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

Levels of glucocorticoid (GC) precursors are elevated in preterm infants, whereas clinical signs of GC deficiency are frequently observed in neonatal intensive care units.

To describe the maturation of the GC metabolic pathway in preterm infants during the first year of life.

Spot urinary samples (n = 154) were collected in the neonatal intensive care unit and at follow-up visits.

Sixteen preterm infants (8 boys) born <30 weeks of gestational age. Data of full-term infants were available from the same laboratory.

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.

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).

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.