Abstract 1328
Clinical Trials in Perinatal Neonatal Medicine Platform, Tuesday, 5/4
We conducted a multicenter randomized double blinded controlled trial comparing early postnatal dexamethasone to selective late dexamethasone therapy in premature infants at 42 centers in the Vermont Oxford Network. Methods: Infants weighing 501-1000 grams were eligible for enrollment at 12 hours of age if they required assisted ventilation, had received surfactant replacement therapy, were physiologically stable, had no obvious life-threatening congenital anomaly, had blood cultures obtained and antibiotic therapy initiated. Infants were randomly assigned to early dexamethasone therapy or saline placebo. Intravenous dexamethasone was administered for 12 days according to the following dosing schedule: 0.5 mg/kg/day for three days, 0.25 mg/kg/day for three days, 0.10 mg/kg/day for three days, 0.05 mg/kg/day for three days. Infants in either group could receive treatment with late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30%. The primary outcome measure was chronic lung disease or death at 36 weeks adjusted age. Results: The study was stopped prior to completion of sample size goals due to concern regarding adverse effects in the early steroid therapy group. 542 infants were enrolled (early therapy n=272, selective therapy n=270). The two groups had similar demographic characteristics. No differences were noted in the primary outcome of chronic lung disease or death at 36 weeks adjusted age (early therapy 50% vs. late therapy 53%, relative risk 0.93, 95% CI 0.79, 1.10). Infants who received early steroid therapy were less likely to receive late steroid therapy (relative risk 0.69, 95% CI 0.59, 0.82); had a lower risk of patent ductus arteriosus (relative risk 0.78, 95% CI 0.63, 0.97); and were less likely to receive indomethacin therapy (relative risk 0.74, 95% CI 0.63, 0.85). However, infants who received early steroid therapy were more likely to have complications associated with therapy including gastrointestinal hemorrhage (relative risk 1.77, 95% CI 1.02, 3.07), hyperglycemia (relative risk 1.29, 95% CI 1.14, 1.46), and use of insulin therapy (relative risk 1.62, 95%CI 1.36, 1.94). Trends toward increased gastrointestinal perforation (relative risk 1.65, 95% CI 0.95, 2.89) and increased systolic blood pressure (relative risk 1.35, 95% CI 0.97, 1.86) were noted. In infants receiving cranial ultrasound examinations, an increase in periventricular leukomalacia was noted in the early steroid therapy group (relative risk 2.25, 95%CI 1.00,5.08). Infants who received early steroid therapy had fewer days in supplemental oxygen, but experienced poor weight gain. Conclusion: A 12 day course of early postnatal dexamethasone therapy given to extremely low birth weight infants did not decrease the risk of chronic lung disease or death at 36 weeks adjusted age and was associated with serious complications and poor weight gain.
