aripiprazole.

neurodevelopmentpregnancy exposure with childhood follow-upUnplanned exposure

Public-source certainty descriptor: Moderate for attenuation of the class association; low for individual drugs and not transferable to unstudied molecules or formulations.
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate for attenuation of the class association; low for individual drugs and not transferable to unstudied molecules or formulations.
Comparator: unexposed children
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Any NDD: unadjusted HR 1.91 (95% CI 1.79–2.03) and adjusted HR 1.08 (1.01–1.17); aripiprazole adjusted HR 1.36 (1.14–1.63) was a possible signal requiring replication, not causal proof.

Limitations

Claims exposure, residual confounding, incomplete adherence, live-birth/follow-up selection, and limited individual-drug power; the data window predates multiple inventory agents and did not establish route- or LAI-specific effects.

Public-source disposition — not a commissioned recommendation

Do not present a class neurodevelopmental signal as established; still provide routine developmental surveillance.

Open sources, mapped records, and appraisal controls

Mapped medication records

HaloperidolMED-075
RisperidoneMED-098
OlanzapineMED-100
QuetiapineMED-101
AripiprazoleMED-103

Linked sources

neurodevelopmentEXT-077 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-117
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-040Module B

Provisional public source

Quetiapine and aripiprazole serum concentrations can fall substantially during pregnancy.

pharmacokineticspregnancyUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: moderate—observational TDM cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—observational TDM cohort
Comparator: nonpregnant baseline/postpartum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

More than 50% lower concentrations in many pregnancies in a therapeutic-drug-monitoring cohort

Limitations

Selected TDM population, variable sampling, and no universal therapeutic target.

Public-source disposition — not a commissioned recommendation

Assess emerging symptoms as possible underexposure and reassess any dose escalation soon after delivery.

Open sources, mapped records, and appraisal controls

Mapped medication records

QuetiapineMED-101
Quetiapine extended-releaseMED-053
AripiprazoleMED-103
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130

Linked sources

pharmacokineticsEXT-078 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-118
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-041Module B

Evidence gap

Clozapine reproductive evidence is too sparse for a reliable malformation estimate, while maternal metabolic and hematologic risks require active management.

evidence gap/clinical riskpregnancyStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low for fetal estimates; established maternal adverse-effect profile
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for fetal estimates; established maternal adverse-effect profile
Comparator: other antipsychotics or no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Case reports/series and small cohorts; no precise comparative RR

Limitations

Extreme confounding by treatment resistance and publication bias.

Public-source disposition — not a commissioned recommendation

Often continue a uniquely effective regimen with multidisciplinary metabolic, ANC, concentration, bowel, and neonatal planning.

Open sources, mapped records, and appraisal controls

Mapped medication records

ClozapineMED-097

Linked sources

evidence gap/clinical riskEXT-079 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-119
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-042Module B

Provisional public source

Clozapine is generally avoided during breastfeeding because infant data include sedation and possible agranulocytosis.

lactationlactationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low—few case reports but high-severity potential
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—few case reports but high-severity potential
Comparator: no breast-milk exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Among four reported breastfed infants summarized by LactMed, one had drowsiness and one possible agranulocytosis

Limitations

Tiny denominator, uncertain causality, and reporting bias.

Public-source disposition — not a commissioned recommendation

Prefer an alternative; if exceptional breastfeeding is chosen, use intensive infant CBC and clinical monitoring.

Open sources, mapped records, and appraisal controls

Mapped medication records

ClozapineMED-097

Linked sources

lactationEXT-080 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-120
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-043Module B

Evidence gap

Published LAI antipsychotic pregnancy evidence is limited to small case reports and case series and cannot establish equivalence to oral therapy.

evidence gappregnancyStable continuationUnplanned exposure

Public-source certainty descriptor: very low—case literature
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—case literature
Comparator: oral antipsychotic or no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

2024 review: 19 publications, 74 women, 77 pregnancies; 47 SGA-LAI and 30 FGA-LAI exposures

Limitations

Publication bias, heterogeneous products/doses, no valid comparator, limited long-term follow-up.

Public-source disposition — not a commissioned recommendation

Base decisions on adherence/relapse benefit, parent-molecule evidence, and product-specific exposure tail—not assumed LAI safety.

Open sources, mapped records, and appraisal controls

Mapped medication records

Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Pipotiazine palmitateMED-134

Linked sources

evidence gapEXT-081 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-121
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-044Module B

Provisional public source

Zuclopenthixol acetate is a short-acting injection and must not be conflated with long-acting zuclopenthixol decanoate.

formulation distinctionacute injectionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: product/formulation fact
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: product/formulation fact
Comparator: zuclopenthixol decanoate
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Different ester and exposure duration

Limitations

Brand and availability vary by country.

Public-source disposition — not a commissioned recommendation

Record ester, date, dose, and expected duration before pregnancy or lactation counseling.

Open sources, mapped records, and appraisal controls

Mapped medication records

Zuclopenthixol acetateMED-133

Linked sources

formulation distinctionEXT-082 · Not formally appraised
MHRA ProductsR-MHRA-PI · Dynamic · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-122
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-045Module B

Provisional public source

Olanzapine pamoate requires prolonged post-injection observation because of post-injection delirium/sedation syndrome.

formulation safety requirementafter every pamoate injectionSwitch before conception

Public-source certainty descriptor: regulatory label
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory label
Comparator: oral or short-acting IM olanzapine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Current US label requires 3-hour observation in a registered facility

Limitations

US product requirements; does not quantify pregnancy-specific syndrome risk.

Public-source disposition — not a commissioned recommendation

Do not substitute pamoate for oral/short-acting IM and maintain the mandated observation process during pregnancy.

Open sources, mapped records, and appraisal controls

Mapped medication records

Olanzapine pamoateMED-126

Linked sources

formulation safety requirementEXT-083 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-123
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-046Module B

Provisional public source

Olanzapine has comparatively substantial lactation experience with generally low infant serum exposure.

lactationlactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate—case series and PK reports
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—case series and PK reports
Comparator: other antipsychotics with less milk data
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Infant serum often undetectable; occasional sedation or abnormal movements reported

Limitations

Healthy-term selection and limited high-dose/LAI infant data.

Public-source disposition — not a commissioned recommendation

Often a monitored breastfeeding option; watch feeding, sedation, weight, tremor, and EPS.

Open sources, mapped records, and appraisal controls

Mapped medication records

OlanzapineMED-100
Olanzapine pamoateMED-126
Olanzapine short-acting intramuscularMED-136

Linked sources

lactationEXT-084 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-124
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-047Module B

Provisional public source

Quetiapine generally produces very low milk transfer at commonly used doses.

lactationlactationNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low-to-moderate—PK reports and case series
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low-to-moderate—PK reports and case series
Comparator: other antipsychotics
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Usually low relative infant exposure; no single threshold guarantees safety

Limitations

Limited high-dose, preterm, and poly-sedative data.

Public-source disposition — not a commissioned recommendation

Frequently preferred when efficacy is suitable; monitor drowsiness, feeding, weight, and development.

Open sources, mapped records, and appraisal controls

Mapped medication records

QuetiapineMED-101
Quetiapine extended-releaseMED-053

Linked sources

lactationEXT-085 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-125
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-048Module B

Provisional public source

Aripiprazole can suppress prolactin and impair milk production despite low milk concentrations.

lactationlactogenesis and ongoing lactationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: low—case reports/series with plausible pharmacology
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—case reports/series with plausible pharmacology
Comparator: non-prolactin-lowering antipsychotic
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Case series/reports of lactation failure or reduced supply; no reliable incidence

Limitations

Confounded by prematurity, delivery factors, illness, and feeding support.

Public-source disposition — not a commissioned recommendation

Counsel before delivery and monitor milk supply plus infant hydration/weight; switch only if clinically safe.

Open sources, mapped records, and appraisal controls

Mapped medication records

AripiprazoleMED-103
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130

Linked sources

lactationEXT-086 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-126
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-049Module B

Provisional public source

Risperidone lactation exposure is usually modest but infant adverse-effect reports and limited LAI data warrant closer monitoring.

lactationlactationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: low—case series and reports
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—case series and reports
Comparator: olanzapine/quetiapine or no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Low-to-moderate milk exposure; reported sedation, feeding, respiratory, and movement symptoms

Limitations

Small denominator and almost no formulation-specific LAI infant data.

Public-source disposition — not a commissioned recommendation

Monitor infant alertness, feeding, weight, breathing, and EPS; prefer data-rich alternatives for a newborn if equally effective.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactationEXT-087 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-127
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-050Module B

Evidence gap

Paliperidone lacks a robust published lactation series, and long-acting formulations cannot be timed around feeds.

lactation evidence gaplactation after oral or LAI exposureSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low
Comparator: data-rich antipsychotics
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable infant-outcome rate

Limitations

Inference from risperidone metabolism does not establish paliperidone or LAI safety.

Public-source disposition — not a commissioned recommendation

Prefer a direct-evidence alternative when clinically equivalent or use enhanced infant monitoring.

Open sources, mapped records, and appraisal controls

Mapped medication records

PaliperidoneMED-099
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125

Linked sources

lactation evidence gapEXT-088 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-0F9C04117121 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-128
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-051Module B

Evidence gap

Lurasidone pregnancy and lactation evidence remains limited despite no established malformation signal.

evidence gappregnancy and postpartumStable continuationNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: very low for PK magnitude; low for reproductive safety
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for PK magnitude; low for reproductive safety
Comparator: same patient postpartum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Single bipolar PK case: 0–4.7 ng/mL in pregnancy versus 10–12 ng/mL postpartum

Limitations

One PK case cannot define dosing; small pregnancy/lactation denominators.

Public-source disposition — not a commissioned recommendation

Continue a successful regimen with symptom monitoring; prefer data-rich alternatives for new starts when equally suitable.

Open sources, mapped records, and appraisal controls

Mapped medication records

LurasidoneMED-106

Linked sources

evidence gapEXT-089 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: 34291994
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-129
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-052Module B

Evidence gap

Asenapine, iloperidone, brexpiprazole, cariprazine, lumateperone, and pimavanserin lack adequate human pregnancy cohorts for drug-specific risk estimates.

evidence gapany pregnancy exposureNew initiationUnplanned exposure

Public-source certainty descriptor: very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low
Comparator: not estimable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable molecule-specific rate

Limitations

Sparse exposures, product heterogeneity, and lack of long-term infant follow-up.

Public-source disposition — not a commissioned recommendation

Prefer a data-rich effective agent for initiation; do not abruptly stop a uniquely effective newer agent.

