Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register

Epilepsy is the most common serious chronic neurological condition, with a prevalence of between 4 and 10 people per 1000. ¹ Most of those affected, including women of childbearing age, will require long term treatment with antiepileptic drugs (AEDs) to prevent seizures. Although the interactions between epilepsy and pregnancy are multiple, it is the potential effect of AEDs on the developing fetus that raises most concern. With an estimated three to four pregnancies in every thousand occurring to women with active epilepsy, ^{2, 3} this means between1800 to 2400 children are born to such women in the United Kingdom each year.

It is widely accepted that prenatal exposure to AEDs increases the risk of a major congenital malformation (MCM) from the background risk of 1-2% ^{3, 4} to 4-9%. ^{4- 7} With regard to the spectrum of MCM, physicians are generally aware that neural tube defects have been associated with in utero exposure to sodium valproate and carbamazepine ^{8, 9, 10} and barbiturates (phenobarbitone (phenobarbital), primidone) and phenytoin have been associated with congenital heart defects and facial clefts. ^{11- 13} Other MCMs, including urogenital and skeletal abnormalities, have also been reported. ^{13, 14}

The information from these studies, which form the basis for how we counsel women with epilepsy who are contemplating pregnancy or who are already pregnant, did not until recently include any data on the newly available AEDs, of which eight (vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, and pregabalin) have been introduced in the UK since 1989. While animal studies on many of these AEDs are encouraging in comparison with the earlier ones, ¹⁵ human data are sparse. In an attempt to provide information on the risks of MCMs for prenatal exposure to the ever increasing number of AEDs, pregnancy registries have been developed. The UK Epilepsy and Pregnancy Register, established in 1996, was one of the first modern independent pregnancy registers to be established. Here we present our findings up to March 31 2005.

METHODS

This is a prospective, observational, registration and follow up study which began in December 1996. Ethics approval was obtained from the North Thames multicentre research ethics committee and subsequently from all UK local research ethics committees.

Cases suitable for inclusion were defined as pregnant women with...