Oral Contraceptives and Congenital Limb-Reduction Defects

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Abstract
Exposure to exogenous sex steroids during pregnancy was investigated for 108 mothers of patients with congenital limb-reduction defects and 108 mothers of normal controls. Exposure resulted from pregnancy tests, supportive hormone therapy, and breakthrough pregnancies occurring while the mother was using oral contraceptives. Among mothers with malformed children, 15 (14 per cent) had a history of exposure; four (4 per cent) control mothers of normal children were exposed. Of the 15 exposed and affected children, the mothers of 11 had received orally administered hormones. The sex ratio of the nonexposed children was not exceptional, but affected children with a history of exposure to orally administered hormones were all males. This association suggests that orally ingested progestins may have an effect on the developing fetus that is sex-specific. (N Engl J Med 291:697–700, 1974)