Abstracts

Antiepileptic drugs (AEDs) can produce behavioral teratogenesis in animals at dosages less than required to produce anatomical teratogenesis. We sought to evaluate the cognitive effects of in utero AED exposure in humans in order to determine if differences exist across commonly prescribed AEDs., The NEAD Study is an ongoing prospective multicenter observational investigation, which enrolled pregnant women with epilepsy taking monotherapy carbamazepine (CBZ), lamotrigine(LTG), phenytoin (PHT), or valproate (VPA). The long-term goal of the study is to examine children from these pregnancies at 6 years old to determine if differential neuropsychological effects exist from in utero exposure across the four most commonly employed AEDs in pregnant women. This analysis is based on currently available results at 2 years old from the Mental Scale of the Bayley Scales of Infant Development for 166 children (CBZ=43, LTG=57, PHT=38, VPA=28). The childrens[apos] Mental Developmental Index (MDI) scores were analyzed by Analysis of Covariance controlling for maternal IQs., Children exposed in utero to valproate had lower MDI scores at 2 years of age compared to the other 3 AEDs (p=.028). Follow-up pairwise comparisons revealed a significant difference for VPA-LTG (p=.018) and a trend for VPA-CBZ (p=.056). Mean (SD) MDIs were: CBZ=94 (15), LTG=97 (17), PHT=90 (19), VPA=85 (19). The percentages of children with MDI [lt]70 for each AED were: CBZ=12%, LTG=11%, PHT=13%, VPA=25%. The adverse effect of VPA was related to anticonvulsant blood level (p=.0001)., These findings in conjunction with prior studies imply that in utero valproate exposure is more likely than other commonly used AEDs to impair cognitive development. Thus, valproate poses a greater risk for the unborn child for behavioral as well as anatomical teratogenesis. Additional studies are needed to confirm the present findings and to delineate the risks for other AEDs., (Supported by NIH/NINDS #2RO1 NS38455.)