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. 2018 Jan;32(1):100-111.
doi: 10.1111/ppe.12414. Epub 2017 Oct 6.

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring

Ramkripa Raghavan  1 , Anne W Riley  1 , Heather Volk  2 , Deanna Caruso  1 , Lynn Hironaka  3 , Laura Sices  3 , Xiumei Hong  1 , Guoying Wang  1 , Yuelong Ji  1 , Martha Brucato  4 , Anastacia Wahl  3 , Tom Stivers  3 , Colleen Pearson  3 , Barry Zuckerman  3 , Elizabeth A Stuart  2   5 , Rebecca Landa  6 , M Daniele Fallin  2 , Xiaobin Wang  1   7
Affiliations

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring

Ramkripa Raghavan et al. Paediatr Perinat Epidemiol. 2018 Jan.

Abstract

Background: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 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 B12 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 B12 (≥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 B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.

Keywords: Autism; folate; prenatal supplement intake; vitamin B12.

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Conflict of interest statement

Conflict of interest: None of the authors have a conflict of interest pertaining to this work

Figures

Figure 1
Figure 1. Maternal self-reported multivitamin supplement intake and ASD risk in offspring in the Boston Birth Cohort (N=1,257)
Adjusted association between maternal multivitamin supplement intake during 1st, 2nd and 3rd trimesters and risk of ASD in offspring (Ref category: supplement intake 3-5 times/week); Adjusted for maternal characteristics: age, education, parity, BMI, smoking status, diabetes status, race and MTHFR genotype; offspring characteristics: gestational age, sex and year of birth
Figure 2
Figure 2. Association between maternal folate and vitamin B12 concentrations and risk of ASD in offspring in the Boston Birth Cohort (N=1,257)
Unadjusted association between maternal plasma folate (panel A) and plasma vitamin B12 (panel B) levels at different cut-off points and risk of ASD in offspring. The unadjusted HR for plasma folate (panel A) was truncated at 65 nmol/L due to the small sample size beyond the specified cutoff point (unadjusted HR for mothers whose plasma folate ≥65 nmol/L was 1.9, 95% CI 1.0, 3.4; n=113). The unadjusted HR for plasma vitamin B12 (panel B) was truncated at 700 pmol/L due to declining sample sizes beyond the specified cutoff point (unadjusted HR for mothers whose plasma vitamin B12 ≥700 pmol/L was 2.8, 95% CI, 1.3, 6.0; n=45).
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