Effect of Antiepileptic Drugs on Fetal Congenital Malformation and Cognitive Function

Lee, Se Jin

Abstract

Although the majority of women with epilepsy give birth to healthy children, intrauterine exposure to antiepileptic drugs (AEDs) increases the risk of fetal major congenital malformations (MCMs), a two-to threefold increase in risk with older AEDs. Several prospective pregnancy registries demonstrated a consistent pattern of increased risk for MCMs with valproate (VPA) used as monotherapy, compared to unexposed populations and to other AEDs. Polytherapy likely increases risk for MCMs, but the risk is more pronounced if VPA was included. There are dose-effect relationships in some AEDs and specific MCMs associated with specific AEDs. Dose-dependent risk for MCMs has been demonstrated with VPA above 800 to 1000 mg. Carbamazepine and VPA have been reported to be associated with a significant increase in the risk of spina bifida. For newer AEDs other than lamotrigine, data are still too limited to determine the risks for MCMs. Fetal exposure to AEDs can produce cognitive deficits. VPA and AED polytherapy probably reduces cognitive outcomes and monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. If possible, avoidance of VPA and AED polytharapy during the first trimester should be considered to decrease the risk of MCMs, and avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes. However these risks must be balanced against potentially grave risks to both mother and fetus posed by seizures. Further studies are needed to compare risks for MCMs and reduced cognitive outcomes of each AEDs at different dosages and combination.