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

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Distinct claimWhich nausea comparison is addressed?Required (selected comparison for nausea in early pregnancy)	A single main claim of reduced nausea severity in early pregnancy was selected. The original claim_count=1, and there is no subclaims key. S01 S02	Confirming the identity of the question and demonstrating efficacy are separate matters.	Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity	Compare the population, intervention, and endpoint boundaries in the manuscript and trial results separately.
2	Met	Full text not readStored summary read	N02 · Related assessmentsIs this the same question as 127·3095?Required (selected comparison for nausea in early pregnancy)	The current related_records distinguishes 127 as the historical PMS+pregnancy nausea composite and 3095 as a separate PMS-only claim. S01 S03	This is a reading of relationship metadata, not a review of the full related manuscripts.	Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim	If follow-up is authorized, compare the exact questions in the related authoritative versions to check for duplication.
3	Partly verified	Full text not readStored summary read	N03 · Molecule and saltHave the actual substance and salt been verified?Required (selected comparison for nausea in early pregnancy)	Recorded as oral pyridoxine monotherapy, but hydrochloride identity is unverified. It is not automatically equivalent to pyridoxal or PLP. S01 S07	Verification of the exact salt remains outstanding.	Pyridoxine and the exact salt, active ingredient, and route	Link composition and quality documents to the results for the relevant trial arm.
4	Unverified	Full text not readStored summary read	N04 · Product specificationsAre the manufacturing origin, manufacturer, and dosage form known?Required (selected comparison for nausea in early pregnancy)	Manufacturing origin, manufacturer, purity, batch, tablet/capsule, release type, and excipients are unverified within the retained materials. S01 S02	This does not mean that the information is absent from the original paper as a whole.	Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients	Compare batch and formulation documents with administration records to verify actual exposure.
5	Partly verified	Full text not readStored summary read	N05 · Dose and frequencyAre 25 mg every 8 hours and actual total exposure the same?Required (selected comparison for nausea in early pregnancy)	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. S01	Do not use 75 as the actual amount taken or a personally recommended dose.	Nominal dose, interval, actual intake, concurrent B6, and adherence	Obtain administration, medication-taking, and concurrent supplementation records by arm to verify total exposure.
6	Unverified	Full text not readStored summary read	N06 · Duration and timingAre the number of treatment days and the outcome assessment day known?Required (selected comparison for nausea in early pregnancy)	The retained description refers to a short-term trial, but the exact treatment days, assessment day, and follow-up duration are unverified. S01 S02	No new common duration threshold, such as 12 weeks, was set.	Administration days, assessment day, and follow-up duration	Compare the timing in the dosing schedule, planned/actual assessment records, and results tables.
7	Unverified	Full text not readStored summary read	N07 · Population selectionHow were patients in early pregnancy selected?Required (selected comparison for nausea in early pregnancy)	The population consists of patients with nausea in early pregnancy, but exact gestational weeks, diagnostic criteria, inpatient status, and inclusion/exclusion are unverified. S01 S02	The population dimension has not been removed; the remaining gap is detailed selection information.	Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness	Obtain selection criteria, baseline tables, diagnostic criteria, and exclusion criteria, and compare them with the original question.
8	Partly verified	Full text not readStored summary read	N08 · Baseline severityIs the definition of the severe-nausea group known?Required (selected comparison for nausea in early pregnancy)	The Sahakian summary describes improvement especially in the severe-nausea group. The severity threshold, denominator, and overall-group estimate are unverified. S01	Benefit for the overall group is not established from the description of the severe group alone.	Baseline scores, severity threshold, subgroup denominator, and selection criteria	Compare the subgroup plan, baseline scores, and results tables by arm.
9	Partly verified	Full text not readStored summary read	N09 · Comparator compositionWhat was the actual placebo?Required (selected comparison for nausea in early pregnancy)	Recorded as placebo-controlled, but details of composition, common care, and the schedules in both arms are unverified. S01 S02	The comparator label and whether actual care was identical are separate matters.	Placebo composition, appearance, administration schedule, and common care by arm	Link placebo, administration, and common-care documents to the original results.
10	Partly verified	Full text not readStored summary read	N10 · DesignHow much of the actual comparison design is retained?Required (selected comparison for nausea in early pregnancy)	S01/S02 are described in the archived summaries as randomized, double-blind, and placebo-controlled. Details on parallel/crossover/cluster design were not obtained. S01 S02	This verifies the design record; it does not verify the full original Methods text.	Actual parallel/crossover/cluster design, randomization, and blinding	Compare design information in Methods, allocation plans, and the paper’s results.
11	Unverified	Full text not readStored summary read	N11 · Allocation and baseline balanceHave allocation-sequence generation, concealment and baseline balance been verified?Required (selected comparison for nausea in early pregnancy)	The current summary does not provide details of sequence generation, concealment or baseline balance. S01 S02	These are unverified within the retained material; this does not establish non-reporting in the paper or bias.	Sequence generation, concealment, baseline table and allocation implementation	Review allocation and outcome-specific differences using the protocol, Methods and baseline table.
12	Unverified	Full text not readStored summary read	N12 · Adherence and rescue treatmentWere prenatal vitamins, rescue medication or concurrent B6 used alongside the intervention?Required (selected comparison for nausea in early pregnancy)	Concomitant treatment, prenatal vitamins, rescue medication, adherence and arm-specific changes are unverified. S01 S02	The unverified status of concurrent B6 was not replaced with additional exposure of 0.	Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm	Link each arm’s medication, prenatal vitamin, rescue treatment and dosing records to the analysis plan.
13	Partly verified	Full text not readStored summary read	N13 · Measurement scaleIs the nausea score a PUQE total score?Required (selected comparison for nausea in early pregnancy)	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. S01 S02	An unknown scale does not imply an effect of 0.	Actual scale, range, units, direction and collection method	Compare the measurement instrument, items, timepoints and collection procedures with the original results tables.
