Chronic lung disease (CLD) in very premature infants has been associated with mechanical ventilation and relative adrenal insufficiency. This multicenter clinical trial tested whether early corticosteroid therapy or minimal ventilatory management would reduce the risk of CLD or death in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants and reduce the complications of therapy. Newborn infants with birth weights of 501-1000 gm who were mechanically ventilated before 12 hrs were randomized in a 2 x 2 factorial design to receive a 10-day tapering course of stress dose of dexamethasone (initial dose 0.15 mg/kg/d) vs a placebo AND minimal ventilation (target PaCO2 greater than 52 mm Hg) vs routine ventilator management (PaCO2 goal less than 48 mm Hg). The dexamethasone intervention was masked; the ventilator therapy was unmasked. The primary outcome was death or chronic lung disease (CLD, oxygen requirement at 36 wks post-menstrual age); the secondary outcomes included reduced deaths before discharge, reduced oxygen requirement at 28 days, oxygen requirement among survivors, the additive beneficial effects of both active therapies; complications of corticosteroids; other adverse outcomes; etc. The sample size of 1200 was based on an incidence of death or CLD of 0.55 in the placebo/control; a relative reduction of 20 percent in treated groups; 90 percent power; and a two-tailed Type I error of 0.05. The sample size was increased to allow assessment of impact on cerebral palsy.

Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. Neurodevelopment will be assessed by a masked, certified examiners at 18-22 months postmenstrual age.