# Vitamin B6: pyridoxine monotherapy × Reduced nausea severity in early pregnancy

Verdict 3096 · Evidence Check

Stored-material review date: 2026-10-05  
Original evidence date: 2026-09-15  
Review-criteria version: NGM-v3096-ORAL-PYRIDOXINE-EARLY-PREGNANCY-NAUSEA-1.1  
Public page/material preparation date: 2026-11-01

Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect.

## Assessment scope

- Population: Patients with nausea in early pregnancy; exact gestational weeks, diagnostic criteria, severity criteria, and inpatient status are unverified. The severe-nausea subgroup is kept separate from the overall group, and the findings are not generalized to hyperemesis gravidarum.
- Ingredient, formulation and route: Vitamin B6 as pyridoxine alone · a single-ingredient oral preparation; hydrochloride identity, tablet/capsule form, release type, and excipients are unverified
- Dose: Main regimen: 25 mg every 8 hours; schedule-derived 75 mg/day; actual total intake and adherence are unverified. The supportive trial at 30 mg/day is separate.
- Comparator: Placebo; composition, common care, concomitant treatment, and rescue medication are unverified. Doxylamine combinations are not included.
- Measured outcome: Between-group difference in nausea scores. The exact instrument, range, unit, assessment day, and endpoint hierarchy are unverified; not relabeled as a PUQE total.
- Duration: The retained record describes a short-term trial; exact treatment days, assessment day, and follow-up duration are unverified
- Questions outside this scope: PMS 3095, historical composite 127, doxylamine/ginger/prenatal combinations, other B6 forms/salts, PUQE, vomiting, hyperemesis gravidarum, fetal/birth events, and optimal dose/maintenance effects are separate.

## Checklist items

### N01 · Which nausea comparison is addressed?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: A single main claim of reduced nausea severity in early pregnancy was selected. The original claim_count=1, and there is no subclaims key.
- Why unverified: Confirming the identity of the question and demonstrating efficacy are separate matters.
- Reason for missing information: Confirming the identity of the question and demonstrating efficacy are separate matters.
- Required materials and conditions: Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity
- Materials to obtain first: Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity
- Further research: Compare the population, intervention, and endpoint boundaries in the manuscript and trial results separately.
- Conditions for verification: Link the exact original wording of the effect claim to the inclusion and exclusion boundaries.
- Why this condition is needed: Needed to keep different pregnancy-related effects from being combined into a single efficacy claim.
- Application exceptions: Vomiting, PUQE totals, hyperemesis gravidarum, PMS, and combination products are separate.
- Remaining uncertainty: Confirming the identity of the question and demonstrating efficacy are separate matters.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed; M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed
- Related sources: S01, S02

### N02 · Is this the same question as 127·3095?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The current related_records distinguishes 127 as the historical PMS+pregnancy nausea composite and 3095 as a separate PMS-only claim.
- Why unverified: This is a reading of relationship metadata, not a review of the full related manuscripts.
- Reason for missing information: This is a reading of relationship metadata, not a review of the full related manuscripts.
- Required materials and conditions: Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim
- Materials to obtain first: Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim
- Further research: If follow-up is authorized, compare the exact questions in the related authoritative versions to check for duplication.
- Conditions for verification: Preserve the distinctions recorded in the current relationship object and the limitation that the underlying texts were not read.
- Why this condition is needed: Needed to keep related record numbers from being combined as the same study or the same efficacy claim.
- Application exceptions: The related manuscripts and ZIP archives were not newly opened in this review.
- Remaining uncertainty: This is a reading of relationship metadata, not a review of the full related manuscripts.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed; distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a case-specific application
- Related sources: S01, S03

### N03 · Have the actual substance and salt been verified?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Recorded as oral pyridoxine monotherapy, but hydrochloride identity is unverified. It is not automatically equivalent to pyridoxal or PLP.
- Why unverified: Verification of the exact salt remains outstanding.
- Reason for missing information: Verification of the exact salt remains outstanding.
- Required materials and conditions: Pyridoxine and the exact salt, active ingredient, and route
- Materials to obtain first: Pyridoxine and the exact salt, active ingredient, and route
- Further research: Link composition and quality documents to the results for the relevant trial arm.
- Conditions for verification: Record verified pyridoxine identity separately from the unverified salt.
- Why this condition is needed: Needed to prevent findings for PLP or combination products from being repurposed under the name vitamin B6.
- Application exceptions: Do not assume whether it is hydrochloride.
- Remaining uncertainty: Verification of the exact salt remains outstanding.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application
- Related sources: S01, S07

### N04 · Are the manufacturing origin, manufacturer, and dosage form known?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Manufacturing origin, manufacturer, purity, batch, tablet/capsule, release type, and excipients are unverified within the retained materials.
- Why unverified: This does not mean that the information is absent from the original paper as a whole.
- Reason for missing information: This does not mean that the information is absent from the original paper as a whole.
- Required materials and conditions: Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients
- Materials to obtain first: Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients
- Further research: Compare batch and formulation documents with administration records to verify actual exposure.
- Conditions for verification: Identify separately only the items verified in the directly studied preparation.
- Why this condition is needed: Needed to prevent the single-ingredient dosage form in the question from being mistaken for actual product specifications.
- Application exceptions: Do not assign the composition of a doxylamine product to the preparation being directly assessed.
- Remaining uncertainty: This does not mean that the information is absent from the original paper as a whole.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed
- Related sources: S01, S02