14	Unverified	Full text not readStored summary read	N14 · Blinding in measurementAre measurement conditions for assessors and patients the same across arms?Required (selected comparison for nausea in early pregnancy)	The description as double-blind is retained, but nausea measurement procedures, the assessors’ actual blinding and differences in collection between arms are unverified. S01 S02	It was not established that a measurement problem occurred.	Outcome collection, blinding in assessment and measurement procedures by arm	Compare assessment guidance, recording methods and records verifying blinding.
15	Unverified	Full text not readStored summary read	N15 · Endpoint hierarchyWas nausea a prespecified primary (1st) endpoint?Required (selected comparison for nausea in early pregnancy)	The selected question concerns nausea scores, but the original trial’s endpoint hierarchy, prespecified timepoints and reasons for changes are unverified. S01 S02	Defining the current question does not mean that registration review is complete.	Registration, protocol, endpoint/timepoint hierarchy and reasons for changes	Compare the protocol, registration versions and analysis plan with the original results tables.
16	Unverified	Full text not readStored summary read	N16 · Effect definitionCan between-group differences, within-group differences and adjusted effects be distinguished?Required (selected comparison for nausea in early pregnancy)	The formal overall between-group effect, definitions of baseline/change/end values, analysis population, adjustment and ITT/PP are unverified. S01 S02	Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.	Analysis population, baseline/end/change values, adjustment and ITT/PP	Link the actual analysis tables, denominators and analysis plan to the selected nausea outcome.
17	Unverified	Full text not readStored summary read	N17 · Effect and intervalAre the overall-group effect size, CI and P value known?Required (selected comparison for nausea in early pregnancy)	The formal overall-group effect size, CI, P value and dispersion could not be verified from the currently retained summaries. S01 S02	This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.	Between-group estimate, dispersion, denominator, P value and CI	Review the effect, interval, denominator and units in the original Results and analysis tables.
18	Partly verified	Full text not readStored summary read	N18 · Main trial denominatorWhat is the figure of 59 people a denominator for?Required (selected comparison for nausea in early pregnancy)	Sahakian is recorded as having 59 participants. The stage and arm-specific analysis denominators are unverified. S01	59 is a retained number, not a verified arm-specific analysis n.	Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome	Obtain CONSORT records, original tables and analysis-population records, and link participant counts at each stage.
19	Partly verified	Full text not readStored summary read	N19 · Supportive trial denominatorIs the figure of 342 people a denominator for the same regimen?Required (selected comparison for nausea in early pregnancy)	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. S02	The large sample label was not treated as evidence of precision for the directly assessed regimen.	Vutyavanich: participant stages by arm, numbers analyzed and dose	Compare the original supportive-trial results tables with recruitment, allocation, completion and analysis records.
20	Unverified	Full text not readStored summary read	N20 · Missing data and attritionWhat were the dropouts, missing data and discontinuations, and how were they handled?Required (selected comparison for nausea in early pregnancy)	The manuscript’s sample records of 59/342 alone cannot establish arm-specific dropout, missing data, discontinuation or handling methods. S01 S02	Do not assume 0 missing data or complete follow-up.	Attrition, missing data, reasons and outcome-specific handling by arm	Compare participant flow, missingness in the original data, reasons for discontinuation and analysis methods.
21	Met	Full text not readStored summary read	N21 · Replication and dose differencesDoes a trial at a different dose replicate the same regimen?Required (selected comparison for nausea in early pregnancy)	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. S01 S02	This verifies the distinction between study families; it does not verify independent funding or use of the same scale.	Unique study families, ingredient, dose, scale, duration and population	Compare formulation, population, measurement and analysis across study families to verify the scope of replication.
22	Met	Full text not readStored summary read	N22 · Contrary and other findingsWere the vomiting findings the same as those for nausea?Required (selected comparison for nausea in early pregnancy)	Both the supportive trial’s description of nausea improvement and its less consistent vomiting findings were retained. Vomiting frequency is separate from nausea scores. S02	The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.	Separate findings, analyses and timepoints for nausea and vomiting	Retain the original nausea and vomiting results tables separately, and compare them with findings for the original question.
23	Unverified	Full text not readStored summary read	N23 · Clinical importanceWhat degree of reduction is important?Required (selected comparison for nausea in early pregnancy)	The exact scale, effect interval, and applicable clinically important difference are unverified. S01 S02	Retain the qualitative improvement without establishing the magnitude or importance of the benefit.	Justified scale-specific important differences, between-group CI, and patient interpretation	Link scale-validation and patient-importance data to the actual effect interval.
24	Unverified	Full text not readStored summary read	N24 · Funding and independenceHave funding, product provision, and conflict-of-interest records for the two trials actually been verified?Required (selected comparison for nausea in early pregnancy)	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. S01 S02	No new independence assessment or revision of the original axes was performed.	Funding, product provision, author employment, COI, and study families	Cross-check the papers’ Funding/COI statements, product-supply records, and institutional/study-family records.
25	Partly verified	Full text not readStored summary read	N25 · Material types and guidelinesHave the actual version, original recommendation text, current status, and links to supporting trials of the ACOG guideline been verified?Supplementary; essential for guideline interpretation	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. S03	The exact current version, full original recommendation text, and status are unverified.	Roles, locations, and versions of the guideline, original trials, and archived summaries	If follow-up is authorized, link the guideline’s original text and version, and the trials supporting its recommendations, separately.