Open sources, mapped records, and appraisal controls

Mapped medication records

AsenapineMED-104
IloperidoneMED-105
BrexpiprazoleMED-107
CariprazineMED-108
LumateperoneMED-109
PimavanserinMED-110

Linked sources

drug-specific signal; evidence gap; route/formulation principleEXT-074 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-130
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-053Module B

Evidence gap

Lactation data for newer dopamine-active agents are sparse and product properties matter.

lactation evidence gaplactationDelivery/postpartum/lactation

Public-source certainty descriptor: very low-to-low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low-to-low
Comparator: data-rich antipsychotics
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Brexpiprazole may reduce supply; cariprazine has long-lived metabolites; lumateperone milk amounts appear low but infant outcomes are absent

Limitations

Case reports or small milk PK studies cannot establish infant safety.

Public-source disposition — not a commissioned recommendation

Usually prefer a better-studied agent for a newborn/preterm infant, especially with cariprazine.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactation evidence gapEXT-090 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-131
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-054Module B

Evidence gap

Human pregnancy data are insufficient for xanomeline/trospium, and dopamine-antipsychotic neonatal EPS warnings should not be mechanically extrapolated.

label evidence gappregnancyStable continuationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: regulatory label; very low clinical evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory label; very low clinical evidence
Comparator: not estimable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate human pregnancy cohort

Limitations

New product, different mechanism, no comparative pregnancy PK or child follow-up.

Public-source disposition — not a commissioned recommendation

Prefer data-rich options for initiation and use product-specific maternal/newborn monitoring if continued.

Open sources, mapped records, and appraisal controls

Mapped medication records

Xanomeline/trospium chlorideMED-111

Linked sources

label evidence gapEXT-091 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-132
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-055Module B

Evidence gap

Milsaperidone was FDA approved in February 2026 and had no adequate human pregnancy outcome cohort by the evidence cutoff.

2026 status/evidence gapstatus as of 2026-07-29New initiation

Public-source certainty descriptor: regulatory status high; pregnancy evidence very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory status high; pregnancy evidence very low
Comparator: not applicable
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

FDA approval 2026-02-20; DailyMed marketing start 2026-07-01

Limitations

Marketing-start field does not establish broad commercial availability; postmarketing pregnancy denominator is negligible.

Public-source disposition — not a commissioned recommendation

Do not initiate as a pregnancy first choice when a data-rich equivalent exists; state risk is unknown, not low.

Open sources, mapped records, and appraisal controls

Mapped medication records

MilsaperidoneMED-112

Linked sources

2026 status/evidence gapEXT-092 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-83D7C0A553FE · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-133
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-056Module B

Evidence gap

Fixed antipsychotic combinations require component-by-component and product-specific assessment; olanzapine evidence alone is insufficient.

combination assessmentpregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low—combination-specific evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low—combination-specific evidence
Comparator: separately titrated components
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No combination-specific comparative pregnancy estimate

Limitations

Component cohorts cannot detect interaction effects or fixed-ratio consequences.

Public-source disposition — not a commissioned recommendation

Prefer separable components when clinically equivalent and review every component exposure.

Open sources, mapped records, and appraisal controls

Mapped medication records

Olanzapine/fluoxetineMED-113
Olanzapine/samidorphanMED-114

Linked sources

combination assessment; label safety warningEXT-093 · Not formally appraised
combination assessmentEXT-094 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-134
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-057Module B

Provisional public source

Samidorphan can precipitate severe opioid withdrawal in opioid-dependent patients and complicate opioid analgesia around delivery.

label safety warninginitiation, emergency analgesia, labor/deliveryNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: regulatory label
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: regulatory label
Comparator: olanzapine without samidorphan
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Severe withdrawal risk and opioid blockade; product-specific opioid-free intervals apply

Limitations

No pregnancy-specific comparative trial; opioid history may be incompletely disclosed.

Public-source disposition — not a commissioned recommendation

Verify all opioid exposure and create an anesthesia/analgesia plan before delivery.

Open sources, mapped records, and appraisal controls

Mapped medication records

Olanzapine/samidorphanMED-114

Linked sources

combination assessment; label safety warningEXT-093 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-135
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-058Module B

Provisional public source

Olanzapine/fluoxetine requires assessment of both olanzapine metabolic/neonatal risks and fluoxetine SSRI-specific neonatal/bleeding considerations.

combination assessmentpregnancy and near deliveryDelivery/postpartum/lactation

Public-source certainty descriptor: low—component-based inference
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: low—component-based inference
Comparator: olanzapine or fluoxetine alone
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No combination-specific effect estimate

Limitations

Cannot separate component or interaction effects in sparse combination data.

Public-source disposition — not a commissioned recommendation

Review indication, fixed ratio, serotonergic co-medications, metabolic risk, and neonatal plan.

Open sources, mapped records, and appraisal controls

Mapped medication records

Olanzapine/fluoxetineMED-113

Linked sources

combination assessmentEXT-094 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-136
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-059Module B

Provisional public source

ACOG identifies haloperidol or olanzapine with lorazepam as acute pharmacotherapy options for postpartum psychosis while awaiting lithium response.

emergency guideline recommendationacute postpartum psychosisDelivery/postpartum/lactation

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: no acute treatment/other emergency regimen
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No comparative pregnancy effect estimate

Limitations

Postpartum emergency guidance is not a fetal-malformation study; regimen must fit medical status, sedation, QT, and feeding plans.

Public-source disposition — not a commissioned recommendation

Treat postpartum psychosis as an emergency and coordinate psychiatry, obstetrics, and neonatal/feeding care.

Open sources, mapped records, and appraisal controls

Mapped medication records

HaloperidolMED-075
OlanzapineMED-100
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-137
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-060Module B

Provisional public source

When haloperidol is used for postpartum psychosis/agitation, ACOG advises prophylaxis/management of dystonia with an anticholinergic such as diphenhydramine.

emergency adverse-effect managementacute postpartum treatmentDelivery/postpartum/lactation

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: haloperidol without EPS prophylaxis
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No effect estimate

Limitations

Diphenhydramine has its own maternal sedation and lactation considerations and is outside this antipsychotic profile.

Public-source disposition — not a commissioned recommendation

Include EPS prevention/response in the emergency order set and monitor maternal/newborn sedation.

Open sources, mapped records, and appraisal controls

Mapped medication records

HaloperidolMED-075
Haloperidol short-acting injectionMED-135

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-138
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-061Module B

Evidence gap

Rare, legacy, international, inhaled, and acute parenteral antipsychotics lack robust molecule- and formulation-specific pregnancy cohorts.

evidence gappregnancyStable continuationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low
Comparator: data-rich antipsychotics
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No stable drug-specific rate

Limitations

Mixed indications, country-specific products, route heterogeneity, and tiny denominators.

Public-source disposition — not a commissioned recommendation

Prefer data-rich agents for initiation; preserve a uniquely effective regimen with explicit formulation and neonatal planning.

Open sources, mapped records, and appraisal controls

Mapped medication records

Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Droperidol injectionMED-138

Linked sources

drug-specific signal; evidence gap; route/formulation principleEXT-074 · Not formally appraised
neonatal safetyEXT-076 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-139
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-062Module B

Provisional public source

A short-acting emergency route changes onset and maternal monitoring but does not create separate reassuring reproductive evidence.

route/formulation principleacute pregnancy or postpartum emergency exposureStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: very low for fetal comparison; high for route distinction
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: very low for fetal comparison; high for route distinction
Comparator: oral maintenance exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No comparative fetal-safety estimate by IM/IV route

Limitations

Emergency cohorts are confounded by severe agitation, restraint, co-sedatives, and medical instability.

Public-source disposition — not a commissioned recommendation

Stabilize the patient, use route-specific cardiorespiratory/QT monitoring, and document cumulative late exposure for the newborn team.

Open sources, mapped records, and appraisal controls

Mapped medication records

Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138

Linked sources

drug-specific signal; evidence gap; route/formulation principleEXT-074 · Not formally appraised
guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-140
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-063Module B

Provisional public source

A stable patient should not be switched reflexively after conception solely to use a medicine with more pregnancy data.

guideline decision principleafter conceptionStable continuationSwitch before conception

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: continuing an effective regimen
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single effect estimate; relapse and fetal polypharmacy tradeoff

Limitations

Important exceptions include valproate and compelling toxicity/ineffectiveness; individual history controls the decision.

Public-source disposition — not a commissioned recommendation

Continue most effective regimens while correcting dose/monitoring; make switches only for a clear net clinical benefit.

Open sources, mapped records, and appraisal controls

Mapped medication records

Lithium carbonateMED-056
Lithium citrateMED-057
Valproic acidMED-058
Divalproex sodiumMED-059
Valproate sodiumMED-060
CarbamazepineMED-061
LamotrigineMED-062
OxcarbazepineMED-063
ChlorpromazineMED-073
FluphenazineMED-074
HaloperidolMED-075
PerphenazineMED-076
TrifluoperazineMED-077
ThiothixeneMED-078
Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
ClozapineMED-097
RisperidoneMED-098
PaliperidoneMED-099
OlanzapineMED-100
QuetiapineMED-101
ZiprasidoneMED-102
AripiprazoleMED-103
AsenapineMED-104
IloperidoneMED-105
LurasidoneMED-106
BrexpiprazoleMED-107
CariprazineMED-108
LumateperoneMED-109
PimavanserinMED-110
Xanomeline/trospium chlorideMED-111
MilsaperidoneMED-112
Olanzapine/fluoxetineMED-113
Olanzapine/samidorphanMED-114
Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138
Quetiapine extended-releaseMED-053

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-141
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-064Module B

Provisional public source

If an antipsychotic was effective throughout pregnancy, routine postpartum switching solely for lactation is usually discouraged.

lactation decision principlepostpartum/lactationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: guideline recommendation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: guideline recommendation
Comparator: switching to a different agent
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single effect estimate

Limitations

Clozapine, milk-supply goals with aripiprazole, infant prematurity/illness, and long-lived/LAI exposure may change the decision.

Public-source disposition — not a commissioned recommendation

Preserve maternal stability while conducting a separate drug- and infant-specific lactation assessment.

