Serum Cortisol, Dehydroepiandrosterone Sulfate, and Steroid-Binding Globulins in Preterm Neonates: Effect of Gestational Age and Dexamethasone Therapy

Abstract

Our aim was to assess adrenocortical function in very low birth weight infants, specifically to evaluate the impact of gestational age and dexamethasone (DEX) therapy on serum concentrations of total and free cortisol, dehydroepiandrosterone sulfate (DHEAS), and steroid-binding globulins. Twelve moderately preterm or full-term neonates of 38 +/- 4 (mean +/- SD) wk of gestation and 36 ill preterm neonates of 26 +/- 2 (mean +/- SD) wk of gestation were studied. Twenty-three of the 36 ill preterm neonates participated in a randomized neonatal DEX trial for the treatment of early chronic lung disease and received a 1-wk treatment of DEX or placebo. Serum concentrations of cortisol, corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), and DHEAS were measured, and an ACTH test was performed. Gestational age correlated with the umbilical cord concentrations of total cortisol (r = 0.702, p < 0.01), free cortisol (r = 0.489, p < 0.05), DHEAS (r = 0.608, p < 0.01), and SHBG (r = 0.831, p < 0.01), but not significantly with the concentration of CBG (r = 0.428, p = 0.076). One-week DEX therapy decreased the serum concentrations of CBG (DEX 295 nmol/L, placebo 504 nmol/L; p < 0.01), DHEAS (DEX 6.5 mumol/L, placebo 11.8 mumol/L; p < 0.05), and the basal (DEX 81 nmol/L, placebo 176 nmol/L; p < 0.01) and ACTH-stimulated cortisol levels (DEX 458 nmol/L, placebo 817 nmol/L; p < 0.05). One week after discontinuation of DEX or placebo, basal cortisol concentrations did not differ significantly, but ACTH-stimulated cortisol levels were lower in the DEX-treated than in the placebo-treated infants. DEX therapy decreased the serum CBG and DHEAS concentrations and caused a transient suppression in the adrenocortical function. Despite severe illness, the very preterm neonates had relatively low basal cortisol concentrations, suggesting their reduced ability to respond adequately to stress during intensive care.

Effect of Single and Multiple Courses of Prenatal Corticosteroids on 17-Hydroxyprogesterone Levels: Implication for Neonatal Screening of Congenital Adrenal Hyperplasia

“…By doing so, we observed a significant difference in blood-spot 17-OHP concentration among groups, whereas other potentially influential variables (gestational age, infectious disease, RDS, and so on) were similar. Several studies of the impact of antenatal corticosteroids on adrenal function, totaling Ͼ200 premature infants, have shown that antenatal therapy decreases blood cortisol and dehydroepiandrosterone sulfate by~50% for 7 d after birth (25,26). Overall, these results suggest that our observation of an impact of antenatal corticosteroid on blood 17-OHP should not be surprising, although this impact was dependent on the cumulative dose and/or the number of courses of betamethasone.…”

“…In view of our results, a moderate level of blood-spot 17-OHP in a premature infant who has received multiple courses of antenatal steroids should be the object of careful interpretation. Because antenatal glucocorticoids may suppress adrenal function for~1 wk after birth (25,26), a second screening test for CAH at 1-2 wk of age could be recommended for these infants. Initially proposed to detect more cases of simple virilizing CAH in term newborns (35), this would be useful for premature infants, provided that salt loss is monitored carefully between the two screenings.…”

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

“…In particular, infants born at lower gestational ages who are sickest commonly show low basal cortisol and adrenal insufficiency (e.g. Hanna et al, 1997;Kari et al, 1996;Ng et al, 2001;Scott and Watterberg, 1995). In addition, preterm infants recovering from chronic lung disease may show decreased cortisol in response to ACTH 3 weeks after birth (Watterberg et al, 2001).…”

Neonatal Screening for Congenital Adrenal Hyperplasia: 17-Hydroxyprogesterone Levels and CYP21 Genotypes in Preterm Infants

“…Several authors reported basal cortisol levels in neonates to be depressed within 6 hours of treatment with dexamethasone or betamethasone and to remain low for 7 days. 26,27 Some studies indicate that extremely preterm and severely ill infants have surprisingly low basal cortisol. The reasons for this have been suggested to be reduced ability to respond adequately to stress, because of either an inability to produce cortisol or an inability to recognize the stress and/or an inappropriate corticotropin-releasing hormone release.…”