OUTCOMES OF PREGNANCY-ASSOCIATED WITH ANTIEPILEPTIC DRUGS

Objective: To determine whether exposure to antiepilep tic drugs durin g pregnancy is associated with poor fetal outcomes (anomalies and deat h) and to assess the relative risks with phenobarbital, phenytoin sodi um, and carbamazepine. Design: The design was a prospective case-contr ol cohort study of pregnant women with epilepsy and their offspring. O utcomes were compared with those of a control group of 355 healthy wom en and their offspring. Setting: The obstetrics service at Los Angeles County/ University of Southern California Medical Center, Los Angeles , a large, inner-city, teaching hospital. Patients: Two hundred eleven subjects two were pregnant during the years 1987 through 1990, 174 of whom were delivered of infants, were available for analysis. A contro l group of 355 healthy women and their offspring from the same hospita l were randomly selected from a computerized database. Interventions: None. Main Outcome Measure: Anomalies and fetal death were the primary outcome measures. Results: Offspring of women with epilepsy who were exposed to antiepileptic drugs had a higher rate of fetal death and an omalies than did the control population (P=.001). Abnormal outcomes we re associated with the three major antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital). In terms of abnormal outcome (death an d anomalies), phenobarbital was associated with the highest relative r isk, phenytoin with intermediate relative risk, and carbamazepine with the lowest relative risk (P=.019). Numbers were insufficient for asse ssment of risk associated with valproic acid. Conclusion: All three ma jor antiepileptic drugs (phenobarbital, phenytoin, and carbamazepine) are associated with an increased risk of fetal death and anomalies. We found phenobarbital to be most associated with poor pregnancy outcome .