26	Unverified	Full text not readStored summary read	N26 · Direct harmsAre the denominators for maternal and fetal adverse events known?Required (selected comparison for nausea in early pregnancy)	The retained NVP trial summaries alone cannot verify maternal/fetal AE, SAE, discontinuations, or long-term safety. S01 S02 S04 S05	The current unverified status does not mean 0 harms or established safety.	Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm	Obtain the original trials’ safety tables and arm-level follow-up, exposure, and discontinuation records.
27	Partly verified	Full text not readStored summary read	N27 · General B6 harmsWhat is the scope of applicability of the neuropathy warning?Required (selected comparison for nausea in early pregnancy)	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. S04 S05	Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.	General neuropathy data, exposure, populations, recovery, and applicability to pregnancy	Review individual exposure, neurological symptoms, recovery follow-up data, and applicability to pregnant populations.
28	Partly verified	Full text not readStored summary read	N28 · Regulation and upper limitsHave the versions, effective dates, and applicability of official upper-limit, warning, and regulatory records been verified?Supplementary; essential for policy and safety interpretation	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. S04 S06	Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.	Nutritional upper limits, warning thresholds, policy effective dates, and intended uses	During an authorized update, separately verify the actual policy versions, effective dates, and applicability.
29	Met	Full text not readStored summary read	N29 · Separating harms by preparationIs doxylamine-related drowsiness being attributed to B6 alone?Required (selected comparison for nausea in early pregnancy)	Doxylamine drowsiness information was not transferred to adverse effects of B6 alone. Ginger and prenatal multivitamin results were also kept separate from monotherapy evidence. S03 S07 S08	This does not establish that B6 alone has no harms.	Ingredient-specific harms and comparisons for single-ingredient and combination preparations	Link the combination’s composition and each ingredient’s safety records to the actual exposure separately.
30	Not applicable	Full text not readStored summary read	N30 · Symptoms and eventsAre nausea results being used to answer questions about fetal/birth events as well?Supplementary (essential only when extending to separate events)	The efficacy question in this table concerns nausea severity; it does not also assess hyperemesis gravidarum treatment, hospitalization, or improvement in fetal/birth events. S01 S02	Gaps in maternal and fetal safety information remain in the separate harm items.	Separate results for nausea scores and for hospitalization, birth, and fetal clinical events	Review event-specific definitions, denominators, and follow-up separately only when addressing an extension to events.
31	Not applicable	Full text not readStored summary read	N31 · Optimal doseWhich of the two doses is better?Supplementary (essential only when extending to the optimal dose)	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. S01 S02	A separate dose-related extension was not imposed on the current efficacy conditions.	Direct dose comparisons, exposure, the same scale, and intervals	When adding an optimal-dose question, separately design direct dose comparisons in the same population.
32	Not applicable	Full text not readStored summary read	N32 · Persistence and recoveryDoes the assessment also address maintenance of effect after discontinuation?Supplementary (essential only when extending to maintenance of effect)	The current short-term nausea comparison does not establish maintenance of effect after discontinuation or prevention of recurrence. S01 S02	Gaps in long-term safety were retained separately from direct harms.	Separate results for discontinuation, maintenance, and long-term follow-up	When adding a maintenance question, separately track post-discontinuation assessments, concurrent care, and recurrence.
33	Unverified	Full text not readStored summary read	N33 · Subgroup planningWas effect modification by severe nausea planned in advance?Required (selected comparison for nausea in early pregnancy)	The severe-nausea subgroup criteria, prespecification, interactions, and separate CI are unverified. S01	Positive subgroup descriptions were not generalized to the whole-group effect.	Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals	Cross-check the protocol and analysis plan against severity-specific results/interactions.
34	Met	Full text not readStored summary read	N34 · Preserving original valuesWere C46 and the original axes automatically carried over to the new table?Required (selected comparison for nausea in early pregnancy)	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. S01 S02	The grade is not used as a condition status, an individual probability of success or a safety assessment.	Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions	When a separately authorized change arises, review it while preserving the original judgment, materials, condition version and affected fields.
35	Met	Full text not readStored summary read	N35 · Reports/familiesDo 8 bibliographic records represent 8 clinical trials?Required (selected comparison for nausea in early pregnancy)	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. S01 S02 S03 S04 S05 S06 S07 S08	No independent-participant total or total number of human studies was calculated.	Links among reports, the two trial families, the guideline and official safety information	Link report/trial/result identities and leave unknown relationships unknown.
36	Partly verified	Full text not readStored summary read	N36 · Current readingHave actual acquisition, reading and original bytes of the archived summaries and linked original materials been verified?Required (selected comparison for nausea in early pregnancy)	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. S01 S02 S03 S04 S05 S06 S07 S08	Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.	Current archived-summary locations/values/SHA, original-material types, historical access and current access actions	When subsequent acquisition is authorized, record the actual file/location/date/SHA as a new access event.
37	Met	Full text not readStored summary read	N37 · Search/reference dateIs this the latest conclusion from the entire current literature?Required (selected comparison for nausea in early pregnancy)	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. S01 S02 S03	Statements about the presence or absence of materials are limited to this preserved scope.	Evidence reference date, actual review date and scope of searches/corrections/retractions	During an authorized update, add the actual search queries, original materials and verification of publication status as new events.
38	Met	Full text not readStored summary read	N38 · Update conditionsWhich items should change when which materials are acquired?Required (selected comparison for nausea in early pregnancy)	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. S01 S02 S03 S04 S05 S06 S07 S08	No subsequent research was performed, and no new score/judgment was created and applied.	Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections	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.