### N05 · Are 25 mg every 8 hours and actual total exposure the same?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The main regimen of 25 mg every 8 hours and the original schedule arithmetic of 75 mg/day were preserved. The actual dose taken, total intake, and adherence are unverified.
- Why unverified: Do not use 75 as the actual amount taken or a personally recommended dose.
- Reason for missing information: Do not use 75 as the actual amount taken or a personally recommended dose.
- Required materials and conditions: Nominal dose, interval, actual intake, concurrent B6, and adherence
- Materials to obtain first: Nominal dose, interval, actual intake, concurrent B6, and adherence
- Further research: Obtain administration, medication-taking, and concurrent supplementation records by arm to verify total exposure.
- Conditions for verification: Preserve the nominal regimen, historical arithmetic, and actual total exposure separately.
- Why this condition is needed: Needed to prevent schedule arithmetic from being treated as actual intake or a recommended dose.
- Application exceptions: 75 mg/day quotes the schedule arithmetic in the manuscript; it is not newly calculated.
- Remaining uncertainty: Do not use 75 as the actual amount taken or a personally recommended dose.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom-designed
- Related sources: S01

### N06 · Are the number of treatment days and the outcome assessment day known?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The retained description refers to a short-term trial, but the exact treatment days, assessment day, and follow-up duration are unverified.
- Why unverified: No new common duration threshold, such as 12 weeks, was set.
- Reason for missing information: No new common duration threshold, such as 12 weeks, was set.
- Required materials and conditions: Administration days, assessment day, and follow-up duration
- Materials to obtain first: Administration days, assessment day, and follow-up duration
- Further research: Compare the timing in the dosing schedule, planned/actual assessment records, and results tables.
- Conditions for verification: Record the difference between actual dates and durations and the level of detail in the retained description.
- Why this condition is needed: Needed to avoid imposing an arbitrary minimum long-term study duration on an acute-symptom question.
- Application exceptions: Do not infer the exact number of days from the description “short-term” alone.
- Remaining uncertainty: No new common duration threshold, such as 12 weeks, was set.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed; M08 Table 8.2.a, M04 §4.6.3; case-specific application
- Related sources: S01, S02

### N07 · How were patients in early pregnancy selected?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The population consists of patients with nausea in early pregnancy, but exact gestational weeks, diagnostic criteria, inpatient status, and inclusion/exclusion are unverified.
- Why unverified: The population dimension has not been removed; the remaining gap is detailed selection information.
- Reason for missing information: The population dimension has not been removed; the remaining gap is detailed selection information.
- Required materials and conditions: Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness
- Materials to obtain first: Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness
- Further research: Obtain selection criteria, baseline tables, diagnostic criteria, and exclusion criteria, and compare them with the original question.
- Conditions for verification: Distinguish what has actually been verified about the population from items that could not be verified.
- Why this condition is needed: Needed to prevent the label “early pregnancy” from standing in for the actual recruitment criteria.
- Application exceptions: Do not extend the population to include hyperemesis gravidarum.
- Remaining uncertainty: The population dimension has not been removed; the remaining gap is detailed selection information.
- Referenced methods: M03 §3.2.1; detailed population conditions are custom-designed
- Related sources: S01, S02

### N08 · Is the definition of the severe-nausea group known?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The Sahakian summary describes improvement especially in the severe-nausea group. The severity threshold, denominator, and overall-group estimate are unverified.
- Why unverified: Benefit for the overall group is not established from the description of the severe group alone.
- Reason for missing information: Benefit for the overall group is not established from the description of the severe group alone.
- Required materials and conditions: Baseline scores, severity threshold, subgroup denominator, and selection criteria
- Materials to obtain first: Baseline scores, severity threshold, subgroup denominator, and selection criteria
- Further research: Compare the subgroup plan, baseline scores, and results tables by arm.
- Conditions for verification: Explain the subgroup definition and actual results, and how they differ from those of the overall group.
- Why this condition is needed: Needed to avoid extending improvement in the severe group to an effect in the overall group.
- Application exceptions: Do not turn unverified baseline severity into a claim that all patients had severe nausea.
- Remaining uncertainty: Benefit for the overall group is not established from the description of the severe group alone.
- Referenced methods: M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom-designed
- Related sources: S01

### N09 · What was the actual placebo?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Recorded as placebo-controlled, but details of composition, common care, and the schedules in both arms are unverified.
- Why unverified: The comparator label and whether actual care was identical are separate matters.
- Reason for missing information: The comparator label and whether actual care was identical are separate matters.
- Required materials and conditions: Placebo composition, appearance, administration schedule, and common care by arm
- Materials to obtain first: Placebo composition, appearance, administration schedule, and common care by arm
- Further research: Link placebo, administration, and common-care documents to the original results.
- Conditions for verification: Separate the retained comparison type from the gap in actual composition details.
- Why this condition is needed: Needed to prevent the label “placebo” from being used as proof that care was identical.
- Application exceptions: Do not infer placebo composition when there is no record.
- Remaining uncertainty: The comparator label and whether actual care was identical are separate matters.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application
- Related sources: S01, S02

### N10 · How much of the actual comparison design is retained?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: S01/S02 are described in the archived summaries as randomized, double-blind, and placebo-controlled. Details on parallel/crossover/cluster design were not obtained.
- Why unverified: This verifies the design record; it does not verify the full original Methods text.
- Reason for missing information: This verifies the design record; it does not verify the full original Methods text.
- Required materials and conditions: Actual parallel/crossover/cluster design, randomization, and blinding
- Materials to obtain first: Actual parallel/crossover/cluster design, randomization, and blinding
- Further research: Compare design information in Methods, allocation plans, and the paper’s results.
- Conditions for verification: Connect the summary-level description of the design that remains with the details that are unverified.
- Why this condition is needed: Because the label RCT alone does not establish that all allocation issues have been resolved.
- Application exceptions: Do not assign crossover/cluster NA solely because the design is unverified.
- Remaining uncertainty: This verifies the design record; it does not verify the full original Methods text.
- Referenced methods: M08 §8.1–8.2.3; case-specific application
- Related sources: S01, S02

