Another Study Links Autism to Epilepsy Drug

by Aalok Mehta

March 4, 2009

New research suggests that a mother’s use of the anti-epilepsy drug sodium valproate during pregnancy may increase the risk of autism spectrum disorders in her child. But experts say that the reports, while intriguing, look at small numbers of people and should be considered highly preliminary.

Many of the nearly two dozen drugs now approved to treat epilepsy are known to increase the risk of birth defects such as spina bifida. For valproate and similar drugs, the rate can be as much as six times higher than normal.

Based on a small survey, Gus Baker, a professor of clinical neuropsychology at the University of Liverpool, and his colleagues suspected that valproate might increase the incidence of behavioral disorders in children as well.

Their first step was to solicit, from 242 mothers with epilepsy, assessments on their children’s behavior. “Mothers exposed to sodium valproate were more likely to have children with development delay when compared to other drug exposures,” Baker says of the retrospective study, published Dec. 2 in the journal Epilepsy and Behavior.

Knowing that studies of self-reported behavior can be biased, Baker next organized a prospective study of 620 mothers, half with epilepsy and half without. Though the full study, which began in 2000, won’t be completed until 2010, Baker and colleagues from the Liverpool and Manchester Neurodevelopment Group thought the preliminary results were interesting enough to warrant publication.

Writing in the Dec. 2 issue of Neurology, Baker and his colleagues report that among the offspring of 64 mothers who had taken valproate during their pregnancy, four children were diagnosed with an autism spectrum disorder. Compared with the three autistic children from the 336 children in the healthy-mother group, this was a sevenfold rate increase, Baker reports. No other epilepsy drug was linked with such an uptick.

“The important message is that some anti-epileptic drugs may carry risk to the unborn child and that women with epilepsy considering having a family should receive pre-conceptual counseling with their physicians about those risks,” Baker says. “We do not believe, however, that women are routinely receiving pre-conceptual counseling and hope that this research along with other published reports raises the importance of informing women about risks of pregnancy.”

The studies are interesting because valproate is a very useful drug, says Andre Lagrange, an assistant professor of neurology at Vanderbilt University who was not involved in the research. In many cases, an alternate drug with fewer side effects and a lower chance of birth defects, such as lamotrigine (Lamictal), works for patients. But for some, valproate is the only drug to properly control seizures. In addition, it is commonly used to treat people with mood or psychiatric disorders.

Even the final results of Baker’s study are likely to offer too little information to provide firm answers. “This is an important question, but the results are very preliminary,” Lagrange says. “This preliminary [Neurology] study suggests a trend, but it is far from an adequate sample size.”

Still, Lagrange agrees that doctors need to offer more counseling. He also recommends that in some cases doctors discuss such issues with their teenage patients.

“Given the known risk of anti-epileptic drugs, I really agree that we need to be doing a better job about counseling our patients about possible birth defects,” he says. “The risk of neurobehavior problems is concerning; however, the data is far from conclusive."