Autism linked to epilepsy drug use in pregnancy

Children born to mothers who take valproate during pregnancy are at increased risk for developing autism compared with children of women who did not take the epilepsy drug, Danish research shows.

The study involved data on 655,615 children born to 428,407 mothers between 1996 and 2006, including 508 children exposed to valproate during pregnancy. Over follow-up to a mean age of 8.8 years, 5437 children were diagnosed with autism spectrum disorder, including 2067 with childhood autism.

Among children exposed to valproate, the risk for autism spectrum disorder was 2.9-fold greater, and the risk for childhood autism was 5.1-fold greater than among unexposed children (absolute 14-year risk: 4.4 vs 1.5%; 2.5 vs 0.5%, respectively).

The risks for autism spectrum disorder and childhood autism were also 2.2-fold, and 5.6-fold greater, respectively, in exposed children than in children of mothers who stopped taking valproate at least 30 days before conception.

Writing in JAMA, the study authors stress that it is important to carefully balance these concerns against the benefits of valproate in epilepsy control.

"Because autism spectrum disorders are serious conditions with life-long implications for affected children and their families, even a moderate increase in risk may have major health importance," say Jakob Christensen (Aarhus University Hospital) and colleagues.

"Still, the absolute risk of autism spectrum disorder was less than 5%, which is important to take into account when counseling women about the use of valproate in pregnancy."

However, in an accompanying editorial, Kimford Meador and David Loring (both from Emory University, Atlanta, Georgia, USA) say that current rates of valproate prescriptions among girls and women of reproductive age indicate that the risks of fetal exposure are not sufficiently taken into account.

"This raises concern as to whether these women are receiving adequate information for informed consent based on a full understanding of the treatment risks and alternative therapies," they write.

Alternative medications should be used wherever possible, and women should be informed of the risks associated with valproate even if they are not currently planning to conceive, they conclude.

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