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38 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Archived Korean and English manuscripts and case-specific condition and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date on which the archived materials were checked, not the date of a search for the latest clinical literature.
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.

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S01 · Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study

Source

Material type: Retained secondary (2nd) summary of the main dose-matched trial
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained secondary (2nd) summary of the supportive trial at a different dose
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained secondary (2nd) summary providing guideline context
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained record of an extraction of general official safety information
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained record of an extraction of general official safety information
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained record of an extraction on the official nutritional upper intake limit
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained record of an extraction of official nutrition/general safety information
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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

Material type: Retained record of an extraction of official drug information
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 stored 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.
Study overlap and independent replication: Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0

Public availability, access and reading status by material
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.

Report counts versus independent study counts

The 8 source records do not mean 8 independent clinical trials. The main regimen and the supportive regimen at a different dose belong to separate trial families; the guideline and general safety, nutrition and drug information are not counted as pregnancy-nausea trials. S01: TF-SAH-1991: Main evidence, archived-summary level / S02: TF-VUT-1995: Supportive evidence, not independent same-dose replication / S03, S04, S05, S06, S07, S08: Guideline context/general safety and nutrition/drug information. Not counted as independent pregnancy-nausea trials.

Review criteria

Version NGM-v3096-ORAL-PYRIDOXINE-EARLY-PREGNANCY-NAUSEA-1.1 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which nausea comparison is addressed?

