Abstracts

Rationale: In utero antiepileptic drug (AED) exposure is associated with a greater risk of congenital malformations, but data of fetal AED influence on cognitive development are limited and conflicting. The aim of the study was to assess the late effects of fetal AEDs on cognitive development in children at age of 3-6 years.Methods: In this ongoing prospective observational cohort study children aged 3-6 years with fetal exposure to AEDs were included. All mothers of these children were registered in the Georgian National AED-Pregnancy Registry of the European Registry of Antiepileptic Drugs (EURAP). Individuals from the same age range but without fetal AED exposure were enrolled as a control group. In all cases Intelligence Quotient (IQ) using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI – IV), and Wide Range Assessment of Visual Motor Abilities (WRAVMA) tests were assessed. Statistical analyses were performed using SPSS version 20 (SPSS Inc, Chicago, Illinois). A two sample T test was performed to detect differences between means. Probability less than 0.05 was considered as statistically significant. Multiple linear regression with stepwise selection was used to examine the relationship between particular AED exposure (only VPA or only CBZ exposure in all trimesters, or various AEDs used during pregnancy) and IQ. The entry criterion was a p-value <0.05. The exit criterion was a p-value 0.1. An R-Square and standardized β coefficient (β) were calculated.Results: In total 65 subjects were evaluated. Among them 36 (55%) (mean age – 51.6 month; SD 12.6) have experienced AED exposure in utero and remaining 29 (45%) (mean age – 55.4 month; SD 15.7) have not (control group). In 18 (50%) children exposure with valproate (VPA) monotherapy was detected, in 13 (36%) cases with carbamazepine (CBZ ) monotherapy and in 5 (14%) cases exposure with various other AEDs were observed. In overall the mean IQ for exposed population was significantly lower (mean – 83.5; SD – 13.93) than in children of control group (mean – 103.4; SD – 13.91)(t<0.001). Regression analysis showed fetal exposure to VPA (standardized β coefficient (β) = - 0.576; p<0.001), CBZ (β= - 0.394; p=0.001) as well as other AEDs (β= - 0.324; p=0.004) to be associated with decreased IQ in individuals with fetal exposure compared to those without it. The R-squared coefficient was equal to 0.352 for the final model.Conclusions: Results suggest that in utero AEDs exposure can impair cognitive development of individuals. Fetal VPA exposure seems to be correlated with more expressed cognitive decline if judged against CBZ or other AEDs. The R square value indicates that more than 35% of reduced cognitive abilities could be explained by the fetal AEDs exposure. More data are needed to be analyzed to define other factors associated with cognitive impairment in children with AEDs exposure. The study is performed within scientific grant of the Shota Rustaveli National Scientific Foundation (FR/373/8-313/13)