Open sources, mapped records, and appraisal controls

Mapped medication records

ChlorpromazineMED-073
FluphenazineMED-074
HaloperidolMED-075
PerphenazineMED-076
TrifluoperazineMED-077
ThiothixeneMED-078
Loxapine (oral)MED-079
Loxapine inhalation powderMED-080
MolindoneMED-081
PimozideMED-082
ThioridazineMED-083
ProchlorperazineMED-084
LevomepromazineMED-085
Flupentixol (oral)MED-086
Zuclopenthixol (oral/short-acting)MED-087
Amisulpride (oral psychiatric)MED-088
SulpirideMED-089
TiaprideMED-090
ZotepineMED-091
SertindoleMED-092
BlonanserinMED-093
MelperoneMED-094
PenfluridolMED-095
Pipotiazine (oral)MED-096
ClozapineMED-097
RisperidoneMED-098
PaliperidoneMED-099
OlanzapineMED-100
QuetiapineMED-101
ZiprasidoneMED-102
AripiprazoleMED-103
AsenapineMED-104
IloperidoneMED-105
LurasidoneMED-106
BrexpiprazoleMED-107
CariprazineMED-108
LumateperoneMED-109
PimavanserinMED-110
Xanomeline/trospium chlorideMED-111
MilsaperidoneMED-112
Olanzapine/fluoxetineMED-113
Olanzapine/samidorphanMED-114
Haloperidol decanoateMED-115
Fluphenazine decanoateMED-116
Risperidone microspheres (Risperdal Consta)MED-117
Risperidone extended-release injectable suspension (Rykindo)MED-118
Risperidone extended-release subcutaneous suspension (monthly)MED-119
Risperidone extended-release subcutaneous suspension (monthly or every 2 months)MED-120
Risperidone extended-release intramuscular suspension (monthly)MED-121
Paliperidone palmitate 1-month (Invega Sustenna)MED-122
Paliperidone palmitate 1-month (Erzofri)MED-123
Paliperidone palmitate 3-monthMED-124
Paliperidone palmitate 6-monthMED-125
Olanzapine pamoateMED-126
Aripiprazole monohydrate 1-monthMED-127
Aripiprazole monohydrate 2-monthMED-128
Aripiprazole lauroxilMED-129
Aripiprazole lauroxil initiation formulationMED-130
Flupentixol decanoateMED-131
Zuclopenthixol decanoateMED-132
Zuclopenthixol acetateMED-133
Pipotiazine palmitateMED-134
Haloperidol short-acting injectionMED-135
Olanzapine short-acting intramuscularMED-136
Ziprasidone intramuscularMED-137
Droperidol injectionMED-138
Quetiapine extended-releaseMED-053

Linked sources

guideline recommendation; emergency guideline recommendation; emergency adverse-effect management; guideline decision principle; lactation decision principleEXT-072 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-142
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

B-065Module B

Provisional public source

Breastfed infants in the MONEAD cohort generally had substantially lower antiseizure-medicine concentrations than their mothers.

lactation pharmacokineticsearly lactationDelivery/postpartum/lactation

Public-source certainty descriptor: moderate—prospective mother-infant cohort for studied agents
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: moderate—prospective mother-infant cohort for studied agents
Comparator: maternal serum
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Infant concentrations substantially lower than maternal concentrations across studied ASMs

Limitations

Does not cover every ASM equally, rare adverse effects, premature/ill infants, or long-term outcomes.

Public-source disposition — not a commissioned recommendation

Support breastfeeding for many ASM regimens with agent-specific monitoring rather than treating the class as uniformly safe or unsafe.

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactation pharmacokineticsEXT-095 · Not formally appraised
neurodevelopment; risk estimate; evidence gap; guideline recommendationEXT-062 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-143
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-001Module C

Provisional public source

Methadone and buprenorphine are recommended treatments for opioid use disorder in pregnancy; medically supervised withdrawal is not preferred because relapse and treatment loss can be dangerous.

guideline_positionPregnancyStable continuationNew initiation

Public-source certainty descriptor: High guideline consensus; not GRADE-rated here
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High guideline consensus; not GRADE-rated here
Comparator: Agonist treatment versus withdrawal or untreated OUD
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single pooled effect used

Limitations

Guideline recommendation integrates indirect and observational evidence; access and prior response matter

Public-source disposition — not a commissioned recommendation

Continue stable treatment; offer methadone or buprenorphine for new OUD; do not force withdrawal

Open sources, mapped records, and appraisal controls

Mapped medication records

Methadone (oral OUD treatment)MED-212
Buprenorphine sublingualMED-213
Buprenorphine/naloxone transmucosalMED-215

Linked sources

guideline_position; comparative_effectivenessEXT-096 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-B3BA32CB0CF7 · Unverified metadata

Citation controls

PMID: 21142534
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-144
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-002Module C

Provisional public source

Buprenorphine produced less severe neonatal withdrawal-treatment burden than methadone among infants in the MOTHER randomized trial, while both drugs treated maternal OUD.

comparative_effectivenessPregnancy through neonatal hospitalizationStable continuationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate; randomized trial with important attrition
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate; randomized trial with important attrition
Comparator: Sublingual buprenorphine versus methadone
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Primary trial reported less morphine treatment and shorter hospital course with buprenorphine

Limitations

Selected trial population and differential discontinuation limit generalizability; neonatal protocols have evolved

Public-source disposition — not a commissioned recommendation

Do not switch a stable patient solely for neonatal outcome; use in shared initial-treatment choice

Open sources, mapped records, and appraisal controls

Mapped medication records

Methadone (oral OUD treatment)MED-212
Buprenorphine sublingualMED-213
Buprenorphine/naloxone transmucosalMED-215

Linked sources

guideline_position; comparative_effectivenessEXT-096 · Not formally appraised
Opioid Use Disorder in Pregnancy clinical recommendationG-ASAM-ACOG-OUD · 2017 basis · Still officially hosted

Citation controls

PMID: 21142534
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-145
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-003Module C

Provisional public source

A 2024 nationwide Medicaid cohort did not find worse major congenital malformation, preterm birth, low birth weight, respiratory or cesarean outcomes with first-trimester buprenorphine/naloxone versus buprenorphine alone and observed lower risk for some neonatal outcomes including NOWS.

comparative_safetyFirst trimester and pregnancyStable continuationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate-low; large observational comparative cohort
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate-low; large observational comparative cohort
Comparator: Buprenorphine/naloxone versus buprenorphine alone or switch to monoproduct
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No excess in prespecified major outcomes; lower observed NOWS risk

Limitations

Residual confounding and exposure misclassification remain; does not prove combination superiority

Public-source disposition — not a commissioned recommendation

Do not automatically switch a stable combination-product patient to monoproduct

Open sources, mapped records, and appraisal controls

Mapped medication records

Buprenorphine sublingualMED-213
Buprenorphine/naloxone transmucosalMED-215

Linked sources

comparative_safetyEXT-097 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-B3BA32CB0CF7 · Unverified metadata

Citation controls

PMID: 39133511
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-146
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-004Module C

Provisional public source

Belbuca is a buccal buprenorphine pain formulation, not an interchangeable OUD formulation; pregnancy counseling must address the pain indication, opioid dependence, neonatal opioid withdrawal, and product-specific conversion.

formulation_boundaryAny pregnancy exposureUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: High identity certainty; low direct pregnancy evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High identity certainty; low direct pregnancy evidence
Comparator: Belbuca versus transmucosal OUD products
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No direct comparative pregnancy effectiveness estimate

Limitations

Label evidence is not an OUD trial and formulations are not dose-interchangeable

Public-source disposition — not a commissioned recommendation

Verify indication and formulation; never improvise conversion or abrupt cessation

Open sources, mapped records, and appraisal controls

Mapped medication records

Buprenorphine buccal film (pain formulation)MED-214

Linked sources

formulation_boundaryEXT-098 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-147
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-005Module C

Provisional public source

In a 2026 open-label randomized trial, weekly extended-release buprenorphine/CAM2038 produced more illicit-opioid-negative weekly urine samples during pregnancy than sublingual buprenorphine.

comparative_effectiveness6 to 30 weeks gestation through deliveryDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate; randomized but open-label and modest-sized
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate; randomized but open-label and modest-sized
Comparator: Weekly Brixadi/CAM2038 versus sublingual buprenorphine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

82.5% versus 72.6%; mean difference 9.84 percentage points, 95% CI 1.72 to 17.95

Limitations

140 participants at 13 US sites; almost all were already taking sublingual buprenorphine; limited diversity and site variation; the current corrected article was used

Public-source disposition — not a commissioned recommendation

Weekly Brixadi is now a supported option when product-specific induction, access, and preference align

Open sources, mapped records, and appraisal controls

Mapped medication records

Buprenorphine extended-release weekly/monthly injectionMED-217

Linked sources

comparative_effectivenessEXT-099 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-AD7BFFC5936D · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-148
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-006Module C

Provisional public source

The 2026 weekly CAM2038 result must not be extrapolated to monthly Brixadi, Sublocade, Buvidal labeling, Probuphine, or Sixmo; these formulations differ in delivery, residual release, removability, jurisdiction, and evidence.

formulation_boundaryPregnancy and postpartumStable continuationNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: High boundary certainty; very low direct evidence for several formulations
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High boundary certainty; very low direct evidence for several formulations
Comparator: Other depot or implant formulations versus weekly CAM2038
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Direct randomized pregnancy evidence applies to weekly CAM2038 only

Limitations

Absence of direct evidence does not prove harm; forced switching can destabilize OUD

Public-source disposition — not a commissioned recommendation

Continue stable depot only after individualized review; prefer directly studied or established formulation for new initiation when feasible

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

formulation_boundary; neonatal_outcomeEXT-100 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-A7521D27C108 · Unverified metadata

Citation controls

PMID: 41837971
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-149
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-007Module C

Provisional public source

In the 2026 trial, estimates for infant opioid treatment for NOWS and treatment duration were imprecise and compatible with benefit or harm; the trial did not establish neonatal equivalence.

neonatal_outcomeLate pregnancy and neonatal periodDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate-low; secondary outcomes and variable site scoring
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate-low; secondary outcomes and variable site scoring
Comparator: Weekly CAM2038 versus sublingual buprenorphine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Infant opioid treatment: 30.2% versus 26.5%, RR 1.14 (98% CI 0.54–1.99), P=.64; mean treatment days: 10.9 (SE 2.2) versus 14.8 (SE 3.0), ratio 0.73 (98% CI 0.36–1.51), P=.28.