Required materials and conditions: Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity
Conditions for verification: Link the exact original wording of the effect claim to the inclusion and exclusion boundaries.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Vomiting, PUQE totals, hyperemesis gravidarum, PMS, and combination products are separate.
Why this condition is needed: Needed to keep different pregnancy-related effects from being combined into a single efficacy claim.
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

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

Required materials and conditions: Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim
Conditions for verification: Preserve the distinctions recorded in the current relationship object and the limitation that the underlying texts were not read.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: The related manuscripts and ZIP archives were not newly opened in this review.
Why this condition is needed: Needed to keep related record numbers from being combined as the same study or the same efficacy claim.
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

N03 · Have the actual substance and salt been verified?

Required materials and conditions: Pyridoxine and the exact salt, active ingredient, and route
Conditions for verification: Record verified pyridoxine identity separately from the unverified salt.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not assume whether it is hydrochloride.
Why this condition is needed: Needed to prevent findings for PLP or combination products from being repurposed under the name vitamin B6.
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

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

Required materials and conditions: Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients
Conditions for verification: Identify separately only the items verified in the directly studied preparation.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not assign the composition of a doxylamine product to the preparation being directly assessed.
Why this condition is needed: Needed to prevent the single-ingredient dosage form in the question from being mistaken for actual product specifications.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed

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

Required materials and conditions: Nominal dose, interval, actual intake, concurrent B6, and adherence
Conditions for verification: Preserve the nominal regimen, historical arithmetic, and actual total exposure separately.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: 75 mg/day quotes the schedule arithmetic in the manuscript; it is not newly calculated.
Why this condition is needed: Needed to prevent schedule arithmetic from being treated as actual intake or a 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

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

Required materials and conditions: Administration days, assessment day, and follow-up duration
Conditions for verification: Record the difference between actual dates and durations and the level of detail in the retained description.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not infer the exact number of days from the description “short-term” alone.
Why this condition is needed: Needed to avoid imposing an arbitrary minimum long-term study duration on an acute-symptom question.
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

N07 · How were patients in early pregnancy selected?

Required materials and conditions: Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness
Conditions for verification: Distinguish what has actually been verified about the population from items that could not be verified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not extend the population to include hyperemesis gravidarum.
Why this condition is needed: Needed to prevent the label “early pregnancy” from standing in for the actual recruitment criteria.
Referenced methods: M03 §3.2.1; detailed population conditions are custom-designed

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

Required materials and conditions: Baseline scores, severity threshold, subgroup denominator, and selection criteria
Conditions for verification: Explain the subgroup definition and actual results, and how they differ from those of the overall group.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not turn unverified baseline severity into a claim that all patients had severe nausea.
Why this condition is needed: Needed to avoid extending improvement in the severe group to an effect in the overall group.
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

N09 · What was the actual placebo?

Required materials and conditions: Placebo composition, appearance, administration schedule, and common care by arm
Conditions for verification: Separate the retained comparison type from the gap in actual composition details.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not infer placebo composition when there is no record.
Why this condition is needed: Needed to prevent the label “placebo” from being used as proof that care was identical.
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

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

Required materials and conditions: Actual parallel/crossover/cluster design, randomization, and blinding
Conditions for verification: Connect the summary-level description of the design that remains with the details that are unverified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not assign crossover/cluster NA solely because the design is unverified.
Why this condition is needed: Because the label RCT alone does not establish that all allocation issues have been resolved.
Referenced methods: M08 §8.1–8.2.3; case-specific application

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

Required materials and conditions: Sequence generation, concealment, baseline table and allocation implementation
Conditions for verification: Record the allocation details actually verified and the remaining gaps.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: No bias is established or additional deduction applied solely on the basis of unverified information.
Why this condition is needed: Needed to avoid certifying the adequacy of allocation on the basis of the word ‘randomized’ alone.
Referenced methods: M08 §8.1–8.2.3; case-specific application

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

Required materials and conditions: Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm
Conditions for verification: Distinguish the effect of interest from gaps in information on actual changes in each arm and how they were handled.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: This does not require every change in both arms to be identical.
Why this condition is needed: Needed to avoid mistaking treatment differences for an effect of pyridoxine monotherapy.
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

N13 · Is the nausea score a PUQE total score?

