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Anticonvulsant Drugs Are Teratogens

How to treat pregnant women with epilepsy remains an enigma. Should anticonvulsant medication be continued during pregnancy, or should medication be stopped or switched? Are some anticonvulsants more easily tolerated than others? Does use of several anticonvulsants put the fetus in greater danger? Should women with nonepileptic disorders -- e.g., migraine or bipolar disease -- be treated with anticonvulsants (a strategy that is currently all the rage)? Finally, what causes fetal abnormalities in pregnant women with seizures? Is it the condition itself or the drugs used to treat it? The current study answers only one of these questions, albeit in an emphatic manner.

Screening 128,000 women at delivery, the authors identified 3 groups of infants: those exposed to anticonvulsants prenatally, those born to women with a seizure history who had not taken anticonvulsant drugs during pregnancy, and those with no maternal seizure history and no exposure to anticonvulsant drugs (controls). Infants exposed to one anticonvulsant prenatally were more likely to exhibit major complications (including malformations, hypoplasias of the face and fingers, microcephaly, and small body size) than were controls (20.6 percent vs. 8.5 percent, respectively). Among infants exposed to two or more anticonvulsants, the frequency of embryopathology was even higher (28.0 percent). The authors conclude that the use of anticonvulsants during pregnancy -- not the presence of epilepsy itself -- produces a distinctive pattern of somatic abnormalities. The anticonvulsants most commonly used in this cohort were phenytoin, carbamazepine, and phenobarbital.

Comment: These results clearly support the position that pregnant women with epilepsy should be withdrawn from anticonvulsants, if feasible. Often this will not be possible: Anticonvulsants usually must be continued so that seizures are controlled. Further, this study does not address environmental factors or personal habits in pregnant women with epilepsy. The roles of alcohol, cigarettes, and illicit drugs are not considered. And no mention is made of newer antiepileptic drugs. Most of the questions posed above were not addressed in this paper.

— DJ Dalessio

Donald J. Dalessio, MD, is Consultant in Neurology, Scripps Clinic, La Jolla, CA.

Published in Journal Watch Neurology June 8, 2001

Citation(s):

Holmes LB et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001 Apr 12 344 1132-1138.

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