### N11 · Have allocation-sequence generation, concealment and baseline balance been verified?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The current summary does not provide details of sequence generation, concealment or baseline balance.
- Why unverified: These are unverified within the retained material; this does not establish non-reporting in the paper or bias.
- Reason for missing information: These are unverified within the retained material; this does not establish non-reporting in the paper or bias.
- Required materials and conditions: Sequence generation, concealment, baseline table and allocation implementation
- Materials to obtain first: Sequence generation, concealment, baseline table and allocation implementation
- Further research: Review allocation and outcome-specific differences using the protocol, Methods and baseline table.
- Conditions for verification: Record the allocation details actually verified and the remaining gaps.
- Why this condition is needed: Needed to avoid certifying the adequacy of allocation on the basis of the word ‘randomized’ alone.
- Application exceptions: No bias is established or additional deduction applied solely on the basis of unverified information.
- Remaining uncertainty: These are unverified within the retained material; this does not establish non-reporting in the paper or bias.
- Referenced methods: M08 §8.1–8.2.3; case-specific application
- Related sources: S01, S02

### N12 · Were prenatal vitamins, rescue medication or concurrent B6 used alongside the intervention?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Concomitant treatment, prenatal vitamins, rescue medication, adherence and arm-specific changes are unverified.
- Why unverified: The unverified status of concurrent B6 was not replaced with additional exposure of 0.
- Reason for missing information: The unverified status of concurrent B6 was not replaced with additional exposure of 0.
- Required materials and conditions: Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm
- Materials to obtain first: Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm
- Further research: Link each arm’s medication, prenatal vitamin, rescue treatment and dosing records to the analysis plan.
- Conditions for verification: Distinguish the effect of interest from gaps in information on actual changes in each arm and how they were handled.
- Why this condition is needed: Needed to avoid mistaking treatment differences for an effect of pyridoxine monotherapy.
- Application exceptions: This does not require every change in both arms to be identical.
- Remaining uncertainty: The unverified status of concurrent B6 was not replaced with additional exposure of 0.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; local application; M08 §8.2.2, M15 §15.3.1; local application
- Related sources: S01, S02

### N13 · Is the nausea score a PUQE total score?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The outcome was recorded as a nausea score, but the scale, range and units are unverified. It was not relabeled as a PUQE total score.
- Why unverified: An unknown scale does not imply an effect of 0.
- Reason for missing information: An unknown scale does not imply an effect of 0.
- Required materials and conditions: Actual scale, range, units, direction and collection method
- Materials to obtain first: Actual scale, range, units, direction and collection method
- Further research: Compare the measurement instrument, items, timepoints and collection procedures with the original results tables.
- Conditions for verification: Separate nausea as the outcome from the unverified identity of the actual measurement instrument.
- Why this condition is needed: Needed to avoid treating different symptom scales as the same outcome.
- Application exceptions: PUQE use has not been verified, so the score is not relabeled as PUQE.
- Remaining uncertainty: An unknown scale does not imply an effect of 0.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M03 §3.2.4; local application
- Related sources: S01, S02

### N14 · Are measurement conditions for assessors and patients the same across arms?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The description as double-blind is retained, but nausea measurement procedures, the assessors’ actual blinding and differences in collection between arms are unverified.
- Why unverified: It was not established that a measurement problem occurred.
- Reason for missing information: It was not established that a measurement problem occurred.
- Required materials and conditions: Outcome collection, blinding in assessment and measurement procedures by arm
- Materials to obtain first: Outcome collection, blinding in assessment and measurement procedures by arm
- Further research: Compare assessment guidance, recording methods and records verifying blinding.
- Conditions for verification: Retain the actual conditions of measurement for the selected nausea outcome and the aspects that cannot be verified.
- Why this condition is needed: Needed to distinguish differences in collecting subjective symptoms from actual differences in effect.
- Application exceptions: The double-blind label and outcome-specific details of blinding are separate.
- Remaining uncertainty: It was not established that a measurement problem occurred.
- Referenced methods: M08 Table 8.2.a, M03 §3.2.4; local application
- Related sources: S01, S02

### N15 · Was nausea a prespecified primary (1st) endpoint?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The selected question concerns nausea scores, but the original trial’s endpoint hierarchy, prespecified timepoints and reasons for changes are unverified.
- Why unverified: Defining the current question does not mean that registration review is complete.
- Reason for missing information: Defining the current question does not mean that registration review is complete.
- Required materials and conditions: Registration, protocol, endpoint/timepoint hierarchy and reasons for changes
- Materials to obtain first: Registration, protocol, endpoint/timepoint hierarchy and reasons for changes
- Further research: Compare the protocol, registration versions and analysis plan with the original results tables.
- Conditions for verification: Distinguish plans that could not be cross-checked from the known nausea findings.
- Why this condition is needed: Needed to avoid retrospectively treating this page’s question as the original trial’s primary (1st) endpoint.
- Application exceptions: Failure to acquire a registration record is not converted into confirmation of non-registration or selective reporting.
- Remaining uncertainty: Defining the current question does not mean that registration review is complete.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M04 §4.6.3; local application
- Related sources: S01, S02

### N16 · Can between-group differences, within-group differences and adjusted effects be distinguished?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The formal overall between-group effect, definitions of baseline/change/end values, analysis population, adjustment and ITT/PP are unverified.
- Why unverified: Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.
- Reason for missing information: Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.
- Required materials and conditions: Analysis population, baseline/end/change values, adjustment and ITT/PP
- Materials to obtain first: Analysis population, baseline/end/change values, adjustment and ITT/PP
- Further research: Link the actual analysis tables, denominators and analysis plan to the selected nausea outcome.
- Conditions for verification: Preserve the distinction between a formal contrast and a qualitative description.
- Why this condition is needed: Needed to avoid converting a description of improvement into a formal placebo-adjusted effect.
- Application exceptions: Do not assume ITT when the analysis is unclear.
- Remaining uncertainty: Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 §8.2.2, M15 §15.3.1; local application
- Related sources: S01, S02

