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Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids
1Department of Pediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong.
Insights
Antenatal corticosteroids, like dexamethasone, do not appear to suppress the hypothalamic-pituitary-adrenal axis in preterm infants. This suggests the axis remains responsive despite prenatal steroid exposure and prematurity.
Area of Science:
- Neonatal endocrinology
- Pediatric critical care
- Reproductive medicine
Background:
- Antenatal corticosteroids are standard for preventing respiratory distress syndrome in preterm neonates.
- Limited data exists on their impact on the hypothalamic-pituitary-adrenal (HPA) axis in these vulnerable infants.
Purpose of the Study:
- To prospectively evaluate the pituitary-adrenal function in preterm infants exposed to antenatal corticosteroids.
- To determine if prenatal dexamethasone affects HPA axis responsiveness in very low birth weight neonates.
Main Methods:
- A prospective study involving 61 preterm infants (<32 weeks gestation, <1500g birth weight).
- Human corticotropin-releasing hormone (CRH) stimulation tests were performed on days 7 and 14 of life.
- Plasma ACTH and serum cortisol levels were measured at baseline and post-stimulation.
Main Results:
- No significant differences in pituitary-adrenal function were observed between infants based on maternal antenatal corticosteroid exposure (none, 1-2 doses, >2 doses).
- Ventilation status impacted HPA axis response: non-ventilated infants showed increased ACTH and decreased cortisol from day 7 to 14, unlike ventilated infants.
- Higher gestational age, birth weight, lower Apgar scores, and vaginal delivery were associated with higher serum cortisol levels on day 7.
Conclusions:
- Prenatal dexamethasone exposure, even multiple courses, does not seem to cause long-term suppression of the HPA axis in preterm, very low birth weight infants.
- Pituitary maturation appears to precede adrenal maturation in this cohort.
- The HPA axis demonstrates high responsiveness to stimuli in early neonatal life, indicating functional resilience.
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.