Birth defect risk fairly low with epilepsy drugs

NEW YORK (Reuters Health) - Among infants exposed to antiepileptic drugs (AEDs) in pregnancy, almost 96 percent are born free of major congenital malformations, according to a report in the Journal of Neurology, Neurosurgery, and Psychiatry. However, there are differences between AEDs, the study indicates.

Dr. James I. Morrow from Royal Victoria Hospital, Belfast, UK and colleagues used the UK Epilepsy and Pregnancy Register to evaluate the relative risk of major congenital malformation in 2,598 pregnant women with epilepsy exposed to a single AED, 770 exposed to more than one AED, and 239 epileptic women who were not exposed to any AED.

The overall rate of major congenital malformations was 3.5 percent among women who did not take any AED during pregnancy and 4.2 percent among women who took AEDs, the investigators report.

The rate among women who took more than one AED increased to 6.0 percent, significantly higher than the 3.7 percent rate seen with only one drug.

Treatment with carbamazepine was associated with a low rate of major congenital malformations (2.2 percent), the results indicate, while the highest rates were associated with valproate (6.2 percent) and topiramate (7.1 percent).

No major congenital malformations were observed with single-drug treatment with levetiracetam, ethosuximide, clonazepam, vigabatrin, oxcarbazepine, or piracetam.

Combinations containing valproate were associated with higher rates of major congenital malformations than were combinations without valproate, the researchers note, and no major congenital malformations were occurred in pregnancies exposed to the combination of carbamazepine and lamotrigine.

The rate of major congenital malformations was not dose related for carbamazepine or valproate, the investigators say, but major congenital malformations were more often associated with high doses of lamotrigine than with lower doses of this drug.

The types malformations associated with single-drug therapy with carbamazepine, valproate or phenytoin treatment were similar to those previously reported, the researchers note. "For lamotrigine, the types of major congenital malformations were not dissimilar from other AEDs, although genitourinary abnormalities and unusual gastrointestinal defects appeared to be over represented."

"Our study supports the idea that there are differences between AEDs and highlights areas of concern," the authors conclude. "That almost 96 percent of infants born to women with epilepsy did not have a major congenital malformation, however, is a message that is likely to be reassuring both to women with epilepsy and to those who care for them."

"Larger numbers of pregnancies are required to strengthen confidence in the power of these observations," writes Dr. M. J. Brodie from Western Infirmary, Glasgow, Scotland in a related editorial. "The hope too is that there will be consistency across the different data sets. All this activity has the potential to provide useful guidance for doctors treating young women with epilepsy."

SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, March 2006.