Cognitive functions in children exposed to antiepileptic drugs in utero - Study in Georgia

•Fetal exposure to valproate associated with poorer cognitive performance in child•Adverse effects of valproate were dose-dependent.•Mothers with epilepsy had lower IQ than control mothers confounding associations.•Breast-feeding was associated with significantly higher IQ in infant.

ObjectiveThe cognitive teratogenicity of antiepileptic drugs (AEDs) has gained increasing attention in the last decade. The objective of the current study was to assess the effects of AED fetal exposure on the cognitive development of children of mothers with epilepsy from Georgia in a controlled study taking into consideration major confounding factors.MethodsA prospective cohort group was formed from children and mothers registered in the Georgian National AED-Pregnancy Registry. The study group's age- and gender-matched control children without fetal AED exposure were selected retrospectively. The Intelligence Quotient (IQ) using the Wechsler Adult Intelligence Scale - revised (WAIS-R) was assessed in mothers. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-4) were used to assess intellectual functioning for children of both study and control groups. Linear regression analysis was performed to detect association of AED exposure on the cognitive performance of children.ResultsIn total, 100 children aged 36 to 72 months were evaluated. The IQ of WWE was significantly lower compared to women without epilepsy in all modalities. Exposure to valproate (VPA) (n = 18) was associated with lowest cognitive performance regarding Full Scale IQ (FSIQ) (β, − 12.04; p = 0.006) and verbal comprehension (VCI) (β, − 8.89; p = 0.019). Maternal FSIQ, maternal performance IQ (PIQ), and child's age at first phrases were independent factors associated with the cognitive development of children.ConclusionsMultivariate analysis showed VPA to be an independent predictor for decreased cognitive performance. Maternal FSIQ, PIQ, and child developmental achievements were significant confounders for cognitive performance in children.