Memory dysfunction in school-aged children exposed prenatally to antiepileptic drugs

Objective: Prenatal exposure to antiepileptic drugs (AEDs) and in particular valproate (VPA) has been shown to impair intellectual and language development in children, but the impact on memory functioning has not been thoroughly investigated. This study aimed to evaluate memory skills in school-age children who were exposed to AEDs prenatally. Method: The sample comprised of 105 children aged 6 to 8 years. Information on AED exposure, maternal epilepsy, pregnancy, and medical history was prospectively obtained. Children completed a neuropsychological assessment including measures of verbal and nonverbal memory. Results: Children exposed to VPA performed lower than expected on list learning, story recall, and figure recall tasks. Those exposed to VPA in a polytherapy regime achieved poorer verbal memory scores compared with other drug exposure groups. VPA dose was negatively correlated with both verbal and nonverbal memory measures. Language ability predicted performance on all verbal memory measures and VPA dose was an additional predictor of retroactive interference on the list learning task. Performance on figure recall was predicted by exposure to VPA in polytherapy. Children exposed to carbamazepine (CBZ) also showed a higher rate of impairment on nonverbal memory measures. Conclusion: Both verbal and nonverbal memory skills are at risk in children exposed prenatally to VPA, particularly in those exposed to higher VPA doses. There may also be a selective vulnerability of the medial temporal lobe to VPA exposure. Our data highlight the possibility that nonverbal memory may also be affected in children exposed to CBZ. These findings have significant implications for the provision of cognitive and educational strategies to children exposed to AEDs in utero.