Maternal Multivitamin Intake, Plasma Folate and Vitamin B 12 Levels and Autism Spectrum Disorder Risk in Offspring
Open accessAbstract
Background: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B 12 levels at birth and child's Autism Spectrum Disorder ( ASD ) risk. Methods: This report included 1257 mother–child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B 12 were measured from samples taken 2–3 days after birth. Results: Moderate (3–5 times/week) self‐reported supplementation during pregnancy was associated with decreased risk of ASD , consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD . Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval ( CI ) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B 12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). Conclusion: There was a ‘U shaped’ relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B 12 levels at birth were associated with ASD risk. This hypothesis‐generating study does not question the importance of consuming adequate folic acid and vitamin B 12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B 12 exposure in‐utero on early brain development.
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Recent concerns have been raised regarding a potential association between very high plasma levels of maternal folate and risk of autism spectrum disorders.
“However, recent concerns have been raised regarding a potential association between very high plasma levels of maternal folate and risk of autism spectrum disorders.533”
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- Authors
- Raghavan, R., Riley, A. W., Volk, H., Caruso, D., Hironaka, L., Sices, L., Hong, X., Wang, G., Ji, Y., Brucato, M., Wahl, A., Stivers, T., Pearson, C., Zuckerman, B., Stuart, E. A., Landa, R., Fallin, M. D., & Wang, X.
- Affiliations
- Johns Hopkins University (US)
- Boston University (US)
- Kennedy Krieger Institute (US)
- Corresponding author
- Fallin, M. Daniele
- Wang, Xiaobin
- ORCID
- Venue
- Paediatric and Perinatal Epidemiology
- Publisher
- Wiley
- Published
- 2017-10-06
- Volume
- 32
- Issue
- 1
- Pages
- 100-111
- ISSN
- 0269-5022 (ISSN-L)
- 1365-3016
- PMC
- PMC5796848
- OpenAlex
- W2761662546
- Cited by
- 233
- References
- 58
- Citations by year
- 2026: 14 · 2025: 29 · 2024: 32 · 2023: 21 · 2022: 26 · 2021: 32 · 2020: 34 · 2019: 26 · 2018: 14 · 2017: 3 · 2016: 1
- FWCI
- 18.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Paediatric and Perinatal Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Maternal and Child Health Bureau (R40MC27443)
- March of Dimes Foundation (20‐FY02‐56, #21‐FY07‐605)
- National Institutes of Health (R21ES011666, R01HD041702, R21HD066471, U01AI090727, R21AI079872, R01HD086013)
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- autism spectrum disorder, pregnancy, prenatal exposure, U-shaped relationship, MTHFR genotype, early brain development, offspring risk
- MeSH terms
- Autism Spectrum Disorder, Adult, Child, Female, Folic Acid, Humans, Interviews as Topic, Male, Pregnancy, Prospective Studies, Risk Factors, Vitamin B 12, Vitamins, Biomarkers, Dietary Supplements
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