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

Abstract

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.

Conflict of interest statement

Potential Conflicts of Interest: The authors have no conflicts of interest relevant to this article to disclose.

Figures

Figure 1

Relationship between ANCS and RAAS Gray arrows indicate direction of association with the RAAS: dark gray indicates upregulation of Ang II and light gray indicates upregulation of Ang-(1–7).

Figure 2

ANCS and RAAS Stratified by Race 2a: Plasma Ang II/Ang-(1–7) 2b: Plasma Ang-(1–7) *p = 0.002, **p<0.001. ANCS = dark gray; No ANCS = light gray. Bar denotes median, circle denotes mean, box indicates IQR, and whiskers include ≤1.5x IQR. Between-group comparisons by Wilcoxon Rank-Sum test.

Figure 3

Study Participant Flow Diagram