In utero exposure to steroid contraceptives and survival during infancy

A cohort study was conducted in Chiang Mai, northern Thailand, in 1,431 children of women who had used the injectable contraceptive Depo-Provera (The Upjohn Company, Kalamazoo, Michigan), 565 children of women who had used oral contraceptives during pregnancy, and a group of 2,307 control infants with no hormonal contraceptive exposures. In follow-up interviews, information was obtained on stillbirths and deaths. Cause of death was ascertained by interview, death certificate, or medical record, and underlying causes of death were ascribed by a panel. The children exposed in utero to Depo-Provera had higher neonatal and infant mortality rates (44.3 and 62.9 per 1,000 live births, respectively) than did the controls (19.8 and 29.1 per 1,000 live births). Mortality in infants exposed in utero to oral contraceptives was intermediate between that in the other two groups. Adjustment by logistic regression showed no significantly increased risk of mortality among infants exposed to oral contraceptives, but the odds ratio for death was significantly increased with Depo-Provera exposures due to accidental pregnancy (odds ratio (OR) = 1.8 (95% confidence interval (Cl) 1.1-3.0) for neonatal deaths; OR = 2.0 (95% Cl 1.3-3.2) for infant deaths). Adjustment for low birth weight reduced the risks, suggesting that low birth weight may act as an intermediate determinant of Depo-Provera-associated mortality. Among the accidental pregnancies with Depo-Provera, there was a relation between shorter injection-to-conception intervals, when maternal blood levels of the drug are high, and an increased risk of mortality. The odds ratios for neonatal mortality were 2.5 (95% Cl 1.1-5.7), 2.1 (95% Cl 1.0-4.6), and 0.9 (95% Cl 0.4-2.4) for injection-to-conception intervals of less than or equal to 4, 5-8, and greater than 9 weeks, respectively. Adjustment for low birth weight reduced these risks. Chi-square tests for trend were highly significant. Similar associations were also observed between Depo-Provera accidental pregnancies and risks of low birth weight. Thus, infants from accidental pregnancies that occur 1-2 months after a 150-mg Depo-Provera injection may be at increased risk for low birth weight and death. However, the attributable risk is low, because such pregnancies are uncommon.