Epilepsy Drug Linked to Autism Risk

Study: Kids exposed to epilepsy drug in utero are more likely to develop autism.

Dec. 2, 2008— -- While a new study that suggests pregnant women who take the epilepsy drug Depakote may increase their babies' risk of developing autism, experts say the usefulness of the drug and the high risk of seizures during pregnancy may outweigh the threat of autism.

Some neurologists believe the finding may one day prove more intriguing for autism research.

The study, published in the journal Neurology, followed 632 children from womb to birth and into childhood between 2000 and 2006. Nearly half the children were exposed to various epilepsy drugs in the womb, while the other half were not.

Statistically, researchers estimate that children who were exposed to the drug sodium valproate were seven times more likely to later develop autism than the children who were not exposed to any epilepsy drug.

Despite the strong finding, the study is actually small: Only nine of the 632 children ended up with an autism diagnosis.

"These findings are only preliminary. More research is needed in this area and into the more general area of autism itself," said Rebecca Bromley, a co-author of the study and an assistant psychologist at the Liverpool and Manchester Neurodevelopment Group at the University of Liverpool in England.

Women who have epilepsy have always faced a special challenge with pregnancy. Neurologists in the United States say that the study raises questions for both parents in the epilepsy community and autism researchers.

"For one, it's a very good drug," said Dr. Michael Goldstein, a vice president of the American Academy of Neurology.

Sodium valproate goes by several names -- valproic acid, depakene and Depakote -- and is commonly used to treat generalized epilepsy and its potentially life-threatening convulsion seizures.

"Prolonged seizure could cause blood flow problems to the baby, which could cause injury," said Goldstein, who is also in practice with Western Neurological Associates in Salt Lake City.

Goldstein said anticonvulsants, especially valproic acid and carbamazepine, have been known to cause "teratogenic malformation," meaning visible birth defects in the limbs.

A Dilemma Treating Epilepsy

According to Goldstein, doctors are aware that some antiseizure drugs can cause abnormalities in the brain.

Goldstein and the makers of the drug say pregnant women with epilepsy often have to choose between the lesser of two risks.

"We generally try to avoid valproic acid in women who might be pregnant," said Goldstein. "But for some women who have difficulty in controlling epilepsy, they're better off taking the medicine than having seizures. The consensus is that seizures are worse for the babies than the medicine."

Abbott, the makers of the brand name valproic acid drug called Depakote, also drives home this point.

"Uncontrolled seizures can cause permanent damage to the brain and for pregnant women can be fatal for both mother and child," said Raquel Powers, a spokeswoman for Abbott.

"The Depakote product label makes it clear that it should not be used as a first line treatment for women of childbearing age," she added. "For many women, however, Depakote may be the only effective seizure medication and that decision should be made between the patient and physician."

At least for Goldstein, the research raised more questions about autism than about the risk of valproic acid.

"There's so much data that valproic acid caused problems with babies that this doesn't change our attitude toward the drug," said Goldstein.

But with this study, "There's an inkling that there may be a specific kind of brain injury resulting from a chemical exposure in utero that causes autism -- that would be more of a surprise and more of a change."

However, Dr. Jacqueline French, a professor of neurology at the New York University Comprehensive Epilepsy Center in Manhattan, believes there are still lessons to be learned about valproic acid.

Changing Treatment to Prevent Autism

"If you think about the fetus developing in the mom, the thing that parents were most worried about was organogenesis --- do the limbs form right, do the fingers form right -- all of those things are completed by the end of the first trimester," said French, who is also a fellow of the American Academy of Neurology.

According to French, that meant that women with epilepsy and their doctors worried more about what drugs were taken at the beginning of a pregnancy and less about which drugs were taken at the end.

"But the brain develops after the first three months and throughout the pregnancy in the womb," said French. She believes research that associates valproic acid with brain development problems, including autism, should change the way neurologists prescribe theses anticonvulsants.

"The word is getting out, but it certainly hasn't gotten out entirely," said French.

Both French and Goldstein assert that women with epilepsy should not be afraid to have children, but that they should consult with their neurologist beforehand.

"A lot of the medications also interfere with birth control for an example," said French. "It takes a lot of expertise and specific knowledge to carry a woman with epilepsy through her childbearing years."