Major birth defects tied to common epilepsy drug

NEW YORK (Reuters Health) - The safety of a popular drug for seizures took another hit Wednesday when researchers pinned a handful of major birth defects on the medication.

Earlier research had shown that taking Depakote (valproate) during pregnancy might lower the baby’s IQ and lead to deformities in up to one in ten cases. (See Reuters Health story April 16, 2009.)

Scientists have long known about one of these malformations, called spina bifida, in which the fetus’ spinal column doesn’t close properly. But it was unclear whether the drug was linked to other birth defects, such as heart problems or extra short limbs.

Writing in the New England Journal of Medicine, European researchers report an increased risk of six different birth defects in babies whose mothers took Depakote during their first trimester of pregnancy.

The odds of spina bifida, for instance, were more than 12 times higher in these babies compared to those whose mothers didn’t take epilepsy drugs. Abnormal skull development, cleft palate, holes in the heart’s walls, extra fingers or toes, smaller limbs, and urinary problems were also more frequent in the Depakote group, with odds increased up to seven times.

And five of these defects appeared to be specific to Depakote compared with other epilepsy drugs.

Still, the researchers note, the actual frequency of specific birth defects were relatively small, all ranging below one percent. That compares to an overall rate of all birth defects of about 2 percent in the general population.

“I would say valproate is a poor first choice for pregnant women with epilepsy,” said Dr. Kimford J. Meador, a seizure disorder expert at Emory University in Atlanta, who wasn’t involved in the study.

Since last summer, U.S. guidelines have recommended against using Depakote in pregnancy, but Meador said it was still widely used across the country.

Although a few women with epilepsy may only respond to Depakote, often there are alternatives. “If a drug doesn’t work on a woman, you can try another,” said Meador. But fixing malformations is more of a challenge.

Depakote is also approved by the US Food and Drug Administration for the treatment of psychiatric conditions such as bipolar disorder. For women taking the drug, Meador said they should start considering switching medication before they think about having kids.

“By the time they find out they are pregnant, it’s probably too late,” he said.

SOURCE: NEJM/New England Journal of Medicine, June 9, 2010.