A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy

ObjectiveTo investigate the differential effects of fetal exposure to antiepileptic drugs (AEDs) on cognitive fluency and flexibility in a prospective sample of children.MethodsThis substudy of the Neurodevelopmental Effects of Antiepileptic Drugs investigation enrolled pregnant women with epilepsy on AED monotherapy (carbamazepine, lamotrigine, and valproate). Blinded to drug exposure, 54 children were tested for ability to generate ideas in terms of quantity (fluency/flexibility) and quality (originality). Forty-two children met inclusion criteria (mean age = 4.2 years, SD = 0.5) for statistical analyses of drug exposure group differences.ResultsFluency was lower in the valproate group (mean = 76.3, SD = 7.53) versus the lamotrigine (mean = 93.76, SD = 13.5, ANOVA P < 0.0015) and carbamazepine (mean = 95.5, SD = 18.1, ANOVA P < 0.003) groups. Originality was lower in the valproate group (mean = 84.2, SD = 3.23) versus the lamotrigine (mean = 103.1, SD = 14.8, ANOVA P < 0.002) and carbamazepine (mean = 99.4, SD = 17.1, ANOVA P < 0.01) groups. These results were not explained by factors other than AED exposure.ConclusionChildren prenatally exposed to valproate demonstrate impaired fluency and originality compared with children exposed to lamotrigine and carbamazepine.