A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: Comparison of early and late treatment and of dexamethasone and inhaled budesonide

Aim. To compare early (<3 days) with late (>15 days) steroid therapy and de xamethasone with inhaled budesonide in very preterm infants at risk of deve loping chronic lung disease. Methods. Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatm ent groups in a factorial design: early (<72 hours) dexamethasone, early bu desonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0. 50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days o f therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 mug/kg twice daily for 12 days. Dela yed selective treatment was started if infants needed mechanical ventilatio n and >30% oxygen for >15 days. The factorial design allowed 2 major compar isons: early versus late treatment and systemic dexamethasone versus inhale d budesonide. The primary outcome was death or oxygen dependency at 36 week s and analysis was on an intention-to-treat basis. Secondary outcome measur es included death or major cerebral abnormality, duration of oxygen treatme nt, and complications of prematurity. Adverse effects were also monitored d aily. Results. There were no significant differences among the groups for the pri mary outcome. Early steroid treatment was associated with a lower primary o utcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18 ) but even after adjustment for confounding variables the difference remain ed nonsignificant. Dexamethasone-treated infants also had a lower primary o utcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remaine d not significant after adjustment. For death before discharge, dexamethaso ne and early treatment had worse outcomes than budesonide and delayed selec tive treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 af ter adjustment, respectively) with the results not quite reaching significa nce. Duration of supplementary oxygen was shorter in the early dexamethason e group (median: 31 days vs 40-44 days). Early dexamethasone was also assoc iated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no dif ference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyp erglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significanc e. Conclusions. Infants given early treatment and dexamethasone therapy had im proved survival without chronic lung disease at 36 weeks compared with thos e given delayed selective treatment and inhaled budesonide, respectively, b ut results for survival to discharge were in the opposite direction; howeve r, none of these findings attained statistical significance. Early dexameth asone treatment reduced the risk of persistent ductus arteriosus. Inhaled b udesonide may be safer than dexamethasone, but there is no clear evidence t hat it is more or less effective.