OR32-08 Longitudinal Urinary Profiles of Glucocorticoid Precursors and Metabolites During the First Postnatal Year in Preterm Infants Born <30 Weeks of Gestation

Abstract Disclosure: T. Kuiri-Hänninen: None. C.E. Flueck: None. S. Silvennoinen: None. U. Sankilampi: None. Context. The fetal zone of the adrenal cortex remains active in preterm (PT) infants to term equivalent age (TEA), and then involutes. In addition to DHEAS, the main product of the fetal zone, levels of glucocorticoid (GC) precursors are elevated in PT infants while clinical signs of GC deficiency are observed in neonatal intensive care. Maturation of the GC metabolic pathways in PT infants during their first year of life are not well understood. Objective. To describe the temporal and maturational changes in the GC metabolic pathway in PT infants in comparison to full-term (FT) infants during the first year of life. Design and Setting. Urinary samples were collected in PT infants every two weeks from one week of age until discharge from NICU, and thereafter every 1-3 months at follow-up visits. Participants. Sixteen (8 boys) PT infants born <30 weeks of gestational age provided altogether 154 spot urine samples (4-15 samples/child). Data of matched FT infants were available from the same laboratory. Main Outcome Measures. Urinary levels of GC precursor metabolites (5PT, PD, 17-HP, PT and THS), fetal zone metabolite 16α-OH-DHEA, and 13 GC metabolites (cortisol, cortisone, 6βOHF, THF, 5αTHF, THE, α-cortol, β-cortol, α-cortolone, β-cortolone, 20αDHE, 20βDHE and 20αDHF) were quantitated by GC-MS. Enzyme activities in the GC metabolic pathway were evaluated by product/substrate ratios. Mixed models analysis was used for comparisons within and between groups according to both calendar and postmenstrual (PM) age (data were categorized in 8 PM age categories). Results. The levels of GC precursors and 16α-OH-DHEA remained high in PT infants until TEA, after which they decreased (p<0.001). However, GC production, estimated by the sum of 13 GC metabolites (sumGC) did not change significantly over time in PT infants. It was higher in PT than in FT infants after one week of calendar age and in all PM age categories (p= 0.044 - <0.001). The sumGC /THS ratio (representing CYP11B1 activity) increased significantly in PT infants after TEA (p<0.001) while the 16α-OH-DHEA/5PT ratio (representing 17,20-lyase activity) decreased (p<0.001). SRD5A activity, estimated by the 5αTHF/cortisol ratio, was very low in PT infants before TEA and then increased to similar level as in FT infants. The ratio of cortisone metabolites to cortisol metabolites was higher in PT infants before TEA than after it (p<0.001). Conclusions. Postnatal activity of the fetal adrenal zone was associated with high production rate of GC precursors in PT infants. Nevertheless, the total GC production estimated by sumGC remained quite constant and was regulated at the level of CYP11B1 in PT infants. While maturation of GC metabolizing enzyme activities occurred over time, the sumGC remained constantly higher in PT than in FT infants, indicating possible long term programming effects of prematurity on HPA axis. Presentation: Monday, July 14, 2025