Limitations

Trial not powered to prove neonatal equivalence; NOWS assessment varied by site

Public-source disposition — not a commissioned recommendation

Plan standard newborn observation; do not promise prevention of NOWS

Open sources, mapped records, and appraisal controls

Mapped medication records

Buprenorphine extended-release weekly/monthly injectionMED-217

Linked sources

formulation_boundary; neonatal_outcomeEXT-100 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-AD7BFFC5936D · Unverified metadata

Citation controls

PMID: 41837971
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-150
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-008Module C

Provisional public source

Naltrexone continuation in a patient already stable and opioid-free is a different decision from initiating naltrexone during pregnancy, which requires abstinence and can precipitate withdrawal.

exposure_managementPreconception, pregnancy, and postpartumStable continuationNew initiationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Low; observational cohorts and case series
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low; observational cohorts and case series
Comparator: Continuation versus new induction; oral versus extended-release
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Small cohorts and case series are reassuring but imprecise

Limitations

Much smaller evidence base than methadone/buprenorphine; selection of stable patients; analgesia and overdose risk after discontinuation matter

Public-source disposition — not a commissioned recommendation

Use shared decision-making for continuation; generally do not initiate for OUD without specialist review

Open sources, mapped records, and appraisal controls

Mapped medication records

Naltrexone oralMED-221
Naltrexone extended-release injectionMED-222

Linked sources

exposure_managementEXT-101 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-0F537DC7655A · Unverified metadata

Citation controls

PMID: 38227945
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-151
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-009Module C

Provisional public source

Naloxone should not be withheld in a suspected opioid overdose because of pregnancy; naloxone and nalmefene rescue products reverse overdose but do not treat OUD.

emergency_guidanceAcute overdose in pregnancy or postpartumDelivery/postpartum/lactation

Public-source certainty descriptor: High emergency consensus; pregnancy comparative trials infeasible
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High emergency consensus; pregnancy comparative trials infeasible
Comparator: Rescue treatment versus no reversal
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Immediate reversal benefit outweighs fetal concern in life-threatening maternal hypoxia

Limitations

Recurrent toxicity and precipitated withdrawal require observation; nalmefene has longer action and less pregnancy experience

Public-source disposition — not a commissioned recommendation

Support ventilation, give rescue antagonist, activate emergency care, repeat/observe per product and protocol

Open sources, mapped records, and appraisal controls

Mapped medication records

Naloxone rescue productsMED-223
Nalmefene nasal sprayMED-229

Linked sources

emergency_guidanceEXT-102 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-B3BA32CB0CF7 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-152
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-010Module C

Provisional public source

Breastfeeding is generally supported for patients stable on methadone or buprenorphine when there is no separate contraindication; current nonprescribed exposure is assessed separately.

lactation_positionPostpartum lactationStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate guideline consensus; observational infant evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate guideline consensus; observational infant evidence
Comparator: Breastfeeding versus formula in stable treated OUD
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Low milk transfer for buprenorphine; established experience for both

Limitations

Maternal stability, HIV policy, polysubstance exposure, infant prematurity and sedation require individual review

Public-source disposition — not a commissioned recommendation

Encourage breastfeeding when clinically appropriate; monitor infant and coordinate pediatric care

Open sources, mapped records, and appraisal controls

Mapped medication records

Methadone (oral OUD treatment)MED-212
Buprenorphine sublingualMED-213
Buprenorphine/naloxone transmucosalMED-215

Linked sources

lactation_positionEXT-103 · Not formally appraised
lactation_positionEXT-143 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-153
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-011Module C

Provisional public source

Lofexidine is an alpha-2 agonist for opioid-withdrawal symptoms, not maintenance treatment; pregnancy evidence is very sparse and withdrawal management should not replace methadone or buprenorphine treatment for OUD.

indication_boundaryPregnancyStable continuationNew initiationSwitch before conception

Public-source certainty descriptor: Very low direct pregnancy evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low direct pregnancy evidence
Comparator: Symptom management versus evidence-based MOUD
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate pregnancy comparative outcome data

Limitations

Maternal hypotension and bradycardia are clinically relevant; label animal findings do not quantify human risk

Public-source disposition — not a commissioned recommendation

Do not initiate as a substitute for MOUD; specialist-only if considered

Open sources, mapped records, and appraisal controls

Mapped medication records

LofexidineMED-224

Linked sources

indication_boundaryEXT-104 · Not formally appraised
Opioid Use Disorder in Pregnancy clinical recommendationG-ASAM-ACOG-OUD · 2017 basis · Still officially hosted

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-154
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-012Module C

Provisional public source

Slow-release oral morphine is a jurisdiction-specific alternative OUD treatment with substantially less pregnancy evidence than methadone or buprenorphine and is not FDA-approved for OUD.

regulatory_boundaryPregnancy and lactationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Low direct evidence; high regulatory-status certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low direct evidence; high regulatory-status certainty
Comparator: SROM versus methadone/buprenorphine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No robust pregnancy comparative estimate

Limitations

Product availability and protocols vary by country; neonatal opioid withdrawal can occur

Public-source disposition — not a commissioned recommendation

Use only under the governing specialist protocol; do not improvise a US substitution

Open sources, mapped records, and appraisal controls

Mapped medication records

Morphine sulfate prolonged-release (OUD use)MED-225

Linked sources

regulatory_boundary; emergency_guidanceEXT-105 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-155
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-013Module C

Provisional public source

No AUD pharmacotherapy has a large pregnancy-specific efficacy-and-safety evidence base comparable to OUD agonist treatment; continued heavy alcohol exposure itself is a major maternal-fetal hazard.

evidence_synthesisPreconception through postpartumStable continuationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate guideline consensus; low drug-specific pregnancy evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate guideline consensus; low drug-specific pregnancy evidence
Comparator: Medication plus care versus continued AUD or psychosocial care alone
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pooled pregnancy efficacy estimate

Limitations

Medication cohorts are small and confounded; the risk of untreated severe AUD varies greatly

Public-source disposition — not a commissioned recommendation

Prioritize abstinence-oriented psychosocial and medical care; consider medicine only through individualized comparison

Open sources, mapped records, and appraisal controls

Mapped medication records

AcamprosateMED-226
DisulfiramMED-227
Nalmefene oralMED-228
BaclofenMED-230
OndansetronMED-231
VareniclineMED-232

Linked sources

evidence_synthesis; indication_and_withdrawal; indication_boundaryEXT-106 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-1AF097C9A8EB · Unverified metadata

Citation controls

PMID: 33830479
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-156
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-014Module C

Provisional public source

A small acamprosate pregnancy cohort did not identify a clear adverse outcome pattern, but it cannot establish safety or pregnancy effectiveness.

pregnancy_safetyPregnancyStable continuation

Public-source certainty descriptor: Low; small observational study
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low; small observational study
Comparator: Acamprosate-exposed versus unexposed pregnancies
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Small cohort; no precise causal estimate used

Limitations

Confounding by alcohol use and limited power for uncommon outcomes

Public-source disposition — not a commissioned recommendation

May consider when relapse risk is high and behavioral care alone is insufficient; review renal function and adherence

Open sources, mapped records, and appraisal controls

Mapped medication records

AcamprosateMED-226

Linked sources

pregnancy_safetyEXT-107 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-A59B9BE10586 · Unverified metadata

Citation controls

PMID: 30152012
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-157
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-015Module C

Provisional public source

Disulfiram is generally avoided in pregnancy because its aversive reaction can cause severe maternal hemodynamic stress and developmental evidence is limited; it should not be used when drinking is likely.

guideline_positionPregnancyStable continuationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: Low direct evidence; moderate consensus to avoid
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low direct evidence; moderate consensus to avoid
Comparator: Disulfiram versus psychosocial or other relapse-prevention care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable pregnancy effectiveness or safety estimate

Limitations

Historical reports are sparse; avoidance reflects mechanism and uncertainty rather than a quantified malformation risk

Public-source disposition — not a commissioned recommendation

Do not newly initiate in pregnancy; reassess stable use and avoid breastfeeding absent compelling specialist rationale

Open sources, mapped records, and appraisal controls

Mapped medication records

DisulfiramMED-227

Linked sources

guideline_positionEXT-108 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-1AF097C9A8EB · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-158
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-016Module C

Provisional public source

Oral nalmefene for AUD and intranasal nalmefene for opioid overdose are different indications and formulations and must never be conflated.

formulation_boundaryAll windowsClinical-position linkage pending

Public-source certainty descriptor: High identity and regulatory certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High identity and regulatory certainty
Comparator: Selincro oral versus Opvee intranasal
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Not applicable

Limitations

Oral nalmefene is jurisdiction-specific and has inadequate pregnancy evidence

Public-source disposition — not a commissioned recommendation

Verify product and indication before every recommendation

Open sources, mapped records, and appraisal controls

Mapped medication records

Nalmefene oralMED-228
Nalmefene nasal sprayMED-229

Linked sources

formulation_boundaryEXT-109 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-159
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-017Module C

Provisional public source

Baclofen has mixed, protocol-dependent nonpregnant AUD efficacy and pregnancy experience from spasticity does not establish AUD benefit; abrupt chronic baclofen cessation can cause maternal and neonatal withdrawal problems.

indication_and_withdrawalPregnancy, delivery, and neonatal periodNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: Low; indirect and case-report evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low; indirect and case-report evidence
Comparator: Baclofen for AUD versus behavioral care or other medicines
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy AUD efficacy estimate

Limitations

Dose, renal function and indication vary; neonatal withdrawal evidence is case-based

Public-source disposition — not a commissioned recommendation

Do not initiate routinely for AUD; if chronic, avoid abrupt cessation and plan newborn observation

Open sources, mapped records, and appraisal controls

Mapped medication records

BaclofenMED-230

Linked sources

evidence_synthesis; indication_and_withdrawal; indication_boundaryEXT-106 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-11DD91A86F49 · Unverified metadata

Citation controls

PMID: 33830479
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-160
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-018Module C

Provisional public source

Ondansetron and varenicline have been studied for alcohol outcomes in selected nonpregnant populations, but neither should be initiated as routine AUD pharmacotherapy in pregnancy.

indication_boundaryPregnancyNew initiation

Public-source certainty descriptor: Low for AUD; high indication certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low for AUD; high indication certainty
Comparator: Off-label AUD use versus established AUD care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy AUD efficacy estimate

Limitations

Pregnancy safety evidence for their approved uses does not establish AUD effectiveness

Public-source disposition — not a commissioned recommendation

Verify actual indication; use separate antiemetic or smoking-cessation evidence

Open sources, mapped records, and appraisal controls

Mapped medication records

OndansetronMED-231
VareniclineMED-232

Linked sources

evidence_synthesis; indication_and_withdrawal; indication_boundaryEXT-106 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-DC7BF4DFCCC8 · Unverified metadata

