Antiepileptic drugs and neurodevelopment

Clinical studies have documented the teratogenic potential of antiepileptic drugs (AEDs). More recent cohort studies have been trying to sort out which AEDs impose the highest risk of teratogenicity. Currently, there is evidence demonstrating an increased risk of major congenital malformations (MCMs) for valproate, phenobarbital, and polytherapy during pregnancy. Based on the current data from multiple studies, the risk for valproate is the highest. Additional studies are needed to fully delineate if differences exist for other AEDs, especially the newer AEDs. However, although MCMs are easy to recognize and have been shown to be more common after in utero exposure to AEDs, there are insufficient data regarding their long-term effects on cognition and behavior in exposed children. Although most children born to women with epilepsy are healthy, in recent years there has been increasing awareness of the long-term effects of in utero exposure to AEDs. Recent discovery of neuronal apoptosis following in utero AED exposure in animals during a period that corresponds to the third trimester and early infancy in humans raises further concerns. Prospective clinical studies seem necessary in order to better understand the long-term neurodevelopmental effects of in utero exposure to AEDs.