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Previous Volume 344:1132-1138 April 12, 2001 Number 15 Next

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ABSTRACT

Background The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known.

Methods We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size.

Results The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants.

Conclusions A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself.

Source Information

From the Genetics and Teratology Unit, Pediatric Service, Massachusetts General Hospital (L.B.H., E.A.H., K.B.H., A.M.H.); the Department of Biostatistics, Harvard School of Public Health (B.A.C., L.M.R.); and the Department of Neurology, Brigham and Women's Hospital (S.K.) — all in Boston.

Address reprint requests to Dr. Holmes at the Genetics and Teratology Unit, Warren 801, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114-2696, or at holmes.lewis{at}mgh.harvard.edu.

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