Adrenal Steroid Metabolism and Blood Pressure in 5- to 7-Year-Old Children Born Preterm as Compared to Peers Born at Term

Abstract

Background: Previous studies indicated preterm birth to be a risk factor for hypertension in adolescence and adulthood. However, studies in children investigating the underlying mechanisms are scarce. Objective: We hypothesized children born preterm to have higher excretion of cortisol and/or androgen metabolites per day concomitantly with higher blood pressure as compared to peers born at term. We thus aimed to compare urinary steroid profiles and blood pressure between 5- to 7-year-old children born preterm and peers born at term. Furthermore, aldosterone precursor excretion per day was compared between both groups. Methods: Blood pressure was measured in 236 children (preterms n = 116; gestational age 29.8 ± 2.6 (30; 24-33) weeks [mean ± standard deviation (median; range)]) using an automatic oscillometric device. Urinary steroid profiles were determined in 24-h urine samples (preterms n = 109; terms n = 113) using gas chromatographic-mass spectrometric analysis. To assess excretion of cortisol and androgen metabolites per day, major cortisol and androgen metabolites were summed, respectively. To assess aldosterone excretion per day tetrahydrocorticosterone, 5α-tetrahydrocorticosterone, and tetrahydro-11-deydrocorticosterone were summed. Results: Multiple regression analyses showed prematurity to be associated with systolic but not with diastolic blood pressure. When adjusted for potential confounders (prematurity, gender, age at day of examination, being born small for gestational age, breastfeeding, accelerated weight gain during infancy, family history of cardiovascular disease, parental hypertension, and body mass index) prematurity was shown to be associated with an increase in systolic blood pressure by 2.87 mmHg (95% confidence interval 0.48-5.27; p = 0.02). Cortisol, androgen metabolite, and aldosterone precursor excretion per day were not higher in individuals born preterm. In contrast to our hypothesis, multiple regression analysis showed prematurity to independently decrease cortisol and aldosterone precursor excretion per day (p < 0.001 and 0.04, respectively). Conclusion: This study provides further evidence for systolic blood pressure to be higher after preterm birth as early as at the age of 5 to 7 years. However, this seems not to be explained by elevated excretion of cortisol and/or androgen metabolites.

Keywords: adrenal steroid; blood pressure; cortisol; developmental origin of adult disease; prepubertal; preterm; preterm birth; steroid metabolism.