### N17 · Are the overall-group effect size, CI and P value known?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The formal overall-group effect size, CI, P value and dispersion could not be verified from the currently retained summaries.
- Why unverified: This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.
- Reason for missing information: This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.
- Required materials and conditions: Between-group estimate, dispersion, denominator, P value and CI
- Materials to obtain first: Between-group estimate, dispersion, denominator, P value and CI
- Further research: Review the effect, interval, denominator and units in the original Results and analysis tables.
- Conditions for verification: Specify which aspects of the formal overall-group effect cannot be verified.
- Why this condition is needed: Needed to avoid converting an unverified effect into statistical non-significance or no effect.
- Application exceptions: Retain the preserved signal without calculating a new effect.
- Remaining uncertainty: This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M15 §15.3.1–15.3.3; local application
- Related sources: S01, S02

### N18 · What is the figure of 59 people a denominator for?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Sahakian is recorded as having 59 participants. The stage and arm-specific analysis denominators are unverified.
- Why unverified: 59 is a retained number, not a verified arm-specific analysis n.
- Reason for missing information: 59 is a retained number, not a verified arm-specific analysis n.
- Required materials and conditions: Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome
- Materials to obtain first: Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome
- Further research: Obtain CONSORT records, original tables and analysis-population records, and link participant counts at each stage.
- Conditions for verification: Distinguish the verified sample label from the unverified stage/arm-specific denominators.
- Why this condition is needed: Needed to avoid using a sample label as the actual denominator for the nausea analysis.
- Application exceptions: Do not split 59 into arm-specific or event denominators for calculations.
- Remaining uncertainty: 59 is a retained number, not a verified arm-specific analysis n.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed
- Related sources: S01

### N19 · Is the figure of 342 people a denominator for the same regimen?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Vutyavanich is recorded as having 342 participants at 30 mg/day. The participant stage and arm-specific analysis denominators are unverified, and the regimen differs from the main regimen of 25 mg every 8 hours.
- Why unverified: The large sample label was not treated as evidence of precision for the directly assessed regimen.
- Reason for missing information: The large sample label was not treated as evidence of precision for the directly assessed regimen.
- Required materials and conditions: Vutyavanich: participant stages by arm, numbers analyzed and dose
- Materials to obtain first: Vutyavanich: participant stages by arm, numbers analyzed and dose
- Further research: Compare the original supportive-trial results tables with recruitment, allocation, completion and analysis records.
- Conditions for verification: Record the participant counts and the differences in regimens and study families separately.
- Why this condition is needed: Needed to avoid combining the sample at a different dose with the main trial denominator or treating it as independent replication.
- Application exceptions: Do not add 342 and 59 together.
- Remaining uncertainty: The large sample label was not treated as evidence of precision for the directly assessed regimen.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; local application
- Related sources: S02

### N20 · What were the dropouts, missing data and discontinuations, and how were they handled?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The manuscript’s sample records of 59/342 alone cannot establish arm-specific dropout, missing data, discontinuation or handling methods.
- Why unverified: Do not assume 0 missing data or complete follow-up.
- Reason for missing information: Do not assume 0 missing data or complete follow-up.
- Required materials and conditions: Attrition, missing data, reasons and outcome-specific handling by arm
- Materials to obtain first: Attrition, missing data, reasons and outcome-specific handling by arm
- Further research: Compare participant flow, missingness in the original data, reasons for discontinuation and analysis methods.
- Conditions for verification: Separate actual observed losses from the scope of what cannot be verified.
- Why this condition is needed: Needed to avoid treating an unknown analysis denominator as absence of attrition.
- Application exceptions: Do not calculate dropout rates from the retained participant counts alone.
- Remaining uncertainty: Do not assume 0 missing data or complete follow-up.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M08 §8.2.2, M15 §15.3.1; local application
- Related sources: S01, S02

### N21 · Does a trial at a different dose replicate the same regimen?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: TF-SAH-1991 and TF-VUT-1995 were retained separately. The main regimen is 25 mg every 8 hours, and the supportive regimen is 30 mg/day; they are not combined as same-dose replication.
- Why unverified: This verifies the distinction between study families; it does not verify independent funding or use of the same scale.
- Reason for missing information: This verifies the distinction between study families; it does not verify independent funding or use of the same scale.
- Required materials and conditions: Unique study families, ingredient, dose, scale, duration and population
- Materials to obtain first: Unique study families, ingredient, dose, scale, duration and population
- Further research: Compare formulation, population, measurement and analysis across study families to verify the scope of replication.
- Conditions for verification: Explain the actual similarities/differences between the two study families and what remains unverified.
- Why this condition is needed: Needed to avoid upgrading a positive description at a different dose to independent replication of the same regimen.
- Application exceptions: Retain the supportive findings and state the boundaries.
- Remaining uncertainty: This verifies the distinction between study families; it does not verify independent funding or use of the same scale.
- Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application; M04 §4.6.1–4.6.2, M15 §15.3.1; local application
- Related sources: S01, S02

### N22 · Were the vomiting findings the same as those for nausea?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Both the supportive trial’s description of nausea improvement and its less consistent vomiting findings were retained. Vomiting frequency is separate from nausea scores.
- Why unverified: The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.
- Reason for missing information: The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.
- Required materials and conditions: Separate findings, analyses and timepoints for nausea and vomiting
- Materials to obtain first: Separate findings, analyses and timepoints for nausea and vomiting
- Further research: Retain the original nausea and vomiting results tables separately, and compare them with findings for the original question.
- Conditions for verification: Assign positive/inconsistent signals from different findings to their respective endpoints.
- Why this condition is needed: Needed to avoid deleting less consistent vomiting findings or turning them into a nausea effect.
- Application exceptions: Vomiting is not included as a required endpoint for the selected nausea question.
- Remaining uncertainty: The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.
- Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is locally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; local application
- Related sources: S02

