The frequency of neonatal morbidity after exposure to antiepileptic drugs in utero: a retrospective population-based study.

Objectives: To investigate the frequency of malformations, fetal growth retardation, cerebral hemorrhage and neonatal withdrawal symptoms in newborns exposed to antiepileptic drugs (AEDs) in utero.

Design: Population of the northeastern part of Slovenia (pregnant women and newborns between 1998 and 2002).

Methods: Data on newborns born between 1998 and 2002 of 37 epileptic mothers taking AEDs in pregnancy, of 32 epileptic mothers not taking AEDs in pregnancy and of 211 mothers healthy in pregnancy were ascertained from hospital obstetric and neonatal records and included in the study. The health status of 270 newborns was assessed.

Main Outcome Measures: frequency of congenital malformations, growth retardation (SFD), intracranial hemorrhage, feeding problems and withdrawal symptoms.

Results: In the group not exposed to antiepileptic drugs (32 neonates), two (2.9%) had germinal matrix hemorrhage grade I, one (1.4%) was small for date (SFD) and one (1.4%) had feeding problems. In the group exposed to antiepileptic drugs (37 neonates), nine (13%) had germinal matrix hemorrhage grade I, six (8.6%) were SFD, five (7.24%) had feeding problems, four (5.8%) had withdrawal symptoms and three (4.3%) "macro" congenital anomalies. Among neonatal problems in the control non-exposed group of newborns of 211 healthy women we identified 23 (10.9%) newborns who were SFD, 5 (2.4%) cases with germinal matrix hemorrhage grade I, 5 (2.4%) cases with major congenital malformations and 7 (3.3%) cases with feeding problems.

Conclusions: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with increased risk of neonatal morbidity. In our study a particularly significant connection was established between carbamazepine therapy during pregnancy and cerebral hemorrhage in the neonates.