Required materials and conditions: Actual scale, range, units, direction and collection method
Conditions for verification: Separate nausea as the outcome from the unverified identity of the actual measurement instrument.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: PUQE use has not been verified, so the score is not relabeled as PUQE.
Why this condition is needed: Needed to avoid treating different symptom scales as the same outcome.
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

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

Required materials and conditions: Outcome collection, blinding in assessment and measurement procedures by arm
Conditions for verification: Retain the actual conditions of measurement for the selected nausea outcome and the aspects that cannot be verified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: The double-blind label and outcome-specific details of blinding are separate.
Why this condition is needed: Needed to distinguish differences in collecting subjective symptoms from actual differences in effect.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; local application

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

Required materials and conditions: Registration, protocol, endpoint/timepoint hierarchy and reasons for changes
Conditions for verification: Distinguish plans that could not be cross-checked from the known nausea findings.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Failure to acquire a registration record is not converted into confirmation of non-registration or selective reporting.
Why this condition is needed: Needed to avoid retrospectively treating this page’s question as the original trial’s primary (1st) endpoint.
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

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

Required materials and conditions: Analysis population, baseline/end/change values, adjustment and ITT/PP
Conditions for verification: Preserve the distinction between a formal contrast and a qualitative description.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not assume ITT when the analysis is unclear.
Why this condition is needed: Needed to avoid converting a description of improvement into a formal placebo-adjusted 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

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

Required materials and conditions: Between-group estimate, dispersion, denominator, P value and CI
Conditions for verification: Specify which aspects of the formal overall-group effect cannot be verified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Retain the preserved signal without calculating a new effect.
Why this condition is needed: Needed to avoid converting an unverified effect into statistical non-significance or no effect.
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

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

Required materials and conditions: Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome
Conditions for verification: Distinguish the verified sample label from the unverified stage/arm-specific denominators.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not split 59 into arm-specific or event denominators for calculations.
Why this condition is needed: Needed to avoid using a sample label as the actual denominator for the nausea analysis.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed

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

Required materials and conditions: Vutyavanich: participant stages by arm, numbers analyzed and dose
Conditions for verification: Record the participant counts and the differences in regimens and study families separately.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not add 342 and 59 together.
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.
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

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

Required materials and conditions: Attrition, missing data, reasons and outcome-specific handling by arm
Conditions for verification: Separate actual observed losses from the scope of what cannot be verified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not calculate dropout rates from the retained participant counts alone.
Why this condition is needed: Needed to avoid treating an unknown analysis denominator as absence of attrition.
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

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

Required materials and conditions: Unique study families, ingredient, dose, scale, duration and population
Conditions for verification: Explain the actual similarities/differences between the two study families and what remains unverified.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Retain the supportive findings and state the boundaries.
Why this condition is needed: Needed to avoid upgrading a positive description at a different dose to independent replication of the same regimen.
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

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

Required materials and conditions: Separate findings, analyses and timepoints for nausea and vomiting
Conditions for verification: Assign positive/inconsistent signals from different findings to their respective endpoints.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Vomiting is not included as a required endpoint for the selected nausea question.
Why this condition is needed: Needed to avoid deleting less consistent vomiting findings or turning them into a nausea effect.
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

N23 · What degree of reduction is important?

Required materials and conditions: Justified scale-specific important differences, between-group CI, and patient interpretation
Conditions for verification: Explain the verified criteria and intervals, or why interpretation is not possible.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not create arbitrary score thresholds, minimum participant counts, or minimum numbers of studies.
Why this condition is needed: Needed to avoid declaring a definite clinical benefit from an improvement signal alone.
Referenced methods: M15 §15.3.1–15.3.3; internally applied

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

Required materials and conditions: Funding, product provision, author employment, COI, and study families
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.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not automatically discard results because of interests involved.
Why this condition is needed: Needed to avoid turning the original axis treatment of unverified funding into actual industry support or independent funding.
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.

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

Required materials and conditions: Roles, locations, and versions of the guideline, original trials, and archived summaries
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.
Requirement and applicability: Supplementary; essential for guideline interpretation
Application exceptions: The current guideline full text and current status were not read or reviewed in this work.
Why this condition is needed: Needed to avoid treating recommendations as a new effect estimate or grading basis for the selected regimen.
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

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

Required materials and conditions: Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm
Conditions for verification: Distinguish the applicability of direct pregnancy-harm records from that of general harm records.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not convert general B6 safety records into fetal event counts for the trials.
Why this condition is needed: Needed to avoid treating the existence of efficacy summaries as verification of safety in pregnancy.
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

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

Required materials and conditions: General neuropathy data, exposure, populations, recovery, and applicability to pregnancy
Conditions for verification: Distinguish the claims in the currently retained official extraction from the gaps in the pregnancy comparison.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Retain the harm signal without newly calculating incidence in pregnancy.
Why this condition is needed: Needed to avoid converting a general warning into a risk rate for short-term pregnancy trials.
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

