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Maternal Folic Acid and Multivitamin Supplementation and Risk of Autism Spectrum Disorders Among an Israeli Birth Cohort
The role of maternal folic acid and multivitamin supplement use before and during pregnancy and the risk of Autism Spectrum Disorders (ASD) in offspring is unclear.
Objectives:
To examine the associations between maternal folic acid and multivitamin supplement use before and during pregnancy and the risk of ASD in offspring.
Methods:
Design: A case-cohort of 45,300 Israeli children born 2003 – 2007, followed-up from birth to January 26th, 2015 for the risk of ASD. The cases comprised of all children diagnosed with ASD by an Israeli health provider and controls comprised of a random sample of 33% of all live born children in Israel 2003 to 2007.
Exposures: Maternal vitamin supplements were classified for folic acid (B9), multivitamin supplements (ATC A11 vitamins: A, B C and D), and any combination thereof, exposed in the intervals before and during pregnancy.
Main outcome(s) and Measure(s): The association between maternal vitamin supplementation and the risk of ASD in the children was quantified with relative risks (RR) and their 95% confidence intervals (CI) fitting Cox regression models and adjusting for year of birth, parental psychiatric history, Socioeconomic status, maternal and paternal age and parity. Extensive sensitivity analyses were performed to test the robustness of the results.
Results:
Maternal folic acid and/or multivitamin supplement exposure before pregnancy was statistically significantly (P<.01) associated with a lower likelihood of ASD in the offspring compared to no exposure before pregnancy, RR=0.39 (95% CI: 0.30-0.50). Maternal folic acid and/or multivitamin supplement exposure during pregnancy was statistically significantly (P<.01) associated with a lower likelihood of ASD in offspring compared to no exposure during pregnancy, RR=0.27 (95% CI: 0.22-0.33). Corresponding RR’s was estimated; for maternal folic acid before pregnancy at RR=0.56 (95% CI: 0.42-0.74); during pregnancy at RR=0.32 (95% CI: 0.26-0.41) and for multivitamin supplements before pregnancy at RR=0.36 (95% CI: 0.24-0.52) and during pregnancy at RR=0.35 (95% CI: 0.28-0.44). The results remained statistically significant across sensitivity analyses.
Conclusions: Maternal intake of folic acid and multivitamin supplements before, and during pregnancy are associated with a reduced risk of ASD in the offspring, compared to offspring of mothers without such intake.