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

Pediatr Res. 2017 Jan;81(1-1):88-93. doi: 10.1038/pr.2016.179. Epub 2016 Sep 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Angiotensin I / blood
  • Angiotensin I / urine
  • Angiotensin II / blood
  • Angiotensin II / urine
  • Cohort Studies
  • Female
  • Fetal Organ Maturity / drug effects
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Peptide Fragments / blood
  • Peptide Fragments / urine
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Renin / blood
  • Renin / urine
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology


  • Adrenal Cortex Hormones
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Renin
  • angiotensin I (1-7)