Epilepsy Drug Increases Risk of Autism

A study including more than half a million Danish children finds that children born to mothers who took the antiepileptic drug valproate during pregnancy were much more likely to develop autism.

Children whose mothers used the epilepsy drug valproate during pregnancy had a significantly increased risk for developing autism spectrum disorders and childhood autism, according to the results of a study published in the April 24, 2013, edition of the Journal of the American Medical Association.

Previous studies have associated antiepileptic drugs such as valproate with an increased risk of congenital malformations and delayed cognitive development in children when taken during pregnancy. However, researchers still do not know much about these drugs and the risk of other serious neuropsychiatric disorders.

The researchers conducted a population-based study of children born in Denmark from 1996 to 2006 and used national registers to identify children exposed to valproate during pregnancy and those diagnosed with different forms of autism, including childhood autism, Asperger syndrome, atypical autism, and other unspecified developmental disorders. The children were followed from birth until December 31, 2010, unless they were diagnosed with autism, emigrated, or died first. The data were adjusted to account for a number of factors, including parents’ age at conception, family psychiatric history, and child’s sex.

Of the 655,615 children included in the study, 5437 were diagnosed with autism spectrum disorder, including 2067 with childhood autism. More than 2500 children in the study were exposed to antiepileptic drugs during pregnancy, and 508 were exposed to valproate. The researchers found a 4.42% risk of autism spectrum disorders for children exposed to valproate compared with a 1.53% risk for children not exposed to the drug. For childhood autism, the risk for children exposed to valproate was 2.5% compared with 0.48% for children not exposed.

Despite the increased risk of autism associated with taking valproate during pregnancy, the authors suggest that potential mothers with epilepsy should carefully weigh the benefits of the drug for epilepsy control against the possible negative effects it may have on their children.

"Because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance,” the authors write. “Still, the absolute risk of autism spectrum disorder was less than 5 percent, which is important to take into account when counseling women about the use of valproate in pregnancy.”