Vitamins in Early Pregnancy and Autism Risk

Autism was less likely to recur in high-risk families when mothers took prenatal vitamins — particularly folic acid and perhaps iron as well — in the first month of their pregnancy, an analysis of MARBLES study data found.

Of 241 children with older siblings who had autism spectrum disorder (ASD), those whose mothers took prenatal vitamins during the first month were half as likely to receive an ASD diagnosis compared to those whose mothers did not, after adjusting for maternal education (adjusted relative risk 0.50, 95% CI 0.30-0.81), reported Rebecca Schmidt, PhD, of the University of California, Davis, and colleagues.

Children whose mothers took prenatal vitamins in early pregnancy also had significantly lower severity scores on the Autism Diagnostic Observation Schedule (ADOS) compared to children whose mothers did not (adjusted estimated difference –0.60, 95% CI –0.97 to –0.23), the researchers wrote in JAMA Psychiatry.

“Younger siblings are at a higher risk and because they also share a lot of genetics and familial factors, it was interesting for us to [determine] whether this environmental exposure like supplementation would influence the risk as much as it did for the general population” Schmidt told MedPage Today.

Daniele Fallin, PhD, of John Hopkins Bloomberg School of Public Health and the Wendy Klag Center for Autism and Developmental Disabilities in Baltimore, commented that the results are “consistent” with many prior reports indicating that supplementation prior to conception or in the early stages of pregnancy can protect against autism, similar to folic acid’s prevention of neural tube defects.

But there could also be risks with very high levels of supplementation, particularly at the end of pregnancy, she added, though this requires further examination.

“What this builds towards is the idea that supplementation for women of childbearing ages could be important because most of the evidence is prior to the pregnancy,” said Fallin, who was not involved with the research. “This study didn’t really address over-supplementation and didn’t look at whether extremely high levels are also a risk factor.”

Current CDC guidelines recommend women of childbearing age take 400 mcg of folic acid per day and women with prior pregnancies involving neural tube defects consume 4,000 mcg of folic acid each day, one month before becoming pregnant, and through the first 3 months of pregnancy. These recommendations are aimed at preventing neural tube defects, but some studies have suggested that folic acid may protect against autism to some degree.

In this study, researchers recruited mothers who previously had a child with confirmed ASD and were pregnant or planning to become pregnant from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) study. Supplement intake information was measured for the 6 months before pregnancy and then each month throughout pregnancy via phone interviews. Children were assessed at 6 months through age 3.

Of the 241 children included in this analysis (58.1% male), about half (52.3%) of children had typical development, 22.8% met ASD criteria, and 24.9% were classified as having non-typical development, defined by low scores on the Mullen Scales of Early Learning scale, elevated ADOS scores, or both.

Compared to mothers who did not take prenatal vitamins in the first month of pregnancy, those who did were more educated (59.4% vs 38.9% ), more likely to have private health insurance (85.8% vs 67.6%), and more likely to have had an intentional pregnancy (78.9% vs 44.2%), the authors reported.

Nearly all mothers (95.9%) reported consuming prenatal vitamins during pregnancy, but just 36.1% reported taking them in the 6 months before pregnancy, they noted.

Overall, 14.1% of children whose mothers taking prenatal vitamins in the first month of pregnancy were diagnosed with ASD compared to 32.7% of children of mothers who were not, Schmidt and colleagues reported. The association between ASD and prenatal vitamin use did not significantly differ when researchers adjusted for race or ethnicity or maternal age. However, females did have a lower ASD risk compared to males, they noted.

Schmidt and colleagues detected a “modest” dose trend for mean daily folic acid supplementation, with mothers in the highest tertile of folic acid intake demonstrating the greatest reduction in ASD risk, and women taking ≥600 mcg being significantly less likely to have children with ASD. The same pattern was not observed for multivitamins, which typically contain <400 mcg, the authors reported.

This “implies that the association between prenatal vitamin use and ASD in high-risk siblings could, at least partly, be attributed to the high folic acid content in prenatal vitamins, as has been previously observed in general population studies, but other nutrients like iron could also be playing a role,” they added.

Iron intake from supplements was also associated with reduced autism risk, but Schmidt and colleagues explained that it was unclear whether this was independent from the apparent protective effect of f0lic acid, since doses of the two typically correlate in multivitamins.

The authors noted that the study is limited by its small sample size and the possibility of residual confounding, such as whether prenatal vitamin use is linked with increased “health-conscious” behaviors. Also, the current analysis did not examine other components of multivitamins besides folic acid and iron.