Verbal and non-verbal cognitive abilities were assessed at 3 years of age in 216 children exposed in utero to commonly used antiepileptic drugs. The investigation was an ongoing prospective multicenter study in the USA and UK, involving pregnant females with epilepsy on monotherapy with carbamazepine, lamotrigine, phenytoin or valproate, from 1999 to 2004. Tests included Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal scores were lower than non-verbal in children exposed to each drug. They were higher if mother received preconceptional folate. Valproate was associated with poorer cognitive outcomes, both verbal and non-verbal, and the negative effect was dose related. Carbamazepine had a negative, dose related effect on verbal performance. Effects of lamotrigine and phenytoin on cognitive performance were not dose related. Fetal AED exposure may alter language development and normal cerebral lateralization. Preconceptional folate may improve cognitive outcomes. [1]

COMMENT. This study provides further evidence of the adverse cognitive outcome in young children exposed to some common AEDs in utero, and the negative dose related effects on both verbal and non-verbal performance associated with fetal valproate exposure. These findings are in contrast to the absence of delayed cognitive performance in children exposed in utero to levetiracetam.