Effect of Dexamethasone Therapy on the Neonatal Ductus Arteriosus

Abstract

Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n = 13) or placebo (n = 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p = 0.05, odds ratio 0.21, 95% confidence interval 0.04-1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p = 0.025, odds ratio 0.08, 95% confidence interval 0.01-0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.

Prophylaxis Against Early Adrenal Insufficiency to Prevent Chronic Lung Disease in Premature Infants

“…Experimentally induced adrenal insufficiency results in greatly amplified inflammation in animal models, with parallels in human disease. 39 -41 Although we postulated that correction of such a deficiency would decrease inflammatory lung injury, the beneficial effects of hydrocortisone seen in this trial may well have resulted from glucocorticoid effects on other organ systems, such as cardiovascular, [42][43][44] intestinal, 33 or renal. 45,46 Many clinical trials of dexamethasone to treat or prevent CLD in premature infants have now been reported, commonly employing a dose of dexamethasone (.5 mg/kg/day) equivalent to 10 to 15 times the dose of hydrocortisone used in this study.…”

Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

“…The causes may range from respiratory distress brought on by diminished lung function to apneic episodes of known or unknown etiology (24,26,31,32). Increased adrenal glucocorticoid production in response to hypoxemia serves a number of adaptive roles, such as augmenting vasoconstrictor responses to circulating catecholamines and promoting lung maturation (11,33). A maximal adrenal response to hypoxemia is often lacking in these patients, necessitating frequent administration of steroids such as dexamethasone and hydrocortisone (66 -68).…”

“…A coordinated hypothalamic-pituitary-adrenal (HPA) axis response may confer a variety of protective mechanisms aimed at coping with brief periods of severe hypoxia. For example, hypoxia-induced increases in plasma glucocorticoids may facilitate the closing of the ductus arteriosus, improve vasoconstrictor responses to circulating catecholamines, and promote maturation of the immature lung (11,33,67). Although acute hypoxia-induced increases in plasma corticosterone have been reported in neonatal rats (62,64), a complete understanding of the development, timing, and mechanisms of the HPA axis response to this stimulus has not been elucidated.…”

Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent corticosterone production during hypoxia

“…It is known that the neonatal response to acute hypoxia involves the hypothalamic-pituitary-adrenal (HPA) axis, resulting in an increase in plasma glucocorticoids that promotes lung maturation and improves the vasoconstrictor response to circulating catecholamines (Morales et al 1998;Watterberg et al 1999;Deruelle et al 2003). The rat adrenal zona fasciculata/reticularis produces the glucocorticoid corticosterone through a well-documented ACTH-dependent cAMP-stimulated pathway (Gallo-Payet and Payet 2003).…”