Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

Abstract
Objective: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Design: Retrospective population based study. Setting: Population of the Grampian region of Scotland. Participants: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. Results: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). Conclusion: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.