Citation controls

PMID: 33830479
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-161
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-019Module C

Provisional public source

Severe alcohol withdrawal in pregnancy is a medical emergency; benzodiazepines may be required despite reproductive uncertainty because seizure, delirium and autonomic instability threaten patient and fetus.

emergency_guidanceAcute withdrawalClinical-position linkage pending

Public-source certainty descriptor: High emergency consensus; low pregnancy trial evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High emergency consensus; low pregnancy trial evidence
Comparator: Supervised medication treatment versus untreated withdrawal
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No randomized pregnancy withdrawal comparison; treatment is risk-based

Limitations

Specific regimen depends on severity, gestation and comorbidity; not a home-detox protocol

Public-source disposition — not a commissioned recommendation

Escalate to supervised care; do not advise abrupt unsupported cessation

Open sources, mapped records, and appraisal controls

Mapped medication records

AcamprosateMED-226
DisulfiramMED-227
Nalmefene oralMED-228
BaclofenMED-230
OndansetronMED-231
VareniclineMED-232

Linked sources

regulatory_boundary; emergency_guidanceEXT-105 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-C7B9F66A4C0D · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-162
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-020Module C

Evidence gap

When behavioral support alone is insufficient, nicotine-replacement therapy can be considered in pregnancy because it avoids combustion toxicants, although pregnancy cessation efficacy and optimal formulation remain uncertain.

guideline_positionPregnancyStable continuationUnplanned exposure

Public-source certainty descriptor: Moderate guideline consensus; low-to-moderate pregnancy evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate guideline consensus; low-to-moderate pregnancy evidence
Comparator: NRT plus behavioral care versus continued smoking or behavioral care alone
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single pooled effect used

Limitations

Adherence is poor in many trials; nicotine exposure continues; smoking/vaping amount and formulation differ

Public-source disposition — not a commissioned recommendation

Use shared decision-making; match patch versus intermittent product to withdrawal control and minimize concurrent smoking

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

guideline_position; comparative_safetyEXT-110 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-CF96A61CC914 · Unverified metadata

Citation controls

PMID: 40163085
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-163
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-021Module C

Provisional public source

A 2025 multinational cohort found no clear overall major-congenital-malformation increase with first-trimester varenicline, bupropion or NRT compared with smoking, but it does not establish pregnancy cessation efficacy or exclude uncommon risks.

comparative_safetyFirst trimesterUnplanned exposure

Public-source certainty descriptor: Moderate-low; large observational study
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate-low; large observational study
Comparator: Cessation medicines versus smoking in pregnancy
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No clear overall MCM elevation in studied exposure groups

Limitations

Residual confounding, adherence uncertainty and limited power for specific defects

Public-source disposition — not a commissioned recommendation

Consider bupropion or varenicline only after individualized benefit-risk review; do not label either risk-free

Open sources, mapped records, and appraisal controls

Mapped medication records

VareniclineMED-232
Bupropion sustained-release (smoking cessation)MED-238

Linked sources

guideline_position; comparative_safetyEXT-110 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-CF96A61CC914 · Unverified metadata

Citation controls

PMID: 40163085
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-164
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-022Module C

Provisional public source

An observational 2025 study suggested greater smoking-cessation effectiveness with varenicline than NRT in pregnancy, but nonadherence and unmeasured confounding limit causal interpretation.

comparative_effectivenessPregnancyDelivery/postpartum/lactation

Public-source certainty descriptor: Low-to-moderate; observational
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low-to-moderate; observational
Comparator: Varenicline versus NRT
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Direction favored varenicline; no causal estimate adopted for this manual

Limitations

Not randomized; treatment selection and adherence likely differ

Public-source disposition — not a commissioned recommendation

May be considered for a patient unlikely to quit otherwise after counseling; plan lactation separately

Open sources, mapped records, and appraisal controls

Mapped medication records

VareniclineMED-232

Linked sources

comparative_effectivenessEXT-111 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-CF96A61CC914 · Unverified metadata

Citation controls

PMID: 41424159
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-165
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-023Module C

Provisional public source

Cytisinicline/cytisine lacks adequate pregnancy and lactation evidence and was not FDA-approved at the cutoff; the 2026 complete-response action does not provide reproductive reassurance.

regulatory_and_evidence_gapPregnancy and lactationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: Very low direct evidence; regulatory status checked to cutoff
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low direct evidence; regulatory status checked to cutoff
Comparator: Cytisine versus established cessation approaches
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Pregnant/lactating participants excluded from development trials

Limitations

Complete-response details are sponsor-reported; international products/regimens vary

Public-source disposition — not a commissioned recommendation

Do not initiate in pregnancy or lactation outside authorized research

Open sources, mapped records, and appraisal controls

Mapped medication records

CytisineMED-239

Linked sources

regulatory_and_evidence_gapEXT-112 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-79C1610B6F6A · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-166
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-024Module C

Provisional public source

No medication is FDA-approved for stimulant-use disorder; contingency management is the current standard behavioral intervention, while off-label medicines require specialist selection.

guideline_positionPregnancy and nonpregnant treatmentClinical-position linkage pending

Public-source certainty descriptor: High guideline consensus; not GRADE-rated here
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High guideline consensus; not GRADE-rated here
Comparator: Behavioral standard versus off-label pharmacotherapy
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No approved pharmacologic effect estimate

Limitations

Access to contingency management varies; guideline medication evidence is mainly nonpregnant

Public-source disposition — not a commissioned recommendation

Prioritize contingency management and comprehensive care; do not reproduce research regimens casually in pregnancy

Open sources, mapped records, and appraisal controls

Mapped medication records

Bupropion plus naltrexone regimenMED-240
Prescription psychostimulant substitution approachesMED-241

Linked sources

guideline_position; exposure_boundaryEXT-113 · Not formally appraised
Clinical Practice Guideline on the Management of Stimulant Use DisorderG-ASAM-STUD · Final 2023; journal 2024 · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-167
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-025Module C

Provisional public source

In ADAPT-2, nonpregnant adults receiving bupropion plus extended-release naltrexone had a higher but modest response rate than placebo; pregnant participants were excluded.

comparative_effectivenessTwo-stage 12-week nonpregnant trialClinical-position linkage pending

Public-source certainty descriptor: Moderate for selected nonpregnant adults; no direct pregnancy evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate for selected nonpregnant adults; no direct pregnancy evidence
Comparator: Bupropion plus extended-release naltrexone versus placebo
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Weighted response 13.6% versus 2.5%

Limitations

Absolute response was modest; naltrexone requires opioid-free status; regimen is not a fixed-dose approved StUD product

Public-source disposition — not a commissioned recommendation

Do not extrapolate efficacy or fetal safety to pregnancy; specialist-only exceptional consideration

Open sources, mapped records, and appraisal controls

Mapped medication records

Bupropion plus naltrexone regimenMED-240

Linked sources

comparative_effectivenessEXT-114 · Not formally appraised
Clinical Practice Guideline on the Management of Stimulant Use DisorderG-ASAM-STUD · Final 2023; journal 2024 · Current

Citation controls

PMID: 33497547
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-168
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-026Module C

Provisional public source

Prescription psychostimulant substitution studies are regimen-specific and mainly nonpregnant; a verified therapeutic prescription is not equivalent to nonmedical methamphetamine, cocaine, or counterfeit amphetamine exposure.

exposure_boundaryPreconception through lactationNew initiationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: High conceptual certainty; low pregnancy treatment evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High conceptual certainty; low pregnancy treatment evidence
Comparator: Monitored prescription versus nonmedical stimulant
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy StUD effectiveness estimate

Limitations

Molecule, dose, ADHD indication, cardiovascular risk and diversion vary

Public-source disposition — not a commissioned recommendation

Verify indication and product; generally avoid initiating substitution in pregnancy outside specialist care or research

Open sources, mapped records, and appraisal controls

Mapped medication records

Prescription psychostimulant substitution approachesMED-241

Linked sources

guideline_position; exposure_boundaryEXT-113 · Not formally appraised
Clinical Practice Guideline on the Management of Stimulant Use DisorderG-ASAM-STUD · Final 2023; journal 2024 · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-169
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-027Module C

Provisional public source

No medication is FDA-approved for cannabis-use disorder, and nonpregnant candidate-drug studies do not justify replacing cannabis with NAC, prescription cannabinoids, nabiximols, or prescription CBD during pregnancy.

indication_boundaryPregnancyNew initiation

Public-source certainty descriptor: Moderate consensus; very low pregnancy drug evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate consensus; very low pregnancy drug evidence
Comparator: Candidate medication versus psychosocial CUD care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No established pregnancy efficacy

Limitations

Products differ in standardization and indication; CUD trials excluded pregnancy

Public-source disposition — not a commissioned recommendation

Use psychosocial treatment; do not initiate candidate medicines as pregnancy CUD treatment

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

indication_boundary; guideline_and_observational_safetyEXT-115 · Not formally appraised
regulator_positionEXT-132 · Not formally appraised

Citation controls

PMID: 40966737
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-170
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-028Module C

Provisional public source

N-acetylcysteine has inconsistent nonpregnant CUD efficacy; obstetric use for other indications does not establish benefit for CUD or routine psychiatric use.

indication_boundaryPregnancyNew initiationUnplanned exposure

Public-source certainty descriptor: Low and indirect
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low and indirect
Comparator: NAC versus psychosocial care/placebo
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy CUD effect estimate

Limitations

Supplement identity and dose vary; indication transfer is invalid

Public-source disposition — not a commissioned recommendation

Do not initiate for CUD in pregnancy; evaluate an actual exposure by product and indication

Open sources, mapped records, and appraisal controls

Mapped medication records

N-acetylcysteineMED-242

Linked sources

indication_boundary; guideline_and_observational_safetyEXT-115 · Not formally appraised
regulator_positionEXT-132 · Not formally appraised

Citation controls

PMID: 40966737
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-171
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-029Module C

Provisional public source

Dronabinol, nabilone, nabiximols and Epidiolex are distinct standardized cannabinoid products; none should be treated as evidence that consumer cannabis or CBD is safe or effective in pregnancy.

formulation_boundaryPregnancy and lactationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: High product-identity certainty; low reproductive evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High product-identity certainty; low reproductive evidence
Comparator: Prescription/authorized products versus consumer THC/CBD
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Not applicable

Limitations

Each product has different THC/CBD content, route, label and jurisdiction

Public-source disposition — not a commissioned recommendation

Verify exact product; generally avoid CUD initiation and make indication-specific decisions

