Spina Bifida in Infants of Women Treated with Carbamazepine during Pregnancy

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Abstract
SHORTLY after Robert and Guibaud reported in 19821 an association between the use of valproic acid during pregnancy by women with seizure disorders and the occurrence of spina bifida in their offspring, carbamazepine was also implicated, on the basis of 12 cases of spina bifida among 60 infants with birth defects after exposure to carbamazepine in utero.2 , 3 Jones et al. recently reported the outcomes of pregnancy in a cohort of 56 women taking carbamazepine, on the basis of the data from the California Teratogen Registry.4 This study included a case of spina bifida. In follow-up correspondence, Jones et al. mentioned that I had identified eight cases of spina bifida in infants whose mothers had taken carbamazepine during pregnancy in a review of published and unpublished cohort studies of the use of anticonvulsant agents during pregnancy.5 As of 1990, the Food and Drug Administration had reports of 64 cases of spina bifida associated with maternal exposure to carbamazepine, of which 36 were not confounded by concurrent exposure to valproic acid. These were among a total of 237 reports known to the FDA ( Table 1 ) of infants with spina bifida whose mothers took antiepileptic agents during pregnancy. The reports included both domestic and foreign isolated case reports, cases compiled by birth-defect registries, and cohort studies of women taking antiepileptic agents during pregnancy. Only 15 cases of spina bifida were reported in infants whose mothers had followed antiepileptic regimens containing neither valproic acid nor carbamazepine during pregnancy. Six other cases were reported after maternal exposure to "antiepileptics other than valproate," so it was not known whether these cases involved exposure to carbamazepine.3