Efficacy of pulmonary surfactant with budesonide in infants born at or less than 28 weeks’ gestation: a systematic review and meta-analysis

Pulmonary surfactant (PS) is the standard treatment for respiratory distress syndrome in preterm infants. Budesonide, a corticosteroid with anti-inflammatory properties, has been studied for use with PS to potentially improve respiratory outcomes and reduce bronchopulmonary dysplasia (BPD) risk while minimizing systemic steroid exposure. This study aimed to compare the efficacy of PS with budesonide versus PS alone in infants born ≤ 28 weeks' gestational age (GA). A systematic review and meta-analysis was conducted by searching PubMed, Scopus, Embase, and the Cochrane Library databases from inception to October 21, 2025. Inclusion was restricted to randomized controlled trials (RCTs) examining PS with budesonide efficacy in extremely preterm populations. Risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was assessed with GRADE methodology. The primary outcomes were the incidence and severity of BPD; secondary outcomes included other respiratory measures, pre-discharge mortality, hospital stay duration, and complications related to prematurity. Compared to PS alone, PS with budesonide did not significantly reduce BPD incidence (RR, 0.96; 95% CI, 0.86 to 1.08; p = 0.51; I² = 40%; low-certainty evidence), duration of mechanical ventilation (MD, - 0.45 days; 95% CI, - 2.26 to 1.36; p = 0.62; I² = 0%; moderate-certainty evidence), pre-discharge mortality (RR, 0.92; 95% CI, 0.76 to 1.13; p = 0.44; I² = 0%; low-certainty evidence), or duration of of hospitalization (MD, 0.27 days; 95% CI, - 3.29 to 3.84; p = 0.88; I² = 0%; moderate-certainty evidence). PS with budesonide probably has little or no effect on BPD, respiratory outcomes, other prematurity-related outcomes, or pre-discharge mortality compared to surfactant alone. Most outcomes are based on low- to moderate-certainty evidence. Therefore, current evidence is insufficient to support the superior efficacy of pulmonary surfactant with budesonide over surfactant alone in extremely preterm infants.