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

formulation_boundaryEXT-116 · Not formally appraised
regulator_positionEXT-132 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-172
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-030Module C

Provisional public source

Flumazenil can precipitate seizures and acute withdrawal in chronic benzodiazepine exposure or mixed overdose and is not a routine benzodiazepine-withdrawal treatment.

emergency_safetyAcute overdose or withdrawalUnplanned exposure

Public-source certainty descriptor: High clinical consensus; low pregnancy-specific evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High clinical consensus; low pregnancy-specific evidence
Comparator: Flumazenil versus supportive airway/ventilation care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy comparative estimate; established mechanistic and clinical seizure risk

Limitations

Selected iatrogenic oversedation may be different; co-ingestants and seizure history matter

Public-source disposition — not a commissioned recommendation

Reserve for carefully selected acute-care use with toxicology and seizure capability; taper dependence gradually

Open sources, mapped records, and appraisal controls

Mapped medication records

FlumazenilMED-247

Linked sources

emergency_safetyEXT-117 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-318E6A2FF521 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-173
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-031Module C

Provisional public source

Benztropine and trihexyphenidyl can treat acute dystonia or drug-induced parkinsonism, but they are not treatments for tardive dyskinesia and anticholinergics may worsen TD.

indication_boundaryPregnancy and postpartumDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate nonpregnant clinical consensus; very low reproductive evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate nonpregnant clinical consensus; very low reproductive evidence
Comparator: Anticholinergic use for correct phenotype versus TD use
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy outcome estimate

Limitations

Sparse pregnancy/lactation data; emergency laryngeal dystonia is a different risk context

Public-source disposition — not a commissioned recommendation

Confirm movement phenotype; treat airway-threatening dystonia promptly; avoid chronic anticholinergic treatment for TD

Open sources, mapped records, and appraisal controls

Mapped medication records

BenztropineMED-248
TrihexyphenidylMED-249

Linked sources

indication_boundaryEXT-118 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-7744F6FEDCC7 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-174
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-032Module C

Provisional public source

Human pregnancy and infant-outcome evidence for valbenazine, deutetrabenazine and tetrabenazine is essentially absent; nonpregnant TD efficacy does not establish fetal or lactation safety.

evidence_gapPregnancy and lactationStable continuationNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low reproductive certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low reproductive certainty
Comparator: VMAT2 inhibitor exposure versus unexposed
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate human pregnancy cohorts

Limitations

Labels rely heavily on animal data; untreated severe TD can itself impair nutrition and function

Public-source disposition — not a commissioned recommendation

Avoid new initiation when feasible; individualize severe continuation and separate lactation plan

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

evidence_gap; label_lactationEXT-119 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-F5319172F32F · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-175
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-033Module C

Provisional public source

Valbenazine labeling advises no breastfeeding during treatment and for five days after the final dose.

label_lactationLactationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: High label certainty; no direct infant-outcome evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High label certainty; no direct infant-outcome evidence
Comparator: Breastfeeding versus temporary interruption/alternative treatment
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Five-day interval after final dose

Limitations

Label precaution is based on absence/animal milk data rather than observed human infant harm

Public-source disposition — not a commissioned recommendation

Follow exact current label and preserve milk supply/feeding plan if treatment is essential

Open sources, mapped records, and appraisal controls

Mapped medication records

ValbenazineMED-250

Linked sources

evidence_gap; label_lactationEXT-119 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-176
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-034Module C

Provisional public source

Accumulated early pregnancy experience with bromocriptine and cabergoline for prolactinoma has not shown a clear major adverse pattern, but psychiatric antipsychotic-induced hyperprolactinemia is a different indication and usually permits alternatives.

indication_and_safetyPericonception and early pregnancySwitch before conceptionUnplanned exposure

Public-source certainty descriptor: Moderate-low; accumulated observational series
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate-low; accumulated observational series
Comparator: Dopamine agonist exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single causal estimate used

Limitations

Cabergoline exposure base is smaller; macroadenoma threat changes benefit-risk

Public-source disposition — not a commissioned recommendation

For prolactinoma use endocrine guidance; for psychiatric adverse effect first review antipsychotic strategy and confirm cause

Open sources, mapped records, and appraisal controls

Mapped medication records

BromocriptineMED-253
CabergolineMED-254

Linked sources

indication_and_safetyEXT-120 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-4505D5856FF5 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-177
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-035Module C

Provisional public source

Bromocriptine and cabergoline lower prolactin and can suppress milk production; routine postpartum suppression of physiologic lactation is not recommended in current labeling.

lactation_safetyEarly postpartumUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: High pharmacologic and label certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High pharmacologic and label certainty
Comparator: Dopamine agonist versus no suppression
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No infant exposure estimate needed to establish lactation suppression

Limitations

A threatening macroadenoma may justify treatment despite feeding goals; postpartum vascular events underpin warnings

Public-source disposition — not a commissioned recommendation

Do not use routinely to suppress lactation; make specialist plan if disease treatment is required

Open sources, mapped records, and appraisal controls

Mapped medication records

BromocriptineMED-253
CabergolineMED-254

Linked sources

lactation_safetyEXT-121 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-0EA02CB24551 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-178
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-036Module C

Provisional public source

Memantine evidence for catatonia is largely case reports and series; benzodiazepines and ECT remain established first-line pathways.

indication_boundaryPregnancy and postpartum catatoniaNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: Very low for memantine; moderate guideline consensus for first-line care
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low for memantine; moderate guideline consensus for first-line care
Comparator: Memantine adjunct versus lorazepam/ECT pathway
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No controlled pregnancy efficacy estimate

Limitations

Catatonia etiologies and severity vary; memantine pregnancy/milk data are inadequate

Public-source disposition — not a commissioned recommendation

Do not delay lorazepam/ECT assessment; consider memantine only as specialist adjunct in refractory cases

Open sources, mapped records, and appraisal controls

Mapped medication records

MemantineMED-255

Linked sources

indication_boundaryEXT-122 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-402E9F35D80E · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-179
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-037Module C

Provisional public source

NMS is an emergency whose core treatment is stopping the dopamine blocker and intensive supportive care; dantrolene evidence is case-based and its malignant-hyperthermia pregnancy label cannot prove NMS efficacy.

emergency_guidanceAcute NMSClinical-position linkage pending

Public-source certainty descriptor: Low for dantrolene efficacy; high emergency consensus
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low for dantrolene efficacy; high emergency consensus
Comparator: Supportive care with or without dantrolene
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No randomized NMS pregnancy treatment effect

Limitations

Case severity and co-treatment confound outcomes; formulation labels differ

Public-source disposition — not a commissioned recommendation

Stop culprit and escalate to ICU-obstetric care; reserve dantrolene for selected severe/refractory cases

Open sources, mapped records, and appraisal controls

Mapped medication records

DantroleneMED-256

Linked sources

emergency_guidanceEXT-123 · Not formally appraised
label_lactationEXT-124 · Not formally appraised

Citation controls

PMID: 32659853
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-180
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-038Module C

Provisional public source

The RYANODEX label advises no breastfeeding during treatment and for three days after the final dose.

label_lactationLactation after acute treatmentDelivery/postpartum/lactation

Public-source certainty descriptor: High label certainty; no robust infant-outcome evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High label certainty; no robust infant-outcome evidence
Comparator: Breastfeeding versus temporary interruption
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Three-day interval after final dose

Limitations

Applies to the exact product label; acute maternal condition may independently preclude feeding

Public-source disposition — not a commissioned recommendation

Follow current product label and support a temporary feeding/milk-supply plan

Open sources, mapped records, and appraisal controls

Mapped medication records

DantroleneMED-256

Linked sources

label_lactationEXT-124 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-181
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-039Module C

Provisional public source

Metformin has direct evidence for antipsychotic-associated weight prevention/treatment in nonpregnant adults and extensive pregnancy experience for metabolic indications, but no direct pregnancy trial establishes benefit for psychotropic-weight mitigation.

indication_boundaryPreconception and pregnancyStable continuationNew initiationSwitch before conception

Public-source certainty descriptor: Moderate for nonpregnant weight outcome; indirect for pregnancy indication
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate for nonpregnant weight outcome; indirect for pregnancy indication
Comparator: Metformin plus monitoring versus lifestyle/antipsychotic change
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy psychiatric-weight effect estimate

Limitations

Placental transfer and long-term offspring metabolic outcomes remain under study; renal function/B12/GI effects matter

Public-source disposition — not a commissioned recommendation

May continue for a valid metabolic indication; initiation solely for psychotropic weight in pregnancy requires individualized rationale

Open sources, mapped records, and appraisal controls

Mapped medication records

MetforminMED-257

Linked sources

indication_boundaryEXT-125 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-DED86BAE088D · Unverified metadata

Citation controls

PMID: 39657713
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-182
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-040Module C

Provisional public source

Metformin labeling describes low transfer into human milk, approximately 0.11% to 1% of the maternal weight-adjusted dose in small studies.

lactation_pharmacokineticsLactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate-low; small pharmacokinetic studies
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate-low; small pharmacokinetic studies
Comparator: Infant exposure through milk versus maternal dose
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Relative infant dose approximately 0.11% to 1%

Limitations

Small infant samples and limited clinical follow-up; formulation and maternal renal function matter

Public-source disposition — not a commissioned recommendation

Generally compatible when indicated; monitor unusually vulnerable infants and maternal renal status

Open sources, mapped records, and appraisal controls

Mapped medication records

MetforminMED-257

Linked sources

lactation_pharmacokineticsEXT-126 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-183
Required tool: ROBINS-E
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-041Module C

Provisional public source

Observational early-pregnancy GLP-1 receptor agonist cohorts have not shown a clear major-congenital-malformation increase versus insulin or selected comparators, but are too limited to support continuation for weight loss or psychiatric metabolic mitigation.

comparative_safetyPericonception and early pregnancyStable continuationUnplanned exposure

Public-source certainty descriptor: Low-to-moderate; observational and indication-confounded
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low-to-moderate; observational and indication-confounded
Comparator: GLP-1 exposure versus insulin or nonexposed comparator
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No greater MCM risk observed in studied cohorts; estimates remain imprecise

Limitations

Mostly diabetes exposures, early windows, few molecule-specific cases; live-birth selection possible

Public-source disposition — not a commissioned recommendation

Reassure after inadvertent early exposure without claiming zero risk; generally discontinue weight-loss use when pregnancy is recognized

