A discussion of the teratogenicity of antiepileptic drugs (AEDs) may be found elsewhere.4 In general, women who take AEDs have double the risk of bearing a malformed infant as women who do not take AEDs. Features of the fetal anticonvulsant syndrome include limb abnormalities, craniofacial abnormalities, and growth and development abnormalities.
The risk to the fetus increases significantly if a pregnant woman takes multiple AEDs. The risk also is higher for women with a personal or family history of birth defects or miscarriages due to birth defects.
Any woman who is physically capable of becoming pregnant should be counseled on these issues and should be encouraged to take folic acid, 0.4 mg per day. Folic acid intake is particularly important before conception and should continue throughout pregnancy. Women with a previous pregnancy complicated by a fetal malformation, such as a neural tube defect, and women with a family history of birth defects should take 4 mg per day of folic acid and probably should avoid valproate and carbamazepine.
Congenital malformations have been reported in association with all the older AEDs. Valproate appears to carry a particular risk of neural tube defects.
Experience with the newer AEDs (such as felbamate, gabapentin, and lamotrigine) has not been extensive enough to determine risk. Unfortunately, there are no carefully controlled studies to identify which of the AEDs are safest for the fetus. Therefore, in general, the best approach is to select an AED on a case-by-case basis, looking for one that will control seizures (especially generalized seizures) and to administer it at the minimum effective dosage. In every case, the physician must weigh the risk/benefit ratio.
Reviewed and revised December 2003 by Steven C. Schachter, MD, Harvard Medical School
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