Pituitary-Adrenal Response in Preterm Very Low Birth Weight Infants after Treatment with Antenatal Corticosteroids

Abstract

Antenatal corticosteroids have been widely used for the prevention of respiratory distress syndrome in preterm neonates, yet little is known about their effects on the hypothalamic-pituitary-adrenal axis in these infants. We prospectively evaluated pituitary-adrenal function in 61 preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants on days 7 and 14 of life using the human CRH stimulation test. The baseline and poststimulation plasma ACTH and serum cortisol concentrations did not differ significantly between infants whose mothers received no antenatal corticosteroids, and those whose mothers received 1-2 doses or > 2 doses (mean 7.2 doses) of prenatal dexamethasone (P = > 0.12). The number of doses of dexamethasone and the time intervals between the last dose of drug and delivery did not significantly affect the pituitary-adrenal responsiveness on days 7 and 14 of life. Among infants who did not require mechanical ventilation at the time of the human CRH test, significantly higher plasma ACTH (P < 0.014) and lower serum cortisol concentrations (P < 0.02) were found on day 14 than on day 7. In contrast, none of the poststimulation hormone concentrations were significantly different in ventilated infants between days 7 and 14. The relationship between the blood hormone concentrations in each time epoch (day 7 and day 14) and possible confounding factors including gestational and postconceptional age, birth weight, sex, Apgar scores, mode of delivery, single or higher order births, and mode of ventilation were determined. Plasma ACTH concentrations on day 7 were found to be significantly higher in ventilated than in nonventilated infants (P = 0.006). However, none of the aforementioned factors correlated significantly with plasma ACTH concentrations on day 14. Serum cortisol concentrations on day 7 were significantly higher in infants of greater gestational age (P = 0.039) and birth weight (P = 0.013), with lower Apgar scores at 1 and 5 min (P = 0.021 and P = 0.049, respectively), and in those delivered vaginally (P = 0.047). Similarly, serum cortisol concentrations on day 14 were found to be significantly higher in infants with lower Apgar scores at 1 and 5 min (P = 0.011 and P = 0.014, respectively) and in infants requiring mechanical ventilation (P = 0.014). Our results suggest that single or multiple courses of antenatal dexamethasone have no long-lasting suppressive effects on pituitary-adrenal function in preterm, very low birth weight infants. Maturation of pituitary function appears to be more advanced than adrenal function. The organ's ability to respond appropriately to various stressful stimuli indicates that the pituitary-adrenal axis is highly responsive at these early gestational ages.

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Corticotrophin‐releasing hormone stimulation tests for the infants with relative adrenal insufficiency

“…However, there are no such diagnostic tools available for preterm infants. In preterm infants, there are several reports in which CRH or ACTH stimulation tests were investigated . Yamada reported that secretion of ACTH was decreased in some infants with refractory hypotension, and that pituitary dysfunction may play a role in RAI in preterm infants, at least partly.…”

“…One hundred micrograms of synthetic human CRH (hCRH; Mitsubishi‐Tanabe Pharma, Kyoto, Japan) were diluted using 0.9% NaCl to a final concentration of 5 μg/mL and then administered at a dose of 1 μg/kg via a peripheral intravenous route. The dose of hCRH was selected based on previous studies of premature infants . In the previous studies, cortisol levels peaked at around 30‐min post‐CRH stimulation, thus, blood samples for measuring serum cortisol were collected at 0 and 30 minutes after the administration of hCRH.…”

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“…97-100 Transient alterations of HPA axis function have been found to occur in infants of women who were treated with corticosteroids late in pregnancy. 97,98,[101][102][103][104] Cushing's syndrome with suppression of the HPA axis was reported in one infant whose mother had been treated with 7 courses of betamethasone during pregnancy. 105 In one long-term study, prenatal exposure to a single course of betamethasone late in pregnancy had no clinical effect on cognitive functioning, health-related quality of life, or cardiovascular risk factors in 30-year-old subjects.…”