Open sources, mapped records, and appraisal controls

Mapped medication records

GLP-1 receptor agonistsMED-258

Linked sources

comparative_safetyEXT-127 · Not formally appraised
label_and_formulationEXT-128 · Not formally appraised

Citation controls

PMID: 38079178
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-184
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-042Module C

Provisional public source

Semaglutide labeling advises stopping at least two months before a planned pregnancy; pregnancy and lactation recommendations are molecule- and formulation-specific and must not be generalized across the GLP-1 class.

label_and_formulationPreconception, pregnancy, and lactationStable continuationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: High label certainty; low class-wide reproductive certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High label certainty; low class-wide reproductive certainty
Comparator: Semaglutide versus other GLP-1 products
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Two-month preconception interval for semaglutide

Limitations

Long half-life and oral absorption enhancer matter; labels change and differ by product/indication

Public-source disposition — not a commissioned recommendation

Plan molecule-specific preconception discontinuation; check exact current label for pregnancy and breastfeeding

Open sources, mapped records, and appraisal controls

Mapped medication records

GLP-1 receptor agonistsMED-258

Linked sources

label_and_formulationEXT-128 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-185
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-043Module C

Provisional public source

Nuedexta has no adequate human pregnancy data; quinidine adds QT prolongation and CYP2D6 interactions, and the combination can contribute to serotonin toxicity.

label_safetyPregnancy and lactationNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Very low reproductive evidence; high interaction certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low reproductive evidence; high interaction certainty
Comparator: Dextromethorphan/quinidine versus alternative management
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No human pregnancy risk estimate

Limitations

Animal findings do not quantify human risk; quinidine is in milk but combination infant data are inadequate

Public-source disposition — not a commissioned recommendation

Verify pseudobulbar-affect indication; avoid new off-label psychiatric initiation and review ECG/interactions

Open sources, mapped records, and appraisal controls

Mapped medication records

Dextromethorphan hydrobromide/quinidine sulfateMED-259

Linked sources

label_safetyEXT-129 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-186
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-044Module C

Provisional public source

Donepezil, rivastigmine and galantamine have inadequate human pregnancy and lactation outcome data; nonpregnant cognitive efficacy does not establish perinatal benefit.

evidence_gapPregnancy and lactationStable continuationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Very low reproductive certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low reproductive certainty
Comparator: Cholinesterase inhibitor versus nonpharmacologic or alternative care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate comparative pregnancy cohorts

Limitations

Diseases requiring these drugs during reproductive years are uncommon; bradycardia, syncope, vomiting and weight loss affect maternal risk

Public-source disposition — not a commissioned recommendation

Avoid new off-label psychiatric use; individualize a stable essential neurologic indication

Open sources, mapped records, and appraisal controls

Mapped medication records

DonepezilMED-260
RivastigmineMED-261
GalantamineMED-262

Linked sources

evidence_gapEXT-130 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-613259423C9F · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-187
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-045Module C

Provisional public source

Tacrine is an obsolete cholinesterase inhibitor with important hepatotoxicity and no useful reproductive evidence.

regulatory_and_safetyPreconception through lactationNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: High hepatotoxicity certainty; very low reproductive evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High hepatotoxicity certainty; very low reproductive evidence
Comparator: Tacrine versus currently available alternatives
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable pregnancy outcome estimate

Limitations

Legacy use is rare and market status varies

Public-source disposition — not a commissioned recommendation

Do not initiate; transition any unexpected legacy use under specialist supervision

Open sources, mapped records, and appraisal controls

Mapped medication records

TacrineMED-263

Linked sources

regulatory_and_safetyEXT-131 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-188
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-046Module C

Provisional public source

ACOG recommends cessation of cannabis in pregnancy and lactation; observational studies associate prenatal cannabis with preterm birth, impaired growth and NICU admission, but confounding and exposure measurement limit causal estimates.

guideline_and_observational_safetyPregnancy and lactationSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate guideline consensus; low-to-moderate observational certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate guideline consensus; low-to-moderate observational certainty
Comparator: Cannabis exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single pooled causal estimate adopted

Limitations

THC potency, route, tobacco/polysubstance use and socioeconomic factors vary; no specific defect pattern established

Public-source disposition — not a commissioned recommendation

Encourage cessation; treat the symptom/condition with established alternatives; use nonpunitive shared decision-making

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

indication_boundary; guideline_and_observational_safetyEXT-115 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-5B3F77CDA12F · Unverified metadata

Citation controls

PMID: 40966737
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-189
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-047Module C

Provisional public source

FDA advises against THC, marijuana and CBD in any form during pregnancy or breastfeeding; consumer CBD may contain THC, contaminants or inaccurate amounts and is not equivalent to prescription cannabidiol.

regulator_positionPregnancy and lactationStable continuationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: High regulator-position certainty; very low product-specific evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High regulator-position certainty; very low product-specific evidence
Comparator: Consumer cannabinoid product versus no use or standardized medicine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable consumer-product dose or infant exposure estimate

Limitations

Product composition and route are often unknown; topical exposure differs but does not establish safety

Public-source disposition — not a commissioned recommendation

Recommend discontinuation; if lactation use continues, reduce exposure and address smoke, impairment, bed-sharing and storage

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

regulator_positionEXT-132 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-190
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-048Module C

Provisional public source

Kratom is not FDA-approved for OUD, withdrawal, pain or psychiatric illness; dependence occurs and prolonged prenatal exposure has produced opioid-like neonatal withdrawal in case reports.

safety_signal_and_regulatoryPregnancy and neonatal periodStable continuationNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low for incidence; high nonapproval certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low for incidence; high nonapproval certainty
Comparator: Kratom exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Case reports; no incidence estimate

Limitations

Products vary in alkaloids and may contain concentrated 7-hydroxymitragynine, microbes or metals; co-use confounds

Public-source disposition — not a commissioned recommendation

Do not initiate or continue casually; assess dependence and transition without abandonment or abrupt unmanaged withdrawal

Open sources, mapped records, and appraisal controls

Mapped medication records

KratomMED-266

Linked sources

safety_signal_and_regulatoryEXT-133 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-DFDA0001078B · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-191
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-049Module C

Provisional public source

St. John's wort, valerian, kava, ashwagandha, saffron and oral lavender lack adequate product-specific pregnancy and lactation evidence; nonpregnant extract studies do not validate retail products.

evidence_gapPregnancy and lactationNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low product-specific certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low product-specific certainty
Comparator: Botanical product versus established psychiatric treatment
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate comparative pregnancy effectiveness data

Limitations

Species, extraction, dose, mixtures, contaminants and lot variation undermine extrapolation

Public-source disposition — not a commissioned recommendation

Avoid new initiation for psychiatric treatment; photograph label, check interactions, and counsel without predicting harm after isolated exposure

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

evidence_gap; formulation_boundaryEXT-134 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-1760B9AB2B13 · Unverified metadata

Citation controls

PMID: 28511598
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-192
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-050Module C

Provisional public source

St. John's wort has major CYP/P-glycoprotein and serotonergic interactions, kava has a serious liver-injury signal, and NCCIH advises avoiding ashwagandha in pregnancy and breastfeeding.

interaction_and_safetyPreconception through lactationStable continuationNew initiationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate for interactions/liver signal; low reproductive outcome evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate for interactions/liver signal; low reproductive outcome evidence
Comparator: Use versus avoidance/established care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No pregnancy causal effect estimate

Limitations

Retail composition varies; recommendations are not based on large pregnancy cohorts

Public-source disposition — not a commissioned recommendation

Avoid initiation; discontinue under medication review and assess liver or serotonin symptoms when relevant

Open sources, mapped records, and appraisal controls

Mapped medication records

St. John’s wortMED-267
KavaMED-269
AshwagandhaMED-270

Linked sources

interaction_and_safetyEXT-135 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-538C3DFA3F15 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-193
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-051Module C

Evidence gap

Valerian, concentrated saffron supplements and oral lavender preparations have insufficient pregnancy and lactation evidence; culinary saffron or lavender aroma exposure is not equivalent to a concentrated oral extract.

formulation_boundaryPregnancy and lactationNew initiationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low direct certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low direct certainty
Comparator: Concentrated oral product versus ordinary food/aroma exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable effect estimate

Limitations

Commercial extracts and doses differ; absence of a signal is not proof of safety

Public-source disposition — not a commissioned recommendation

Avoid new psychiatric initiation; provide routine exposure review unless symptoms or adulterants warrant more

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

evidence_gap; formulation_boundaryEXT-134 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-55A529982941 · Unverified metadata

Citation controls

PMID: 28511598
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-194
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-052Module C

Provisional public source

Folic acid 400 to 800 micrograms daily is the usual periconceptional neural-tube-defect prevention range; 4,000 micrograms daily is reserved for defined high-risk situations under clinical guidance and is not evidence-based psychiatric augmentation.

dose_and_indication_boundaryPreconception and early pregnancySwitch before conception

Public-source certainty descriptor: High for obstetric prevention; low for psychiatric augmentation
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High for obstetric prevention; low for psychiatric augmentation
Comparator: Obstetric prevention dose versus high-dose psychiatric supplement
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

400 to 800 micrograms/day usual; 4,000 micrograms/day selected high risk

Limitations

High-risk definitions vary by guideline; total intake and B12 status matter

Public-source disposition — not a commissioned recommendation

Use the indicated obstetric dose; do not add high-dose folate for mood without a specific rationale

Open sources, mapped records, and appraisal controls

Mapped medication records

Folate/high-dose folic acid productsMED-273

Linked sources

dose_and_indication_boundaryEXT-136 · Not formally appraised
public-health guidance and evidence gapEXT-051 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-195
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-053Module C

Provisional public source

Inositol, omega-3 and magnesium have nutritional or metabolic contexts, but pregnancy use for those purposes does not prove efficacy for depression, anxiety or insomnia.

indication_boundaryPregnancy and postpartumSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Low for psychiatric efficacy; moderate nutritional guidance
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low for psychiatric efficacy; moderate nutritional guidance
Comparator: Nutritional/metabolic use versus psychiatric treatment
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

A 2024 pregnancy supplement study did not improve maternal mood/anxiety

Limitations

Products, combinations and endpoints vary; nutritional deficiency is a different indication

Public-source disposition — not a commissioned recommendation

Meet nutritional needs and correct deficiency; do not substitute supplements for effective psychiatric care

Open sources, mapped records, and appraisal controls

Mapped medication records

InositolMED-274
Omega-3 fatty acid productsMED-275
Magnesium products marketed for sleep/anxietyMED-278

