Tier 4 — mechanistic

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring

Gary M Shaw, Suzan L Carmichael, Wei Yang, Steve Selvin, Donna M Schaffer
American journal of epidemiology 2004 160(2):102-109

Bibliography

PubMed
PMID 15234930
DOI
10.1093/aje/kwh187
Funding
Indexed grant support: U50/CCU913241 — ODCDC CDC HHS — United States. The indexed list may not contain the complete funding declaration.
Competing interests
A competing-interest declaration was not available in the indexed record or accessible disclosure metadata.

Study snapshot

DesignCase-control study
ModelHuman participants
Sample424 neural-tube-defect cases and 440 controls
InterventionHabitual dietary choline and/or betaine intake; no randomized TMG treatment
DurationPericonceptional diet recalled after pregnancy
EndpointsNeural-tube defects; Maternal diet

What the study showed, in plain terms

Published in 2004, this source examined human observational and biomarker research. Design: Case-control study. Sample/model: 424 neural-tube-defect cases and 440 controls. The exposure or intervention was Habitual dietary choline and/or betaine intake; no randomized TMG treatment. Follow-up or treatment period: Periconceptional diet recalled after pregnancy.

The lowest odds occurred with a dietary pattern high in choline, betaine and methionine, rather than an isolated betaine intervention.

Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.

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Key findings

  • The lowest odds occurred with a dietary pattern high in choline, betaine and methionine, rather than an isolated betaine intervention.
  • The recorded outcome domains were Neural-tube defects; Maternal diet.
  • The exposure was observed rather than assigned as an isolated supplement treatment.

What this study can and cannot tell us

  • Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.
  • Confounding, dietary patterns, illness, medication use and reverse causation can influence an association. Blood or dietary concentrations do not identify the effect of starting a capsule.
  • Source basis: Indexed abstract and bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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Elham Sharifi-Zahabi et al. · Journal of diabetes research · 2026
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Association of choline and betaine with the risk of cardiovascular disease and all-cause mortality: Meta-analysis
Qinglin Yang et al. · European journal of clinical investigation · 2023
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Association of choline and betaine levels with cancer incidence and survival: A meta-analysis
Jiyoung Youn et al. · Clinical nutrition (Edinburgh, Scotland) · 2019

Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology