The purpose of this proposal is to evaluate the effects of intravenous dexamethasone therapy on pulmonary function and clinical status of infants less than 1,500 gm birthweight who are ventilator dependent and need oxygen supplementation at 3 weeks of age. These infants are at highest risk for the development of bronchopulmonary dysplasia (BPD), the chronic lung disease complicating ventilation and supplemental oxygen therapy in the treatment of respiratory failure. The long-term outcome to infants in the study will be examined at 1, 2, and 3 years of age for evidence of continuing chronic lung disease, cor pulmonale, neurodevelopmental and growth problems. Although steroid therapy of these infants has been reported, there has been no prospective, randomly controlled trial in a large group of infants to determine if this therapeutic intervention should be used in infants who are developing or who have BPD. Currently, BPD is predominantly a complication for infants less than 1,500 gm birth weight who have had respiratory failure and have needed mechanical ventilation and supplemental oxygen therapy for 2 weeks or longer. There continues to be a 25% mortality and significant morbidity in patients who have BPD. This study would potentially include 60 to 90 infants in a randomly controlled, double blind study where either dexamethasone or placebo would be given intravenously for a period of 10 days. Pulmonary function measurements would be made before and after the therapeutic trial. These studies would include measurements of minute ventilation, compliance, pulmonary resistance, work of breathing, alveolar-arterial oxygen and carbon dioxide gradients, physiologic dead space and functional residual capacity. Preliminary reports of pulmonary function studies suggest that pulmonary compliance improves and the work of breathing decreases so that the infant can be weaned from mechanical ventilation and thereby interrupt the lung injury secondary to barotrauma and high oxygen supplementation. If infants 1,500 gm or less at birth can be weaned from mechanical ventilation by 3 weeks of age, the ongoing lung injury and development of BPD with its long-term pulmonary morbidity can be significantly reduced. This study is important because these data will determine if steroids are effective in improving lung function so that the duration of ventilation can be reduced without serious adverse effects. If the steroids prove ineffective, this also would be valuable information since unnecessary steroid therapy can be avoided.
| Ariagno, R L; Fulroth, R; Baldwin, R B et al. (1991) Incidence of bronchopulmonary dysplasia, growth failure, and pulmonary dysfunction assessed by clinical scoring. J Perinatol 11:311-4 |
| Wilson, D M; Baldwin, R B; Ariagno, R L (1988) A randomized, placebo-controlled trial of effects of dexamethasone on hypothalamic-pituitary-adrenal axis in preterm infants. J Pediatr 113:764-8 |
