Intratracheal budesonide combined with surfactant for respiratory distress syndrome in preterm infants: A randomized clinical trial

Background Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity among preterm infants with respiratory distress syndrome (RDS). Intratracheal budesonide combined with surfactant may reduce pulmonary inflammation and improve neonatal outcomes. Methods In this randomized clinical trial, 160 preterm infants (gestational age 26–32 weeks; birth weight <1500 g) requiring surfactant therapy for RDS were assigned to receive either surfactant alone (n = 80) or surfactant plus budesonide (0.25 mg/kg; n = 80). Primary outcomes were oxygen dependency or respiratory support beyond 21 days of life (the prespecified study respiratory outcome) and in-hospital mortality. Secondary outcomes included sepsis, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, respiratory support duration, and repeat surfactant administration. Results Baseline characteristics were comparable between groups. The primary respiratory outcome occurred in 16/80 infants (20.0%) in the budesonide-surfactant group and 26/80 infants (32.5%) in the surfactant-alone group (absolute risk difference −12.5 percentage points; P = 0.105). Mortality was significantly lower in the combination group (1.2% vs 11.2%, P = 0.018), as was culture-proven sepsis (5.0% vs 21.2%, P = 0.004). Infants receiving budesonide required fewer repeat surfactant doses (38.8% vs 61.3%, P = 0.016) and had a shorter duration of nasal continuous positive airway pressure support (10.1 ± 6.0 vs 17.9 ± 11.3 days, P = 0.001). The composite outcome of death or oxygen dependency/respiratory support beyond 21 days of life occurred in 35 infants (43.8%) in the control group and 17 infants (21.3%) in the combination group ( P = 0.003). Conclusions In preterm infants with RDS, budesonide-surfactant therapy was associated with reduced mortality, sepsis, respiratory support duration, and repeat surfactant use. Although fewer infants in the intervention group met the prespecified respiratory outcome, the difference was not statistically significant. Larger multicenter trials using contemporary BPD definitions and incorporating long-term neurodevelopmental follow-up are needed before efficacy and safety can be established.