Persistent high activity of the fetal adrenal cortex in preterm infants: is there a clinical significance?

BACKGROUND: In preterm infants, the activity of the fetal adrenal cortex continues until term. Dehydroepiandrosterone sulphate can block the synthesis of surfactant in vitro. The incidence of pulmonary disease is higher in male than in female preterm infants. OBJECTIVE: To investigate the relationship between urinary excretion of fetal zone steroids (3beta-OH-5-ene-steroids) and the severity of lung disease in preterm infants with respect to gender. PATIENTS AND METHODS: 3beta-OH-5-ene-steroids were profiled by gas chromatography-mass spectrometry in 24-h urinary samples in 61 preterm infants of less than 30 weeks gestational age. RESULTS: The incidence of respiratory distress syndrome treated with surfactant in females (n = 30) was 47% and in males (n = 31) 71%, p = 0.07. Medians of total excretion rates of fetal zone steroids (microg/kg/d) in female (male) preterm infants were at day 1: 1,317 (895); day 2: 3,154 (7,723), p = 0.03; day 3: 5,502 (9,494), p = 0.08; day 5: 7,140 (10,407); week 2: 8,731 (9,720); week 3: 8,571 (10,079); week 4: 7,620 (7,825). Regression analysis did not reveal a significant influence of maximum excretion rates of fetal zone steroids or gender on the incidence of respiratory distress syndrome treated with surfactant. CONCLUSIONS: Excretion rates of fetal zone steroids were 4-fold higher than previously reported indicating a persistent high activity of the fetal adrenal zone in preterm infants. Excretion rates of fetal zone steroids were significantly higher in male preterm infants compared to females at day 2 (trend at day 3) but did not have a significant influence on the incidence of respiratory distress syndrome.

Cortisol production rates in preterm infants in relation to growth and illness: a noninvasive prospective study using gas chromatography-mass spectrometry.

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 (microg kg(-1) d(-1) mg 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.

Assessing cortisol production in preterm infants: do not dispose of the nappies.

The aim of this study was to develop a practical approach allowing a reliable and noninvasive assessment of cortisol production rates in premature infants. To measure daily urinary excretion rates of glucocorticoids, we developed a procedure using a hydraulic compression method to collect urine from cellulose nappies (diapers). Glucocorticoid metabolites were profiled by quantitative gas chromatography-mass spectrometry. Recovery of steroids after the process of hydraulic extraction from the nappy was approximately 100%. Consecutively, urinary excretion rates of glucocorticoids could be determined in nine healthy preterm infants. The median urinary excretion rate of glucocorticoids increased significantly during the first 5 d of life and remained between 566 microg/kg/d at d 5 and 302 microg/kg/d at 4 wk of age. However, this increase of urinary excretion rates of glucocorticoids in the first days of life was no longer significant when corrected for creatinine excretion. When calculated per square meter body surface area, the median urinary excretion rates of glucocorticoids were 5.1, 4.2, 4.1, and 3.7 mg/m2/d on d 5, and at wk, 2, 3, and 4, respectively. Urinary excretion rates of glucocorticoids constitute approximately 70% of the natural cortisol production rate as determined by stable isotope dilution technique in older children. Additionally, low cortisol production was detected in two of five preterm infants with arterial hypotension requiring treatment with catecholamines. In conclusion, 24-h urine collection using disposable nappies in combination with gas chromatography-mass spectrometry steroid profiling proved to be a reliable, noninvasive, nonstressful procedure to assess cortisol production and metabolism in premature infants.