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This version published online on July 19, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0870
A more recent version of this article appeared on October 1, 2005
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Submitted on April 20, 2005
Accepted on July 11, 2005

Cortisol production rates in preterm infants in relation to growth and illness: a non invasive prospective study using GC-MS

Matthias Heckmann*, Michaela F. Hartmann, Birgit Kampschulte, Heike Gack, Rolf-Hasso Bödeker, Ludwig Gortner, and Stefan A. Wudy

Dept. of General Pediatrics and Neonatology, Steroid Research Unit, Institute of Medical Statistics, Justus Liebig University, 35385 Giessen, Germany; Dept. of General Pediatrics and Neonatology, University of Saarland, 66421 Homburg/Saar, Germany

* To whom correspondence should be addressed. E-mail: Matthias.Heckmann{at}paediat.med.uni-giessen.de.

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

Objective: To determine cortisol production rates (CPRs) in preterm infants during early life with extreme illness and thereafter during extra-uterine growth and maturation.

Design: Longitudinal observational study.

Setting: University neonatal intensive care unit.

Patients and Methods: 17 well (27.9 ± 1.8wks) and 44 ill (27.3 ± 1.6) preterm infants were classified by the score for neonatal acute physiology (SNAP). Glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry (GC-MS) in 24-h urinary samples. Urine was collected non-invasively using cellulose nappies and extracted by hydraulic press.

Results: Medians of CPRs (µg kg-1d-1mg creatinine-1) in ill (well) preterm infants were at day 1: 35 (40); day 2: 35 (40), day 3: 48 (53); day 5: 47 (41); week 2: 72 (48); week 3: 73 (37); week 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 (SNAP, P = 0.72). A mature adrenal response was found only in 12/44 (27%) of ill preterm infants, who had CPRs higher than the 3fold median of CPRs of well infants. This mature adrenal response was associated with a significantly higher incidence of cerebral bleeding: 9/12 (75%) vs. 8/32 (25%) without such a response, P = 0.003. During growth CPRs of ill (well) preterm infants decreased: month 2: 30 (18); month 3: 18 (22): correlation between weight gain and decrease of CPRs in ill infants between week 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.
Key words: preterm infant • adrenal • cortisol • gas chromatography • mass spectrometry






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