Practical management of epilepsy and pregnancy

Abstract

The goal of the management of epilepsy during pregnancy is to maintain control of in particular major convulsive seizures with minimal exposure the fetus to potentially teratogenic drugs. We have learned that antiepileptic drugs (AEDs) differ in their teratogenic potential. In particular, valproate has been associated with greater risks for major congenital malformations and adverse effects on the child’s cognitive and behavioral development. Valproate should therefore, whenever possible, be avoided in pregnancy, and regulatory bodies, such as EMA, have issued restrictions on its use in women of childbearing age. Topiramate has been associated with impaired intrauterine growth, and there are signals of increased risk for malformations with this drug. In general, teratogenic risks appear to be dose-dependent and the aim should be to established the lowest effective dose before pregnancy, regardless of which AED that is used. Many AEDs undergo pronounced changes in their pharmacokinetics during pregnancy, resulting in significant decline in the serum concentration with associated risk of deterioration in seizure control. This is particularly pronounced for lamotrigine, but seen also with oxcarbazepine and levetiracetam. Drug level monitoring is therefore often recommended during pregnancy. The value of this is increased if the optimal serum concentration has been documented before pregnancy to serve as an individual reference and target concentration. Whether a decline in serum concentrations as such during pregnancy should prompt a dose increase, or if this should be considered only in case of loss in seizure control, is still debated.