Maternal Folic Acid, Multivitamin Exposure Reduces Autism Risk

Folic acid (FA) and multivitamin supplementation prior to and during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) in offspring compared with children born from women who were not exposed to FA and multivitamin supplementation, according to findings from a case-control cohort study published in JAMA Psychiatry.¹

“There is a risk reduction in taking folic acid and multivitamin in this study,” according to Thomas Frazier, PhD, chief science officer, Autism Speaks, “which is consistent with other studies showing similar findings.”

According to Frazier, the findings from this research will hopefully increase the use of FA and multivitamin supplementation among women of child-bearing age.

“There are already recommendations for women to take folic acid for the prevention of neural tube defects,” added Frazier, “and other conditions related to that. I’m unsure if we’ll see a major change in clinical practice with this, but there is hope.”

Some of the research focused on folic acid and ASD have been led by researchers at Autism Speaks, an organization spearheading scientific research in the field of management, and treatment of patients with ASD.

“One of the studies we’ve funded is on folinic acid,” commented Frazier, “a close variant of folic acid.”

This study demonstrated that folinic acid was associated with improved communication in autism,² findings which provide researchers “some hope that if this is replicated it might be a useful supplement approach for improved communication in ASD patients.”

A total of 45,300 Israeli offspring born between 2003—2007 who were evaluated from birth up to January 26, 2015, were included in this analysis (22,090 girls and 23,210 boys; mean [SD] age, 10.0 [1.4] years at follow-up).

To determine the risk for ASD, investigators compared offspring born to mothers who supplemented with FA and multivitamins before and during pregnancy versus offspring born to mothers who were not exposed to supplementation.

Approximately 1.3% (n = 572) of the children included in this study had an ASD diagnosis at follow-up. Offspring of mothers who supplemented with FA and/or multivitamins prior to pregnancy had a significantly lower risk for ASD compared with offspring of mothers who were not exposed to a supplementation regimen (RR, 0.39; 95% CI, 0.30-0.50; P <.001).

Additionally, exposure to FA and/or multivitamins during pregnancy was associated with a reduced likelihood of having offspring with an ASD diagnosis at follow-up (RR, 0.27; 95% CI, 0.22-0.33; P <.001).

In sensitivity analyses, similar significant associations were found between a lower ASD risk and pre-pregnancy FA supplementation only (RR, 0.56; 95% CI, 0.42-0.74; P =.001), FA supplementation only during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P <.001), multivitamins only prior to pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P <.001), and maternal exposure to multivitamins during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P <.001).

A potential limitation to this study was the researchers’ inability to perform a sibling control analysis due to the limited sample size. In addition, the observational design of this study precludes the ability to conclude causality factors associated with the findings.

REFERENCE

1. Levine SZ, Kodesh A, Viktorin A, et al. Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring [published online January 3, 2018]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2017.4050.
2. Frye RE, Slattery J, Delhey L, et al. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial [published online October 18, 2016]. Mol Psychiatry. doi: 10.1038/mp.2016.168.

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