### N23 · What degree of reduction is important?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The exact scale, effect interval, and applicable clinically important difference are unverified.
- Why unverified: Retain the qualitative improvement without establishing the magnitude or importance of the benefit.
- Reason for missing information: Retain the qualitative improvement without establishing the magnitude or importance of the benefit.
- Required materials and conditions: Justified scale-specific important differences, between-group CI, and patient interpretation
- Materials to obtain first: Justified scale-specific important differences, between-group CI, and patient interpretation
- Further research: Link scale-validation and patient-importance data to the actual effect interval.
- Conditions for verification: Explain the verified criteria and intervals, or why interpretation is not possible.
- Why this condition is needed: Needed to avoid declaring a definite clinical benefit from an improvement signal alone.
- Application exceptions: Do not create arbitrary score thresholds, minimum participant counts, or minimum numbers of studies.
- Remaining uncertainty: Retain the qualitative improvement without establishing the magnitude or importance of the benefit.
- Referenced methods: M15 §15.3.1–15.3.3; internally applied
- Related sources: S01, S02

### N24 · Have funding, product provision, and conflict-of-interest records for the two trials actually been verified?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Funding, product provision, and COI for the two trials are unverified. The original I1 applies the rule for unverified funding; it does not confirm manufacturer support.
- Why unverified: No new independence assessment or revision of the original axes was performed.
- Reason for missing information: No new independence assessment or revision of the original axes was performed.
- Required materials and conditions: Funding, product provision, author employment, COI, and study families
- Materials to obtain first: Funding, product provision, author employment, COI, and study families
- Further research: Cross-check the papers’ Funding/COI statements, product-supply records, and institutional/study-family records.
- Conditions for verification: Verify funding, product provision, author employment, and COI for each trial by linking them to locations in the actual records. Leave unverified items unverified and distinguish them from the explanation of the original I1 scoring policy.
- Why this condition is needed: Needed to avoid turning the original axis treatment of unverified funding into actual industry support or independent funding.
- Application exceptions: Do not automatically discard results because of interests involved.
- Remaining uncertainty: No new independence assessment or revision of the original axes was performed.
- Referenced methods: Chamgap’s own conditions for independence and attribution. The official methods sections used in this pilot do not validate all these detailed items.
- Related sources: S01, S02

### N25 · Have the actual version, original recommendation text, current status, and links to supporting trials of the ACOG guideline been verified?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: S03 ACOG 2018 is contextual material from an archived summary describing historical recommendations. It was not used as direct effect evidence or a new grading basis.
- Why unverified: The exact current version, full original recommendation text, and status are unverified.
- Reason for missing information: The exact current version, full original recommendation text, and status are unverified.
- Required materials and conditions: Roles, locations, and versions of the guideline, original trials, and archived summaries
- Materials to obtain first: Roles, locations, and versions of the guideline, original trials, and archived summaries
- Further research: If follow-up is authorized, link the guideline’s original text and version, and the trials supporting its recommendations, separately.
- Conditions for verification: Cross-check the guideline’s bibliographic details, version, original recommendations, current status, and links to supporting trials against the locations actually verified. Separate the retained 2018 contextual description from the material not read or cross-checked in this work, and do not use it as direct effect evidence or a new grading basis.
- Why this condition is needed: Needed to avoid treating recommendations as a new effect estimate or grading basis for the selected regimen.
- Application exceptions: The current guideline full text and current status were not read or reviewed in this work.
- Remaining uncertainty: The exact current version, full original recommendation text, and status are unverified.
- Referenced methods: M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internally applied
- Related sources: S03

### N26 · Are the denominators for maternal and fetal adverse events known?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The retained NVP trial summaries alone cannot verify maternal/fetal AE, SAE, discontinuations, or long-term safety.
- Why unverified: The current unverified status does not mean 0 harms or established safety.
- Reason for missing information: The current unverified status does not mean 0 harms or established safety.
- Required materials and conditions: Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm
- Materials to obtain first: Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm
- Further research: Obtain the original trials’ safety tables and arm-level follow-up, exposure, and discontinuation records.
- Conditions for verification: Distinguish the applicability of direct pregnancy-harm records from that of general harm records.
- Why this condition is needed: Needed to avoid treating the existence of efficacy summaries as verification of safety in pregnancy.
- Application exceptions: Do not convert general B6 safety records into fetal event counts for the trials.
- Remaining uncertainty: The current unverified status does not mean 0 harms or established safety.
- Referenced methods: M19 §19.1.2–19.2.4; internally applied; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed
- Related sources: S01, S02, S04, S05

### N27 · What is the scope of applicability of the neuropathy warning?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: General B6 safety records describe neuropathy below 50 mg/day and do not guarantee recovery. These are not arm-level risk rates from NVP trials.
- Why unverified: Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.
- Reason for missing information: Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.
- Required materials and conditions: General neuropathy data, exposure, populations, recovery, and applicability to pregnancy
- Materials to obtain first: General neuropathy data, exposure, populations, recovery, and applicability to pregnancy
- Further research: Review individual exposure, neurological symptoms, recovery follow-up data, and applicability to pregnant populations.
- Conditions for verification: Distinguish the claims in the currently retained official extraction from the gaps in the pregnancy comparison.
- Why this condition is needed: Needed to avoid converting a general warning into a risk rate for short-term pregnancy trials.
- Application exceptions: Retain the harm signal without newly calculating incidence in pregnancy.
- Remaining uncertainty: Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.
- Referenced methods: M19 §19.1.2–19.2.4; internally applied; M03 §3.2.1; detailed population conditions are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed
- Related sources: S04, S05

