Women who use the epilepsy drug topiramate (Topamax) during pregnancy are at risk for having a baby with a serious birth defect, investigators report in the journal Neurology.
Topiramate is licensed for use to treat certain seizures and for prevention of migraine, Dr. John Craig, at the Royal Group of Hospitals in Belfast, UK, and co-authors note. Topiramate has been shown to cause birth defects in animal studies, but safety data in human pregnancy have been limited.
Craig's group therefore analysed data from the UK Epilepsy and Pregnancy Register for 203 pregnancies, of which 178 resulted in live birth.
Of 31 abnormalities (17,4 percent) that occurred, 16 were major malformations (nine percent). Three of these were in women who received topiramate only and 13 were in women treated with a multi-drug regimen.
The highest rates of major malformations occurred when topiramate was combined with valproate, either as dual therapy or in a regimen of three or more antiepileptic drugs. The rate of malformations for drugs and drug combinations that did not include valproate was 8,4 percent.
In particular, the authors note, the rate of cleft palates and other oral clefts was 11-times higher than that seen in the general population. The rate of hypospadias - abnormal opening of the penis - was 14-times higher.
Clearly, these findings need to be replicated in larger studies from different databases before women of child-bearing age are counselled against using combinations including topiramate and valproate, Craig and his colleagues note.
Nevertheless, they advise monitoring the pregnancies of women with migraine or epilepsy who have been exposed to topiramate.