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Cited by 233Folate and B Vitamins ResearchAutism Spectrum Disorder ResearchPharmacological Effects and Toxicity Studies

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Maternal Multivitamin Intake, Plasma Folate and Vitamin B 12 Levels and Autism Spectrum Disorder Risk in Offspring

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Raghavan, Ramkripa, Riley, Anne W., Volk, Heather, Caruso, Deanna, Hironaka, Lynn, Sices, Laura, Hong, Xiumei, Wang, Guoying, Ji, Yuelong, Brucato, Martha, Wahl, Anastacia, Stivers, Tom, Pearson, Colleen, Zuckerman, Barry, Stuart, Elizabeth A., Landa, Rebecca, Fallin, M. Daniele, Wang, Xiaobin·2018·Paediatric and Perinatal Epidemiology
DOI 10.1111/ppe.12414PMC PMC5796848
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Abstract

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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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
DOI
10.1111/ppe.12414
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
FWCI
18.40
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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 › Nursing › Nutrition and Dietetics › 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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