Several studies have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. We conducted a case-control study of first-trimester sex hormone exposure among mothers of 1,091 infants with Down syndrome or at least one of 11 major malformations. For each malformation category, the infants with other malformations served as the control group. Associations were found between esophageal atresia and (1) any sex hormone exposure (odds ratio, 2.84); (2) progestins (odds ratio, 2.87); (3) nonspecified sex hormones (odds ratio, 2.99); and (4) hormonal pregnancy tests (odds ratio, 2.81). We found no potentially confounding variables for these associations. We found no statistically significant association between any malformation category and oral contraceptive exposure. Even if the relationship between esophageal atresia and noncontraceptive sex hormone exposure is causal, the absolute risk would be low, on the order of six per 10,000 exposed live births.
Lammer EJ, Cordero JF. Exogenous Sex Hormone Exposure and the Risk for Major Malformations. JAMA. 1986;255(22):3128–3132. doi:10.1001/jama.1986.03370220090033
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