Reproductive outcomes after antenatal corticosteroids: Secondary analysis of 50-year follow-up of the Auckland steroid randomized trial.

Abstract

Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data. This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation). Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term. Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.