Taking folic acid and/or multivitamin supplements preceding and during pregnancy is associated with a lower risk of offspring developing autism spectrum disorder (ASD), an observational epidemiologic study published Jan. 3 showed.

The findings could have important public health implications, reported Stephen Z. Levine, PhD, and his associates.

The case-cohort study included 45,300 Israeli children who were born between January 2003 and December 2007; the study followed them up until Jan. 26, 2015. The investigators classified the children into three categories depending on their mothers’ supplement regimen: folic acid (vitamin B9), multivitamin supplement, or some combination of the two. Furthermore, Dr. Levine and his associates looked at each category in either of two time intervals: “before pregnancy (540-271 days before childbirth) and during pregnancy (270 days before childbirth up to the date of childbirth).”

The investigators found that 572 children, or 1.3%, received an ASD diagnosis. Dr. Levine and his associates found that children whose mothers took folic acid and multivitamin supplements during pregnancy had a lower risk of developing ASD (relative risk, 0.27; 95% confidence interval, 0.22-0.33; P less than .001), compared with those whose mothers took no supplements. Similarly, there was reduced risk among those whose mothers took only folic acid during pregnancy (RR, 0.32; CI, 0.26-0.41; P less than .001) or only multivitamins (RR, 0.35; CI, 0.28-0.44; P less than .001). Likewise, lower risks were seen among offspring whose mothers took supplements before pregnancy: Compared with no supplements, the RR was 0.39 for folic acid and/or multivitamins (CI, 0.30-0.50; P less than .001), 0.56 for just folic acid (95%CI, 0.42-0.74; P = .001), and 0.36 for just multivitamins (95%CI, 0.24-0.52; P less than .001). Similar associations were found among male and female offspring.

The associations did not hold, however, among parents who had a psychiatric condition. “This finding may reflect noncompliance, higher rates of vitamin deficiency, or poor diet among persons with psychiatric conditions,” wrote Dr. Levine , of the department of community mental health at the University of Haifa, Israel, and his associates in JAMA Psychiatry .

Another important finding is that maternal exposure to folic acid and multivitamin supplements 2 years before pregnancy is tied to a lower ASD risk.

The investigators acknowledged that the study was limited by their inability to determine possible confounding factors, such as the vehicle of vitamin dispensations, use of over-the-counter supplements, false-positive classifications from noncompliance, and absence of information on gestational age. In addition, they said, “causality cannot be inferred from observational studies such as this one.” In light of those limitations, investigators said, additional studies replicating these findings are needed.

The study was funded by several entities, including the National Institutes of Health, the Fredrik and Ingrid Thuring Foundation, and the Swedish Society of Medicine. Dr. Levine reported receiving support from Shire Pharmaceuticals, and coauthor Arad Kodesh, MD, is an employee of Meuhedet Health Services. No other relevant financial disclosures were reported.


SOURCE: Levine SZ et al. JAMA Psychiatry. 2018 Jan 3. doi: 10.1001/jamapsychiatry.2017.4050 .