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The teratogenicity of anticonvulsant drugs: a progress report
  1. L B Holmes
  1. Genetics and Teratology Unit, Pediatric Service, Massachusetts General Hospital, Warren 801, 55 Fruit Street, Boston, MA 02114-2696, USA
  1. Correspondence to:
 Dr L B Holmes;

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Antiepileptic medication in pregnancy

Exposure to anticonvulsant drugs during pregnancy is one of the most common potentially teratogenic exposures, occurring in 1 in 250 (0.4%) of pregnancies in a recent study in Boston.1 The teratogenicity of these drugs was first postulated in the 1960s, with a consensus developing in the 1970s that a distinctive anticonvulsant embryopathy was produced. Two theories developed as to the cause: (1) the mother's underlying epilepsy2 and (2) the anticonvulsant drug.3

All anticonvulsants marketed up to 1976 have been shown to be teratogenic, with varied manifestations and degrees of severity. Hopefully some of the “new” anticonvulsants marketed in the 1990s, for example, gabapentin (1993), lamotrigine (1994), and topiramate (1996), will be shown not to be teratogenic.


I define a teratogenic effect as any harmful fetal effect from an exposure during pregnancy. Some effects are apparent at birth and others at older ages. The most common abnormalities identified in newborn infants are major malformations, midface and digit hypoplasia, microcephaly, and growth retardation. Experience has shown the importance of systematic evaluations4 for these outcomes, including definitions of the physical features being looked for, measurements, inclusion and exclusion criteria5 for major malformations, and regular assessments of the reproducibility of the findings.6, 7

Major malformations

Theoretically each anticonvulsant drug could produce specific or distinctive abnormalities; a few have been identified. Five percent of valproic acid exposed infants in one large study8 and 1% of carbamazepine exposed infants9 had spina bifida; nothing distinctive about the spina bifida lesion has been reported and the frequency of other neural tube defects, such as anencephaly, is not increased. Long bone and preaxial deficiencies in valproic acid exposed infants have been reported.10 Stiff, tapered fingers with absent or very small nails in phenytoin exposed infants, in association with …

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