Reducing birth defects in women with epilepsy: Research leading to results

Merely 20 years ago, a report of the Quality Standards Subcommittee of the American Academy of Neurology recommended that antiepileptic drug (AED) selection for pregnant women with epilepsy should be based on the AED “deemed most appropriate for her seizure type.” Scientifically, lumping all AEDs together when chemical structures and mechanisms of action differ greatly was questionable, but the evidence for differential effects on fetal outcomes was sparse. Multiple research studies have now made it clear that the level of risk for major congenital malformation (MCMs) differs substantially among AEDs. The prevalence of MCMs is highest with valproate monotherapy compared to other monotherapies, and includes neural tube defects, heart malformations, cleft palate, hypospadias, and polydactyly. Likewise, the prevalence of MCMs is higher in polytherapy combinations that include valproate, compared to polytherapies that exclude valproate. MCM rates with some AED monotherapies even approximate the rates in the general population (e.g., levetiracetam, lamotrigine).