Researchers in the U.S. and U.K. are conducting an ongoing investigation of the cognitive effect of fetal exposure across four commonly used antiepileptic drugs (AEDs) as part of an NIH-funded Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study. An early NEAD analysis found that fetal exposure to valproate impairs IQ at age three. A new analysis, reported today at the 65th annual meeting of the American Epilepsy Society (AES), reveals that this adverse effect on IQ persists to age six. (Platform B.01)
The analysis is based on pregnant women with epilepsy on AED monotherapy enrolled in the NEAD Study from 1999 to 2004. The purpose of the study is to determine if there are differences in long-term neurodevelopmental effects among carbamazepine, lamotrigine, penytoin, or valproate. Child IQ was lower with valproate exposure compared to each of the other AEDs.
In the present study, adjusted mean IQs for each AED were: carbamazepine 105, lamotrigine 108, phenytoin 106, and valproate 99. IQ was negatively associated with valproate dose; however, a similar relationship was not found with the other AEDs.
The children's IQ was measured by the Differential Ability Scale (DAS), including a secondary analysis of Verbal and Non-verbal Cluster scores from the DAS. Verbal abilities were less than non-verbal abilities across all AEDs combined and individually for carbamazepine, lamotrigine and valproate.
"Further investigation is needed to confirm if the verbal impairments across this study occur in a different cohort," says lead investigator Kimford J. Meador, M.D. "Research is also needed to delineate the cognitive effects of fetal exposure to other AEDs, and to determine the mechanisms underlying these effects."
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