Hunt and colleagues recently published the preliminary experience from the UK Epilepsy and Pregnancy Register (Neurology 2008;71:272-6). Their findings were based on 203 women with epilepsy who became pregnant while taking topiramate (Topamax) either as monotherapy or in combination with other antiepileptic drugs (AEDs). Three major congenital malformations were observed in 70 monotherapy exposures (4.8%) and major congenital malformations occurred in 11.2% of polytherapy exposures.

This article highlights the potential risk of all antiepileptic drugs to cause major congenital malformations in the children of women who take these medications during pregnancy. Specifically, this study looked at the incidence of these malformations in children exposed to topiramate monotherapy in utero and found that 4.8% were affected. This is increased related to the rate in the general population (1-2.5%) and may be higher than the incidence of malformations in children of mothers exposed to some other antiepileptic drugs, yet lower than the incidence of malformations with other drugs such as valproic acid. Also, the study found that 11.2% of fetuses exposed to topiramate as part of a polydrug antiepileptic drug regimen had major malformations. This confirms a large body of evidence that polytherapy increases the risk of major malformations.

The information also emphasizes the need for all women of childbearing years who take antiepileptic drugs to discuss preconception planning with their physician. All women should clearly understand the risks and benefits of their therapy. Until more information is available, topiramate use in women who plan on conceiving should be restricted to those in whom the drug is definitely needed for seizure control or other indications; also, the mother should be informed of the potential risks to her child.

Submitted on July 28, 2008
Edited by Steven C. Schachter, MD