Elevation of corticosterone and 17OH progesterone in extremely preterm infants and clinical implications

Abstract

Background: A greater understanding of gestational age-adjusted steroid profiles in preterm neonates is needed to inform diagnosis, optimal timing, dosage, and duration of postnatal steroid therapy for preterm infants with adrenal insufficiency. Therefore, we evaluated changes in steroid profiles using newborn screening dried blood spots (DBS) to determine the impact of prematurity on fetal adrenal function. Methods: Cortisol and its biosynthetic precursors were quantified in 813 anonymized DBS from newborns between 23 to 42 weeks of gestation, collected within 72 hours of birth and again approximately two weeks later. Steroid quantification was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with analyses stratified by gestational and postnatal ages. Results: Extremely preterm infants often had elevated cortisol levels, with a general decline as gestational age increased. Levels of 17-hydroxyprogesterone (17OHP4) and corticosterone were significantly higher in most preterm newborns, with 17OHP4 showing the strongest inverse correlation with gestational age. In contrast, aldosterone levels remained unaffected by gestational age. Conclusions: Elevations in 17OHP4 and corticosterone, rather than cortisol alone, reflect prematurity’s effect on adrenal sufficiency. Preterm infants with high cortisol and elevated corticosterone and 17OHP4 levels may struggle to meet their physiological cortisol needs through the hypothalamic-pituitary-adrenal axis, increasing the risk of adrenal crises. These findings provide important insights to guide the management of adrenal insufficiency in preterm neonates. Impact: The increasing survival of preterm infants born at earlier gestational ages presents clinicians with the complex challenge of distinguishing normal from abnormal adrenal function, a determination which may be critical for survival. Our study advances the understanding of adrenal dysfunction in this population by employing analytical methods rooted in the steroid biosynthesis pathway’s maturation. By utilizing techniques traditionally used to diagnose congenital adrenal hyperplasia (CAH), we provide actionable guidance for interpreting steroid data in preterm infants, offering a practical framework for improved clinical decision-making.