Pharmacologic sex hormone use before and in early pregnancy in relation to birth and early childhood anthropometric outcomes

Abstract

Objective: Possible adverse effects resulting from use of hormonal contraceptives have been studied extensively, yet few studies have been conducted evaluating the association between hormonal contraceptive use and offspring anthropometric indices and most studies have been unable to explore formulation-specific effects. Methods: Using data from a large, prospective pregnancy cohort study (n=44,734), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives (defined from dispensed prescription data) prior to and in early pregnancy (characterized by last date of use relative to conception, 12 - >4 months before, 4 - >1 months before, 1 - > 0 months before, and 0-12 weeks after) and preterm birth, small for gestational age, and overweight or obesity at age 3. We characterized use of a hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. Results: We observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (adjusted OR: 1.21, 95% CI: 1.04, 1.41 for exposure within 12 months before conception). Generally, use of other types of hormonal contraception was not associated with preterm birth. Overall, use of a hormonal contraceptive was unrelated to small for gestational age. Evaluation of the association by progestin type identified variation by progestin formulation. We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted OR: 0.75, 95% CI: 0.53, 1.08) and a weak, positive association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). Observed associations were robust to sensitivity analyses. Conclusion: Hormonal contraceptive use prior to and in early pregnancy may be associated with preterm birth and offspring overweight. The association appears contingent upon the specific type or progestin component used. The potential for confounding by indication cannot be ruled out. Larger studies using population-based pregnancy cohort data with linkage to prescription registries may offer the potential to explore these questions further.Doctor of Philosoph

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