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Cortisol Production Rates in Preterm Infants in Relation to Growth and Illness: A Noninvasive Prospective Study Using Gas Chromatography-Mass Spectrometry

Department of General Pediatrics and Neonatology (M.H., B.K., H.G., S.A.W.), Steroid Research Unit (M.F.H., S.A.W.), and Institute of Medical Statistics (R.-H.B.), Justus Liebig University, 35385 Giessen, Germany; and Department of General Pediatrics and Neonatology (L.G.), University of Saarland, 66421 Homburg/Saar, Germany

Address all correspondence and requests for reprints to: Matthias Heckmann, M.D., Department of General Pediatrics and Neonatology, Justus Liebig University, 35385 Giessen, Germany. E-mail: Matthias.Heckmann{at}paediat.med.uni-giessen.de.

Context: Whereas intrauterine growth and maturation depend on low cortisol levels, an adrenal stress response postnatally is thought to be mandatory in preterm infants.

Objective: The goal of this study was to determine cortisol production rates (CPRs) in preterm infants during early life with extreme illness and, thereafter, during extrauterine growth and maturation.

Design: We describe a longitudinal observational study.

Setting: The study was conducted at a university neonatal intensive care unit.

Patients and Methods: Seventeen well (27.9 ± 1.8 wk) and 44 ill (27.3 ± 1.6 wk) preterm infants were classified by the Score for Neonatal Acute Physiology. Glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urinary samples. Urine was collected noninvasively using cellulose nappies and extracted by hydraulic press.

Results: Medians of CPRs (µg kg^–1d^–1mg creatinine) in ill (well) preterm infants were as follows: at d 1, 35 (40); d 2, 35 (40); d 3, 48 (53); d 5, 47 (41); wk 2, 72 (48); wk 3, 73 (37); wk 4, 54 (26). Regression analysis revealed a significant inverse influence of gestational age (P < 0.005) on the maximum of CPRs but not of severity of illness (Score for Neonatal Acute Physiology; P = 0.72). A mature adrenal response was found in only 12 of 44 (27%) ill preterm infants, who had CPRs higher than the 3-fold median of CPRs of well infants. This mature adrenal response was associated with a significantly higher incidence of cerebral bleeding: 9 of 12 (75%) vs. 8 of 32 (25%) without such a response (P = 0.003). During growth, CPRs of ill (well) preterm infants decreased: at month 2, 30 (18); month 3, 18 (22); correlation between weight gain and decrease of CPRs in ill infants between wk 4 and month 3, r = –0.48 (P = 0.027).

Conclusions: Severity of illness did not have a significant influence on CPRs in preterm infants. However, the highest CPRs were associated with a significantly higher incidence of cerebral bleeding. During growth, CPRs decreased significantly, suggesting that preterm infants have the ability to regulate cortisol production. CPRs in ill preterm infants might reflect inadequate stress reaction, but this could also reveal persistence of fetal protective mechanisms against high catabolic cortisol concentrations.

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