### N28 · Have the versions, effective dates, and applicability of official upper-limit, warning, and regulatory records been verified?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Retain the EFSA adult chronic total-intake UL of 12 mg/day, the TGA warning above 10 mg/day, and the change for the range above 50 mg/day~200 mg/day scheduled for 2027-06-01 as records at the original cutoff of 2026-09-15.
- Why unverified: Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.
- Reason for missing information: Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.
- Required materials and conditions: Nutritional upper limits, warning thresholds, policy effective dates, and intended uses
- Materials to obtain first: Nutritional upper limits, warning thresholds, policy effective dates, and intended uses
- Further research: During an authorized update, separately verify the actual policy versions, effective dates, and applicability.
- Conditions for verification: Link each official document’s version, publication/effective dates, applicable population, and scope to the locations actually verified. Separate the retained upper limits, warnings, and scheduled changes at the original cutoff from what has not been cross-checked in this work, and distinguish them from treatment doses for pregnancy nausea.
- Why this condition is needed: Needed to avoid turning official policy numbers into recommended treatment doses for pregnancy nausea.
- Application exceptions: Do not describe the regulation scheduled for 2027-06-01 as currently in force.
- Remaining uncertainty: Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.
- Referenced methods: M04 §4.5, §4.6.3; limits on the current material conversion follow the user-defined scope and internal design; M19 §19.1.2–19.2.4; internally applied
- Related sources: S04, S06

### N29 · Is doxylamine-related drowsiness being attributed to B6 alone?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Doxylamine drowsiness information was not transferred to adverse effects of B6 alone. Ginger and prenatal multivitamin results were also kept separate from monotherapy evidence.
- Why unverified: This does not establish that B6 alone has no harms.
- Reason for missing information: This does not establish that B6 alone has no harms.
- Required materials and conditions: Ingredient-specific harms and comparisons for single-ingredient and combination preparations
- Materials to obtain first: Ingredient-specific harms and comparisons for single-ingredient and combination preparations
- Further research: Link the combination’s composition and each ingredient’s safety records to the actual exposure separately.
- Conditions for verification: Explain the preparation/ingredient boundaries and limits on the applicability of the records.
- Why this condition is needed: Needed to avoid attributing another ingredient’s adverse effects to pyridoxine alone.
- Application exceptions: The efficacy and harms of doxylamine combinations are separate.
- Remaining uncertainty: This does not establish that B6 alone has no harms.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M19 §19.1.2–19.2.4; internally applied
- Related sources: S03, S07, S08

### N30 · Are nausea results being used to answer questions about fetal/birth events as well?

Verification status: Not applicable  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The efficacy question in this table concerns nausea severity; it does not also assess hyperemesis gravidarum treatment, hospitalization, or improvement in fetal/birth events.
- Why unverified: Gaps in maternal and fetal safety information remain in the separate harm items.
- Reason for missing information: Gaps in maternal and fetal safety information remain in the separate harm items.
- Required materials and conditions: Separate results for nausea scores and for hospitalization, birth, and fetal clinical events
- Materials to obtain first: Separate results for nausea scores and for hospitalization, birth, and fetal clinical events
- Further research: Review event-specific definitions, denominators, and follow-up separately only when addressing an extension to events.
- Conditions for verification: State the boundary between the selected symptom question and questions about other events.
- Why this condition is needed: Needed to avoid extending symptom reduction to improvement in separate clinical events.
- Application exceptions: Do not impose separate event trials as additional mandatory conditions for the narrow nausea question.
- Remaining uncertainty: Gaps in maternal and fetal safety information remain in the separate harm items.
- Referenced methods: M03 §3.2.4; internally defined boundary for extensions
- Related sources: S01, S02

### N31 · Which of the two doses is better?

Verification status: Not applicable  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The 25 mg every 8 hours and 30 mg/day records belong to different study families and are not combined as direct dose-comparison or optimal-dose evidence.
- Why unverified: A separate dose-related extension was not imposed on the current efficacy conditions.
- Reason for missing information: A separate dose-related extension was not imposed on the current efficacy conditions.
- Required materials and conditions: Direct dose comparisons, exposure, the same scale, and intervals
- Materials to obtain first: Direct dose comparisons, exposure, the same scale, and intervals
- Further research: When adding an optimal-dose question, separately design direct dose comparisons in the same population.
- Conditions for verification: Distinguish the lack of verified direct dose comparisons from the attribution of supportive results.
- Why this condition is needed: Needed to avoid converting summaries from separate trials into a comparison of dose effects.
- Application exceptions: Determining the optimal dose is not an additional requirement for the current narrow question about the main regimen.
- Remaining uncertainty: A separate dose-related extension was not imposed on the current efficacy conditions.
- Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed
- Related sources: S01, S02

### N32 · Does the assessment also address maintenance of effect after discontinuation?

Verification status: Not applicable  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The current short-term nausea comparison does not establish maintenance of effect after discontinuation or prevention of recurrence.
- Why unverified: Gaps in long-term safety were retained separately from direct harms.
- Reason for missing information: Gaps in long-term safety were retained separately from direct harms.
- Required materials and conditions: Separate results for discontinuation, maintenance, and long-term follow-up
- Materials to obtain first: Separate results for discontinuation, maintenance, and long-term follow-up
- Further research: When adding a maintenance question, separately track post-discontinuation assessments, concurrent care, and recurrence.
- Conditions for verification: Record the separate boundary between the selected acute outcome and maintenance of effect.
- Why this condition is needed: Needed to avoid extending short-term symptom results to maintenance or prevention of recurrence.
- Application exceptions: Do not use a minimum long-term follow-up requirement as an arbitrary threshold for the current acute comparison.
- Remaining uncertainty: Gaps in long-term safety were retained separately from direct harms.
- Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed
- Related sources: S01, S02

