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Outcomes of pregnancy associated with antiepileptic drugs
C H Waters1, Y Belai, P S Gott
1Department of Neurology, University of Southern California, School of Medicine, Los Angeles.
Objective:
To determine whether exposure to antiepileptic drugs during pregnancy is associated with poor fetal outcomes (anomalies and death) and to assess the relative risks with phenobarbital, phenytoin sodium, and carbamazepine.
Design:
The design was a prospective case-control cohort study of pregnant women with epilepsy and their offspring. Outcomes were compared with those of a control group of 355 healthy women 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 who were pregnant during the years 1987 through 1990, 174 of whom were delivered of infants, were available for analysis. A control group of 355 healthy women and their offspring from the same hospital were randomly selected from a computerized database.
Intervention:
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 anomalies than did the control population (P = .001). Abnormal outcomes were associated with the three major antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital). In terms of abnormal outcome (death and anomalies), phenobarbital was associated with the highest relative risk, phenytoin with intermediate relative risk, and carbamazepine with the lowest relative risk (P = .019). Numbers were insufficient for assessment of risk associated with valproic acid.
Conclusion:
All three major 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.