Antenatal corticosteroids and the renin-angiotensin-aldosterone system in adolescents born preterm

Background: Antenatal corticosteroid (ANCS) treatment hastens fetal lung maturity and improves survival of premature infants, but the long-term effects of ANCS are not well-described. Animal models suggest that ANCS increases the risk of cardiovascular disease through programmed changes in the renin-angiotensin (Ang)-aldosterone system (RAAS). We hypothesized that ANCS exposure alters the RAAS in adolescents born prematurely. Methods: A cohort of 173 adolescents born prematurely was evaluated, of whom 92 were exposed to ANCS. We measured plasma and urine Ang II and Ang-(1–7) and calculated Ang II/Ang-(1–7) ratios. We used general linear regression models to estimate the difference in the RAAS between the ANCS-exposed and unexposed groups, adjusting for confounding variables. Results: In unadjusted analyses, and after adjustment for sex, race, and maternal hypertension, ANCS exposure was associated with increased urinary Ang II/Ang-(1–7) (estimate 0.27 (95% CI 0.03, 0.5), P = 0.03), increased plasma Ang-(1–7) (0.66 (0.26, 1.07), P = 0.002), and decreased plasma Ang II/Ang-(1–7) (−0.48 (−0.91, −0.06), P = 0.03). Conclusion: These alterations indicate an imbalance in the urinary RAAS, promoting the actions of Ang II at the expense of Ang-(1–7), which over time may increase the risk of renal inflammation and fibrosis and ultimately hypertension and renal disease.