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

Required materials and conditions: Nutritional upper limits, warning thresholds, policy effective dates, and intended uses
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.
Requirement and applicability: Supplementary; essential for policy and safety interpretation
Application exceptions: Do not describe the regulation scheduled for 2027-06-01 as currently in force.
Why this condition is needed: Needed to avoid turning official policy numbers into recommended treatment doses for pregnancy nausea.
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

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

Required materials and conditions: Ingredient-specific harms and comparisons for single-ingredient and combination preparations
Conditions for verification: Explain the preparation/ingredient boundaries and limits on the applicability of the records.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: The efficacy and harms of doxylamine combinations are separate.
Why this condition is needed: Needed to avoid attributing another ingredient’s adverse effects to pyridoxine alone.
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

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

Required materials and conditions: Separate results for nausea scores and for hospitalization, birth, and fetal clinical events
Conditions for verification: State the boundary between the selected symptom question and questions about other events.
Requirement and applicability: Supplementary (essential only when extending to separate events)
Application exceptions: Do not impose separate event trials as additional mandatory conditions for the narrow nausea question.
Why this condition is needed: Needed to avoid extending symptom reduction to improvement in separate clinical events.
Referenced methods: M03 §3.2.4; internally defined boundary for extensions

N31 · Which of the two doses is better?

Required materials and conditions: Direct dose comparisons, exposure, the same scale, and intervals
Conditions for verification: Distinguish the lack of verified direct dose comparisons from the attribution of supportive results.
Requirement and applicability: Supplementary (essential only when extending to the optimal dose)
Application exceptions: Determining the optimal dose is not an additional requirement for the current narrow question about the main regimen.
Why this condition is needed: Needed to avoid converting summaries from separate trials into a comparison of dose effects.
Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed

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

Required materials and conditions: Separate results for discontinuation, maintenance, and long-term follow-up
Conditions for verification: Record the separate boundary between the selected acute outcome and maintenance of effect.
Requirement and applicability: Supplementary (essential only when extending to maintenance of effect)
Application exceptions: Do not use a minimum long-term follow-up requirement as an arbitrary threshold for the current acute comparison.
Why this condition is needed: Needed to avoid extending short-term symptom results to maintenance or prevention of recurrence.
Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed

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

Required materials and conditions: Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals
Conditions for verification: Distinguish the levels of verification for prespecified definitions and formal interactions.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Retain the subgroup description and its exploratory/planned status.
Why this condition is needed: Needed to avoid using subgroup improvement as the main effect for all patients.
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

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

Required materials and conditions: Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions
Conditions for verification: Preserve the original C46, axes and limitations exactly, without creating new judgment values.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: The original B1, I1, EX, and CX reflect historical policy, not new calculations in this table.
Why this condition is needed: Needed to avoid turning citation of the original assessment into a new efficacy score or condition-fulfillment rate.
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

N35 · Do 8 bibliographic records represent 8 clinical trials?

Required materials and conditions: Links among reports, the two trial families, the guideline and official safety information
Conditions for verification: Record each report’s material type, family, endpoint and limitations concerning overlap.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not assume independence and pool included trials/participants.
Why this condition is needed: This is needed to avoid turning a bibliographic count into a count of independent pregnancy trials.
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

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

Required materials and conditions: Current archived-summary locations/values/SHA, original-material types, historical access and current access actions
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.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: External originals/separate legacy and safety-extraction source files/ZIPs were not opened in this task.
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.
Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink specification are internally designed

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

Required materials and conditions: Evidence reference date, actual review date and scope of searches/corrections/retractions
Conditions for verification: Record the reference point of the retained materials separately from the time of review for the current conversion.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: The original review date of 2026-09-15 is not an access date for this task.
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.
Referenced methods: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and internal design

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

Required materials and conditions: Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections
Conditions for verification: Keep the original update triggers, linked conditions/materials and preservation of historical original text distinct.
Requirement and applicability: Required (selected comparison for nausea in early pregnancy)
Application exceptions: Do not modify the original judgment, related manuscripts or the site while preparing this table.
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.
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

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations of the intervention.
Extent of review: 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

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Distinguish studies from reports and link them; do not omit a study solely because a result was not reported.
Extent of review: 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

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement and selective reporting.
Extent of review: 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

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.
Extent of review: 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

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.
Extent of review: 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/material version 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.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-15) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Which nausea comparison is addressed?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Confirming the identity of the question and demonstrating efficacy are separate matters.
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.
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?