### N33 · Was effect modification by severe nausea planned in advance?

Verification status: Unverified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The severe-nausea subgroup criteria, prespecification, interactions, and separate CI are unverified.
- Why unverified: Positive subgroup descriptions were not generalized to the whole-group effect.
- Reason for missing information: Positive subgroup descriptions were not generalized to the whole-group effect.
- Required materials and conditions: Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals
- Materials to obtain first: Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals
- Further research: Cross-check the protocol and analysis plan against severity-specific results/interactions.
- Conditions for verification: Distinguish the levels of verification for prespecified definitions and formal interactions.
- Why this condition is needed: Needed to avoid using subgroup improvement as the main effect for all patients.
- Application exceptions: Retain the subgroup description and its exploratory/planned status.
- Remaining uncertainty: Positive subgroup descriptions were not generalized to the whole-group effect.
- Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internally applied; M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed
- Related sources: S01

### N34 · Were C46 and the original axes automatically carried over to the new table?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The original C·46 and B/P/R1/I1/EX/B1/CX, with no_human_study=false, were preserved. The original explanation of the signal, unverified effect size, unverified funding and sample limitation of 59 was also retained.
- Why unverified: The grade is not used as a condition status, an individual probability of success or a safety assessment.
- Reason for missing information: The grade is not used as a condition status, an individual probability of success or a safety assessment.
- Required materials and conditions: Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions
- Materials to obtain first: Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions
- Further research: When a separately authorized change arises, review it while preserving the original judgment, materials, condition version and affected fields.
- Conditions for verification: Preserve the original C46, axes and limitations exactly, without creating new judgment values.
- Why this condition is needed: Needed to avoid turning citation of the original assessment into a new efficacy score or condition-fulfillment rate.
- Application exceptions: The original B1, I1, EX, and CX reflect historical policy, not new calculations in this table.
- Remaining uncertainty: The grade is not used as a condition status, an individual probability of success or a safety assessment.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed
- Related sources: S01, S02

### N35 · Do 8 bibliographic records represent 8 clinical trials?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: S01/S02 are two trial families with different regimens. S03 is retained as guideline context, and S04–08 as general official safety/nutrition and drug information; they are not counted as 8 trials.
- Why unverified: No independent-participant total or total number of human studies was calculated.
- Reason for missing information: No independent-participant total or total number of human studies was calculated.
- Required materials and conditions: Links among reports, the two trial families, the guideline and official safety information
- Materials to obtain first: Links among reports, the two trial families, the guideline and official safety information
- Further research: Link report/trial/result identities and leave unknown relationships unknown.
- Conditions for verification: Record each report’s material type, family, endpoint and limitations concerning overlap.
- Why this condition is needed: This is needed to avoid turning a bibliographic count into a count of independent pregnancy trials.
- Application exceptions: Do not assume independence and pool included trials/participants.
- Remaining uncertainty: No independent-participant total or total number of human studies was calculated.
- Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application; M04 §4.6.1–4.6.2, M15 §15.3.1; local application
- Related sources: S01, S02, S03, S04, S05, S06, S07, S08

### N36 · Have actual acquisition, reading and original bytes of the archived summaries and linked original materials been verified?

Verification status: Partly verified  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The currently retained archived-summary text, bibliographic information and linked summaries were actually read. provided_secondary_summary and provided_official_source_extraction are historical material-type records in the manuscript; external full texts have not been read in this task.
- Why unverified: Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.
- Reason for missing information: Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.
- Required materials and conditions: Current archived-summary locations/values/SHA, original-material types, historical access and current access actions
- Materials to obtain first: Current archived-summary locations/values/SHA, original-material types, historical access and current access actions
- Further research: When subsequent acquisition is authorized, record the actual file/location/date/SHA as a new access event.
- Conditions for verification: For each material, record the exact location, value and SHA of the currently retained archived summary and its actual reading, together with the verified scope of acquisition, reading and file SHA for the linked original material. Do not inherit a historical material-type declaration as current source-file acquisition or full-text reading; leave unverified aspects unresolved.
- Why this condition is needed: This is needed to avoid turning a link or a historical access level into a full-text reading in this task.
- Application exceptions: External originals/separate legacy and safety-extraction source files/ZIPs were not opened in this task.
- Remaining uncertainty: Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.
- Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink specification are internally designed
- Related sources: S01, S02, S03, S04, S05, S06, S07, S08

### N37 · Is this the latest conclusion from the entire current literature?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: The evidence reference date of 2026-09-15 was preserved. This conversion was limited to the currently archived summaries, without a new clinical search or rechecking guidelines/registrations/corrections/retractions.
- Why unverified: Statements about the presence or absence of materials are limited to this preserved scope.
- Reason for missing information: Statements about the presence or absence of materials are limited to this preserved scope.
- Required materials and conditions: Evidence reference date, actual review date and scope of searches/corrections/retractions
- Materials to obtain first: Evidence reference date, actual review date and scope of searches/corrections/retractions
- Further research: During an authorized update, add the actual search queries, original materials and verification of publication status as new events.
- Conditions for verification: Record the reference point of the retained materials separately from the time of review for the current conversion.
- Why this condition is needed: This is needed to avoid turning the absence of a new search into 0 studies or confirmation of current recommendations.
- Application exceptions: The original review date of 2026-09-15 is not an access date for this task.
- Remaining uncertainty: Statements about the presence or absence of materials are limited to this preserved scope.
- Referenced methods: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and internal design
- Related sources: S01, S02, S03

### N38 · Which items should change when which materials are acquired?

Verification status: Met  
Reading scope: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review

