British researchers report in the July 22 issue of the journal Neurology that pregnant women who use epilepsy drug Topamax (topiramate) alone or in combination with other epilepsy drugs could be at greater risk of giving birth to children with certain physical defects.

Topamax is a common anti-seizure medication used by many with epilepsy and migraines. The drug received a pregnancy category C classification from the US Food and Drug Administration, meaning that it hasn’t been studied in pregnant women, though it appears to cause harm in the fetus in animal studies. US prescribing information read that the drug caused birth defects, miscarriages, and decreased fetal weight in rabbit, rats, and mice.

For the study, lead researcher John Craig of the Royal Group of Hospitals In Belfast, Northern Ireland and colleagues analyzed data on 203 women who became pregnant while taking Topamax alone or in combination with other drugs. Of the 203 pregnancies, 18 ended in spontaneous abortions, 2 in stillbirths and 5 in induced abortions.

From a total of 178 newborn babies, 16 (4.8 percent) suffered from major birth defects. Three of these babies had mothers taking Topamax alone, while the mothers of the other 13 babies were taking Topamax plus other epilepsy drugs. Four of the babies had cleft palettes or cleft lips, which represents a rate 11 times higher than one would expect among women not taking the drug (1 in 500), the researchers said.

Four baby boys had genital defects, two of them being classified as “major defects.” The number represents a rate 14 times higher than normal (1 in 300), Dr. Craig’s team reported.

Overall, the findings showed that more birth defects occurred in women taking Topamax along with the drug valproate, or valproic acid, than in women taking Topamax and another epilepsy drug. Previous research has shown that valproate is linked to a high risk of birth defects.

Although the study was small, it was the first to link Topamax to birth defects in humans, thus confirming the animal studies. The findings need to be confirmed with other studies in order to have clear answers, Dr. Craig said.

“More research needs to be done to confirm these results, especially since it was a small study. But these results should also get the attention of women with migraine and their doctors, since topiramate is also used for preventing migraine, which is an even more common condition that also occurs frequently in women of childbearing age,” Dr. Craig said.

Topamax has become the most widely prescribed drug for preventing migraines since its FDA approval for this condition, the researchers said. Also, women are three times more likely to experience migraines than men are and women in their childbearing years are particularly vulnerable.

That’s why the American Academy of Neurology urges women who think of becoming pregnant and experience migraines to reconsider treatment with Topamax.

“Migraines can be quite debilitating for the mother, but they do not generally pose a risk to a fetus,” neurologist Shlomo Shinnar, MD, PhD, of New York’s Montefiore Medical Center and a spokesman for the American Academy of Neurology told WebMD.

As for women with epilepsy, they should be closed monitored by their health care providers and continue their treatment for epilepsy, as uncontrolled seizures pose risk to the fetus as well. More over, the women should be warned about the potential side effects of Topamax.

The study was supported by a grant from the Epilepsy Research Foundation and also by educational grants from GlaxoSmithKline, UCB Inc., Sanofi-Aventis, Janssen-Cilag, Eisai and Pfizer.