Current findings: The current related_records distinguishes 127 as the historical PMS+pregnancy nausea composite and 3095 as a separate PMS-only claim.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This is a reading of relationship metadata, not a review of the full related manuscripts.
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.
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?

Current findings: Recorded as oral pyridoxine monotherapy, but hydrochloride identity is unverified. It is not automatically equivalent to pyridoxal or PLP.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Verification of the exact salt remains outstanding.
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.
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?

Current findings: Manufacturing origin, manufacturer, purity, batch, tablet/capsule, release type, and excipients are unverified within the retained materials.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This does not mean that the information is absent from the original paper as a whole.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Do not use 75 as the actual amount taken or a personally recommended dose.
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.
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?

Current findings: The retained description refers to a short-term trial, but the exact treatment days, assessment day, and follow-up duration are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: No new common duration threshold, such as 12 weeks, was set.
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.
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?

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.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The population dimension has not been removed; the remaining gap is detailed selection information.
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.
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?

Current findings: The Sahakian summary describes improvement especially in the severe-nausea group. The severity threshold, denominator, and overall-group estimate are unverified.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Benefit for the overall group is not established from the description of the severe group alone.
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.
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?

Current findings: Recorded as placebo-controlled, but details of composition, common care, and the schedules in both arms are unverified.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The comparator label and whether actual care was identical are separate matters.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This verifies the design record; it does not verify the full original Methods text.
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.
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?

Current findings: The current summary does not provide details of sequence generation, concealment or baseline balance.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: These are unverified within the retained material; this does not establish non-reporting in the paper or bias.
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.
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?

Current findings: Concomitant treatment, prenatal vitamins, rescue medication, adherence and arm-specific changes are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The unverified status of concurrent B6 was not replaced with additional exposure of 0.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: An unknown scale does not imply an effect of 0.
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.
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?

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.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: It was not established that a measurement problem occurred.
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.
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?

Current findings: The selected question concerns nausea scores, but the original trial’s endpoint hierarchy, prespecified timepoints and reasons for changes are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Defining the current question does not mean that registration review is complete.
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.
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?

Current findings: The formal overall between-group effect, definitions of baseline/change/end values, analysis population, adjustment and ITT/PP are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.
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.
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?

Current findings: The formal overall-group effect size, CI, P value and dispersion could not be verified from the currently retained summaries.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.
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.
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?

Current findings: Sahakian is recorded as having 59 participants. The stage and arm-specific analysis denominators are unverified.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: 59 is a retained number, not a verified arm-specific analysis n.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The large sample label was not treated as evidence of precision for the directly assessed regimen.
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.
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?

Current findings: The manuscript’s sample records of 59/342 alone cannot establish arm-specific dropout, missing data, discontinuation or handling methods.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Do not assume 0 missing data or complete follow-up.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This verifies the distinction between study families; it does not verify independent funding or use of the same scale.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.
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.
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?

Current findings: The exact scale, effect interval, and applicable clinically important difference are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Retain the qualitative improvement without establishing the magnitude or importance of the benefit.
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.
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?

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.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: No new independence assessment or revision of the original axes was performed.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The exact current version, full original recommendation text, and status are unverified.
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.
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?

Current findings: The retained NVP trial summaries alone cannot verify maternal/fetal AE, SAE, discontinuations, or long-term safety.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The current unverified status does not mean 0 harms or established safety.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: This does not establish that B6 alone has no harms.
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.
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?

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.
Verification status: Not applicable
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Gaps in maternal and fetal safety information remain in the separate harm items.
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.
Referenced methods: M03 §3.2.4; internally defined boundary for extensions

Related sources S01 S02

N31 · Which of the two doses is better?

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.
Verification status: Not applicable
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: A separate dose-related extension was not imposed on the current efficacy conditions.
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.
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?

Current findings: The current short-term nausea comparison does not establish maintenance of effect after discontinuation or prevention of recurrence.
Verification status: Not applicable
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Gaps in long-term safety were retained separately from direct harms.
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.
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?

Current findings: The severe-nausea subgroup criteria, prespecification, interactions, and separate CI are unverified.
Verification status: Unverified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Positive subgroup descriptions were not generalized to the whole-group effect.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: The grade is not used as a condition status, an individual probability of success or a safety assessment.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: No independent-participant total or total number of human studies was calculated.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: Statements about the presence or absence of materials are limited to this preserved scope.
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.
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?

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.
Verification status: Met
Materials actually read: The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review
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.
Remaining uncertainty: No subsequent research was performed, and no new score/judgment was created and applied.
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.
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

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