Glucocorticoid trajectories in preterm infants—born too soon, wired differently

CONTEXT: Levels of glucocorticoid (GC) precursors are elevated in preterm infants, whereas clinical signs of GC deficiency are frequently observed in neonatal intensive care units. OBJECTIVE: To describe the maturation of the GC metabolic pathway in preterm infants during the first year of life. DESIGN AND SETTING: Spot urinary samples (n = 154) were collected in the neonatal intensive care unit and at follow-up visits. PARTICIPANTS: Sixteen preterm infants (8 boys) born <30 weeks of gestational age. Data of full-term infants were available from the same laboratory. MAIN OUTCOME MEASURES: Urinary levels of GC precursor metabolites and 13 GC metabolites were quantitated by gas chromatography-mass spectrometry. Enzyme activities were calculated by product/substrate ratios. Mixed models were used for statistical analyses. RESULTS: The levels of GC precursors remained high in preterm infants until term-equivalent age (TEA), after which they decreased (P < .001). However, GC production, estimated by the sum of 13 GC metabolites did not change significantly over time in preterm infants and was higher in preterm than in full-term infants after 1 week of age (P = .044 -<.001). The sum of 13 GC metabolites/tetrahydro-11-deoxycortisol ratio (representing CYP11B1 activity) increased in preterm infants after TEA (P < .001), whereas the 16α-OH-DHEA/5-PT ratio (representing 17,20-lyase activity) decreased (P < .001). The ratio of cortisone metabolites to cortisol metabolites was higher in preterm infants before TEA than thereafter (P < .001). CONCLUSION: Despite a high production rate of GC precursors in preterm infants, the total GC production remained relatively constant and was regulated at the level of CYP11B1. Persisting differences between preterm and full-term infants in GC precursor levels as well as in GC production were observed, indicating possible programming effects of preterm birth.