Linked sources

indication_boundaryEXT-137 · Not formally appraised
public-health guidance and evidence gapEXT-051 · Not formally appraised

Citation controls

PMID: 38402742
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-196
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-054Module C

Provisional public source

High-dose L-tryptophan and 5-HTP lack adequate pregnancy treatment evidence and can add serotonergic toxicity risk with antidepressants, MAO inhibitors, tramadol, dextromethorphan or MDMA.

interaction_and_evidence_gapPregnancy and lactationNew initiationDelivery/postpartum/lactation

Public-source certainty descriptor: Very low reproductive evidence; moderate mechanistic interaction certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low reproductive evidence; moderate mechanistic interaction certainty
Comparator: Supplement use versus avoidance/established care
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable pregnancy efficacy or safety estimate

Limitations

Product contamination and dose uncertainty; normal dietary tryptophan is not equivalent

Public-source disposition — not a commissioned recommendation

Avoid psychiatric high-dose initiation; assess for serotonin toxicity after combinations

Open sources, mapped records, and appraisal controls

Mapped medication records

L-tryptophanMED-276
5-hydroxytryptophanMED-277

Linked sources

interaction_and_evidence_gapEXT-138 · Not formally appraised
regulatory_boundaryEXT-139 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-197
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-055Module C

Provisional public source

US dietary supplements are not FDA-approved for safety and effectiveness before marketing; label identity, purity and consistency cannot be assumed.

regulatory_boundaryAll reproductive windowsClinical-position linkage pending

Public-source certainty descriptor: High regulatory certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High regulatory certainty
Comparator: Retail supplement versus standardized approved medicine
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Not applicable

Limitations

Some products follow quality programs, but that does not establish pregnancy effectiveness or safety

Public-source disposition — not a commissioned recommendation

Record brand, ingredients, dose and lot; check interactions/contaminants; avoid categorical reassurance

Open sources, mapped records, and appraisal controls

Mapped medication records

St. John’s wortMED-267
ValerianMED-268
KavaMED-269
AshwagandhaMED-270
SaffronMED-271
Lavender oral preparationMED-272
Folate/high-dose folic acid productsMED-273
InositolMED-274
Omega-3 fatty acid productsMED-275
L-tryptophanMED-276
5-hydroxytryptophanMED-277
Magnesium products marketed for sleep/anxietyMED-278

Linked sources

regulatory_boundaryEXT-139 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-79EEBF3D75A3 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-198
Required tool: Regulatory-source verification
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-056Module C

Provisional public source

ACOG states that caffeine intake below 200 mg/day does not appear to be a major contributor to miscarriage or preterm birth, while growth effects and higher intake remain uncertain.

guideline_positionPregnancyClinical-position linkage pending

Public-source certainty descriptor: Moderate guideline consensus; observational evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate guideline consensus; observational evidence
Comparator: Lower caffeine intake versus higher/no intake
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Below 200 mg/day

Limitations

Self-reported intake and confounding limit thresholds; all sources must be counted

Public-source disposition — not a commissioned recommendation

Keep total intake below 200 mg/day; taper gradually if reducing substantial habitual use

Open sources, mapped records, and appraisal controls

Mapped medication records

Concentrated caffeine and energy productsMED-279

Linked sources

guideline_positionEXT-140 · Not formally appraised

Citation controls

PMID: 20664420
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-199
Required tool: AGREE II
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-057Module C

Provisional public source

Pure and highly concentrated caffeine powders/liquids can cause lethal dosing errors and are qualitatively different from coffee or tea.

emergency_safetyAcute exposureUnplanned exposure

Public-source certainty descriptor: High regulator warning; no controlled pregnancy data
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: High regulator warning; no controlled pregnancy data
Comparator: Concentrated caffeine versus ordinary dietary beverages
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

FDA reports severe toxicity and deaths; no pregnancy-specific dose threshold

Limitations

Product concentration and measuring tools vary

Public-source disposition — not a commissioned recommendation

Avoid entirely; seek emergency care for palpitations, severe agitation, vomiting, hyperthermia, syncope or seizure

Open sources, mapped records, and appraisal controls

Mapped medication records

Concentrated caffeine and energy productsMED-279

Linked sources

emergency_safetyEXT-141 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-200
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-058Module C

Provisional public source

Nonmedical stimulants can cause severe hypertension, ischemia, arrhythmia, stroke, hyperthermia, seizure and psychosis; pregnancy cohorts associate exposure with growth restriction, preterm birth and placental complications, especially cocaine-related abruption.

maternal_and_pregnancy_safetyAcute and chronic pregnancy exposureUnplanned exposure

Public-source certainty descriptor: Moderate for acute toxidrome; low-to-moderate observational pregnancy certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate for acute toxidrome; low-to-moderate observational pregnancy certainty
Comparator: Nonmedical stimulant exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No single causal estimate adopted

Limitations

Dose, route, tobacco/alcohol/other drugs, poverty, trauma and prenatal-care access confound outcomes; congenital findings are inconsistent

Public-source disposition — not a commissioned recommendation

Treat acute symptoms urgently; provide nonpunitive prenatal/addiction care and do not wait for abstinence

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

maternal_and_pregnancy_safetyEXT-142 · Not formally appraised
Clinical Practice Guideline on the Management of Stimulant Use DisorderG-ASAM-STUD · Final 2023; journal 2024 · Current

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-201
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-059Module C

Provisional public source

ABM advises avoiding breastfeeding during active nonprescribed stimulant use; a nonpunitive plan can support pumping and later reassessment when clinically appropriate.

lactation_positionLactationStable continuationSwitch before conceptionDelivery/postpartum/lactation

Public-source certainty descriptor: Moderate protocol consensus; low direct infant-outcome evidence
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Moderate protocol consensus; low direct infant-outcome evidence
Comparator: Breastfeeding during active use versus temporary alternative feeding
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No universal time-to-clearance estimate across products

Limitations

Unknown dose, adulterants, infant age, route and co-use prevent a single interval; prescribed stimulants are a different question

Public-source disposition — not a commissioned recommendation

Avoid breastfeeding during active nonprescribed use; create individualized return-to-feeding and relapse-prevention plan

Open sources, mapped records, and appraisal controls

Mapped medication records

Linked sources

lactation_positionEXT-143 · Not formally appraised

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-202
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-060Module C

Provisional public source

No adequate human studies establish psilocybin pregnancy or lactation safety, miscarriage risk, malformation risk, neurodevelopment, or milk transfer.

evidence_gapPregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low
Comparator: Psilocybin exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No adequate comparative human data

Limitations

Mushroom identity, co-ingestants and setting vary; trial populations exclude pregnancy

Public-source disposition — not a commissioned recommendation

Avoid use; after isolated exposure assess symptoms/product identity and do not recommend termination or special testing solely from the exposure

Open sources, mapped records, and appraisal controls

Mapped medication records

PsilocybinMED-283

Linked sources

evidence_gapEXT-144 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-3895F1960A39 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-203
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-061Module C

Provisional public source

Small, confounded MDMA pregnancy reports are inadequate to establish a defect or neurodevelopmental pattern; acute hyperthermia, hyponatremia, serotonin toxicity and adulterants are immediate hazards.

safety_signal_and_evidence_gapPregnancy and acute exposureUnplanned exposure

Public-source certainty descriptor: Very low reproductive certainty; high acute-toxicity certainty
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low reproductive certainty; high acute-toxicity certainty
Comparator: MDMA exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable causal pregnancy estimate

Limitations

Small samples and polysubstance confounding; investigational therapy results do not establish pregnancy safety

Public-source disposition — not a commissioned recommendation

Avoid use; urgently treat toxicity; use established PTSD/psychiatric care

Open sources, mapped records, and appraisal controls

Mapped medication records

MidomafetamineMED-284

Linked sources

safety_signal_and_evidence_gapEXT-145 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-25A579C4F1DA · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-204
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-062Module C

Provisional public source

Old small studies and case reports of LSD do not establish a congenital-defect pattern, but pregnancy, neurodevelopment and lactation evidence remain inadequate.

evidence_gapPregnancy and lactationUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Very low
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Very low
Comparator: LSD exposure versus no exposure
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

No reliable causal estimate

Limitations

Historical exposure ascertainment and co-use are poor; acute trauma, panic or psychosis may dominate risk

Public-source disposition — not a commissioned recommendation

Avoid use; provide supportive acute care and do not infer a specific fetal defect after isolated exposure

Open sources, mapped records, and appraisal controls

Mapped medication records

Lysergic acid diethylamideMED-285

Linked sources

evidence_gapEXT-146 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-3F2688299678 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-205
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.

C-063Module C

Provisional public source

Ibogaine has no adequate pregnancy evidence and has caused QT prolongation, ventricular arrhythmia, cardiac arrest, seizure and death in case reports; it is not a safe unsupervised OUD detoxification substitute.

emergency_safetyAcute exposure, pregnancy, and postpartumSwitch before conceptionUnplanned exposureDelivery/postpartum/lactation

Public-source certainty descriptor: Low for incidence; high seriousness of signal
Formal GRADE field: Not assessed. Public-source certainty descriptor retained for context only: Low for incidence; high seriousness of signal
Comparator: Ibogaine versus evidence-based MOUD
Absolute-risk field: Pending primary-source absolute-risk extraction and calculation check

Effect or numbers carried forward

Case reports; no incidence estimate

Limitations

Product purity, dose, co-use and medical screening vary; publication bias prevents incidence estimation

Public-source disposition — not a commissioned recommendation

Strongly avoid; after exposure obtain ECG/electrolytes and urgent toxicology/cardiology care for symptoms; transition OUD to evidence-based treatment

Open sources, mapped records, and appraisal controls

Mapped medication records

IbogaineMED-286

Linked sources

emergency_safetyEXT-147 · Not formally appraised
claim- or inventory-linked URL; title not extractedURL-3F2688299678 · Unverified metadata

Citation controls

PMID: Not populated in v0.95
DOI: Pending DOI verification
Exact locator: Pending exact table/figure/page/supplement locator
Publication date: Pending publication-date verification
Access date: 2026-07-29
Correction / retraction check: Same-day source surveillance recorded; source-by-source correction/retraction verification remains pending

Appraisal controls

Appraisal ID: APP-206
Required tool: Design classification pending
Current state: Not started — full text and independent appraisal pending
First assessor: Pending named assessor
Second assessor: Pending independent assessor
Next action: Obtain eligible full text; classify design; complete tool independently twice; adjudicate; link judgment and rationale to claim ledger.