Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life

Background: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. Objectives: To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. Design and methods: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses. Results: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (beta: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (beta: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (beta: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (beta: 0.932, 95% CI: 0.022 1.843). Conclusions: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.