Adverse Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medications An Ever-Expanding Story

The spectrum of teratogenic effects of antiseizure medications (ASMs) has expanded considerably since Meadow's description in 1968 of harelip, cleft palate, and other abnormalities in babies born to mothers taking primidone, phenytoin, trimethadione, or phenobarbital.(1) In particular, the past 2 decades have seen major progress in uncovering the adverse effects of prenatal exposure to certain ASMs on postnatal neurodevelopment. Those linked to valproate use in pregnancy have been well documented and range from impairments in cognitive development such as reductions in IQ and deficits in language and executive function, to increased risks of neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and intellectual disability.(2-5) Growing evidence points to exposure to topiramate also carrying increased risks of adverse postnatal neurodevelopmental outcomes, including ASD and intellectual disability.(4) For valproate and topiramate, these adverse effects seem to be dose-dependent, with higher doses being associated with poorer outcomes.(4) Data on the neurodevelopmental outcomes of children exposed in utero to most of the other ASMs, including the majority of newer agents, are scarce or lacking altogether. Moreover, the impact of prenatal ASM exposure on neurodevelopmental domains other than those mentioned above remains largely unexplored.