Adrenal Function in Sick Very Preterm Infants

Abstract

Some very preterm neonates admitted to the neonatal intensive care unit show circulatory and respiratory problems that improve after administration of steroids. It is unclear whether these symptoms could be caused by adrenal insufficiency. The objective of our study was to investigate the cortisol levels and the cortisol release from the adrenals after ACTH in very preterm infants with and without severe illness and to find whether a relation exists between adrenal function and outcome. An ACTH test (0.5 g) was performed on d 4 in 21 very preterm infants (gestational age, 25.6 -29.6 wk; birth weight, 485-1265 g). Baseline cortisol and 17-hydroxyprogesterone (17OHP) levels and the cortisol levels 30, 60, and 120 min after ACTH administration were measured. The Score for Neonatal Acute Physiology was used to measure illness severity. All infants showed an increase in cortisol levels after ACTH, but the cortisol levels were significantly lower in the ventilated more severely ill infants. After adjusting for birth weight and gestational age, the mean baseline cortisol levels and cortisol/17OHP ratios were significantly lower and the 17OHP levels significantly higher in the ventilated infants compared with the nonventilated infants. Patients with an adverse outcome had significantly lower baseline cortisol/ 17OHP ratios and 60-min cortisol levels during ACTH testing (p ϭ 0.002 and p ϭ 0.03, respectively). These data suggest an insufficient adrenal response to stress in sick ventilated very preterm infants with gestational ages younger than 30 wk compared with nonventilated less sick preterm infants. Further studies are required to investigate whether supplementation with physiologic doses of hydrocortisone may benefit the outcome. With increasing neonatal and obstetric treatment modalities, younger and smaller neonates are admitted to neonatal intensive care units (NICU). Some of these infants show not only respiratory but also circulatory problems such as systemic hypotension resistant to volume expansion and cardiotonic drugs but reactive to the administration of corticosteroids (1). Declining cortisol levels in the first week of life in patients with ongoing respiratory problems are reported (2), and a higher incidence of bronchopulmonary dysplasia (BPD) in patients with an insufficient cortisol response to ACTH has been found (3).In the 1970s, the adrenal function of preterm neonates was investigated after administration of a short course of corticosteroids during gestation, and no signs of adrenal insufficiency were found (4). These preterm neonates, however, were born after a greater gestational age, had a higher birth weight than the infants presently seen in the NICU, and were tested with a relatively high dose of ACTH (15 g/kg) on the first day of life. In infants exposed to long courses of corticosteroids during gestation, no evidence of adrenal insufficiency was found when tested with a higher dose of ACTH (36 g/kg) (5). These infants, however, were of greater gestational age compared with the very preterm...

Relative adrenal insufficiency in the preterm and term infant

“…24,25 Subsequently, numerous studies have described lower cortisol concentrations and/or lower response to ACTH in critically ill preterm infants compared with well infants, in those receiving inotropic support compared with those not, and in those presenting with respiratory distress syndrome compared with those without. [26][27][28][29][30] In addition, several authors have reported lower cortisol responses to ACTH in infants who subsequently develop bronchopulmonary dysplasia. 28,31 -34 The possible relationship between adrenal insufficiency and cardiovascular instability is of particular interest, because if this is true, glucocorticoids may be a more appropriate therapy for hypotension than vasopressors.…”

Maternal stress and behavior modulate relationships between neonatal stress, attention, and basal cortisol at 8 months in preterm infants

“…Most studies examining the HPA function in preterm infants during the neonatal period showed evidence of HPA downregulation, for example, lower basal cortisol levels (e.g., Grunau et al, 2005;Hingre, Gross, Hingre, Mayes, & Richman, 1994;Huysman, Hokken-Koelega, De Ridder, & Sauer, 2000;Lee, Rajagopalan, Berg, & Moshang, 1989;Ng et al, 2004;Watterberg, Gerdes, & Cook, 2001). These lower levels appear to persist to the early infancy period (Haley, Grunau, Weinberg, & Whitfield, 2004;Haley et al, 2006).…”

The use of an early ACTH test to identify hypoadrenalism-related hypotension in low birth weight infants

“…This condition has been labeled 'transient or relative adrenal insufficiency'. 1,[3][4][5][6][7] Transient adrenal insufficiency (TAI) in the first days of life is associated with refractory hypotension, significant respiratory distress, patent ductus arteriosus and bronchopulmonary dysplasia (BPD). 1,5,[8][9][10][11] Of critical concern is that significant hypotension is associated with intraventricular hemorrhage, periventricular leukomalacia, increased mortality and later neurodevelopmental disabilities in preterm infants.…”