- Current findings: Record from the preservation-table review dated 2026-10-05: The original revision_triggers for result recovery, preparation/population corrections, plans/denominators, maternal/fetal safety, retractions/errors and guidelines/actual effective dates were linked to the corresponding gaps.
- Why unverified: No subsequent research was performed, and no new score/judgment was created and applied.
- Reason for missing information: No subsequent research was performed, and no new score/judgment was created and applied.
- Required materials and conditions: Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections
- Materials to obtain first: Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections
- Further research: When separately authorized, preserve the complete original text before the change and record additions of materials, revisions of conditions and changes to the judgment separately.
- Conditions for verification: Keep the original update triggers, linked conditions/materials and preservation of historical original text distinct.
- Why this condition is needed: This is needed to avoid treating the addition of a material as automatic confirmation of an effect or revision of the condition version.
- Application exceptions: Do not modify the original judgment, related manuscripts or the site while preparing this table.
- Remaining uncertainty: No subsequent research was performed, and no new score/judgment was created and applied.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink specification are internally designed; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and internal design
- Related sources: S01, S02, S03, S04, S05, S06, S07, S08

## Evidence and sources

### S01

Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study

[Source](https://pubmed.ncbi.nlm.nih.gov/2047064/)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: 59 participants; 25 mg every 8 hours; improvement described especially in severe nausea; formal overall-group effect/CI/per-arm analysis n unverified.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| PubMed original-trial index/abstract entry point | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. |

### S02

Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial

[Source](https://pubmed.ncbi.nlm.nih.gov/7573262/)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: 342 participants; 30 mg/day; nausea improvement/less consistent vomiting findings; not same-dose replication; formal effect/CI/per-arm analysis n unverified.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| PubMed original-trial index/abstract entry point | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. |

### S03

ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy

[Source](https://doi.org/10.1097/AOG.0000000000002456)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: Context describing historical recommendations. Not a formal direct pyridoxine effect or evidence for a new grade.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Recommendations described in the historical record; current full text and current status not checked. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| Guideline DOI entry point | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Recommendations described in the historical record; current full text and current status not checked. This record does not mean that the external original material was acquired or its full text read in this task. |

### S04

TGA 2026. Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)

[Source](https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: Neuropathy/policy record. Distinguish the >10 warning and the >50~200 change scheduled for 2027-06-01, which was future at the original reference date. Not a risk rate in pregnancy.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| Entry point for the official TGA safety/regulatory document | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. This record does not mean that the external original material was acquired or its full text read in this task. |

### S05

TGA 2026. Are you unknowingly taking too much vitamin B6?

[Source](https://www.tga.gov.au/news/blog/are-you-unknowingly-taking-too-much-vitamin-b6)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: Records of neuropathy below 50 mg/day, cumulative intake and recovery not guaranteed. Denominators/causal risks in pregnancy trials are unverified.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| Entry point for the official TGA safety document | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. This record does not mean that the external original material was acquired or its full text read in this task. |

### S06

EFSA 2023. Scientific opinion on the tolerable upper intake level for vitamin B6

[Source](https://www.efsa.europa.eu/en/efsajournal/pub/8006)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: The adult chronic total-intake UL of 12 mg/day is not a treatment dose for pregnancy nausea.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Abstract; Conclusions, adult UL derivation. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| Entry point for the original official EFSA opinion | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Abstract; Conclusions, adult UL derivation. This record does not mean that the external original material was acquired or its full text read in this task. |

### S07

NIH ODS. Vitamin B6: Fact Sheet for Health Professionals

[Source](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: General context on forms, nutritional intake and harms of excess. Not a monotherapy efficacy comparison result in pregnancy.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| Entry point for official NIH ODS information | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. This record does not mean that the external original material was acquired or its full text read in this task. |

### S08

MedlinePlus. Pyridoxine drug information

[Source](https://medlineplus.gov/druginfo/meds/a682587.html)

Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.  
Findings recorded in the summary: Retained context on special precautions and side effects; original revised 2017-08-15, current lookups 0. Research amounts are not converted into personal doses.  
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.  
Independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Retained archived-summary bibliographic information and linked summaries/historical records | Retained locally | Acquired | Summary read | Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Special precautions; side effects; revised 15 August 2017. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text. |
| MedlinePlus drug-information entry point | Unverified (0 current external lookups) | Access not attempted | Not read | Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Special precautions; side effects; revised 15 August 2017. This record does not mean that the external original material was acquired or its full text read in this task. |

## Review criteria and methods

These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score.

- M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations of the intervention. · Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool
- M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because a result was not reported. · Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool
- M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement and selective reporting. · Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool
- M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool
- M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence. · Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool

## What the statuses mean

- Partly verified: Some content in the currently archived summaries has been verified; specific gaps in effects, preparations, denominators and original materials remain
- Unverified: Required items could not be verified within the preserved scope; this does not mean 0 studies, no effect or safety
- Review incomplete: Comparison with original materials/searches have not been performed within the permitted scope
- Not reported: A status limited to the absence of the item from the specific material/section that was read
- Inaccessible: Used only for materials for which access was actually attempted and failed. Not assigned to clinical materials in this task
- Insufficient evidence matching the conditions: Used only when, after reviewing relevant studies within a defined scope, the evidence is insufficient to answer the condition. Not applied across the entire body of evidence in this task
- Not applicable: For the selected acute-nausea question, separate events, optimal-dose or maintenance extensions are not imposed as additional requirements
- Conflicting records: When materials that are difficult to reconcile have been compared for the same question, timepoint and analysis. Not assigned merely because numbers differ between reviews
- Met: Verification of the specified question, attribution and preservation/linking; not certification of direct efficacy, pregnancy safety or full-text reading

## Change history

2026-11-01 · Public page/materials 1.0. The public view and materials were prepared from the existing 38 items. No new clinical search, change in verification status or scoring was performed.