Budesonide and Surfactant Therapy Versus Surfactant Alone on Incidence of Lung Disease in Preterm Infants (BEST Lung): Study Protocol for a Systematic Review and Individual Participant Data Meta-Analysis With Nested Prospective Meta-Analysis.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a leading cause of morbidity and mortality in preterm infants. Combining surfactant with budesonide has been proposed to prevent BPD, but results from existing randomised controlled trials (RCTs) are conflicting. Individual participant data meta-analysis (IPD-MA) synthesises raw trial data, increasing precision, improving assessment of data quality and enabling subgroup analyses. This IPD-MA aims to examine the effect of surfactant plus budesonide versus surfactant alone.

METHODS: We will systematically search medical databases and trial registers for RCTs enrolling preterm infants born at < 32 weeks' gestation randomised to intratracheal surfactant alone or surfactant plus budesonide. Studies with major quality concerns will be excluded. Risk of bias will be assessed using Cochrane's RoB 2 tool. Two-stage fixed-effects IPD-MA will be performed with co-primary outcomes of all-cause mortality at hospital discharge and BPD at 36 weeks' postmenstrual age. Subgroups will be examined using treatment-covariate interactions. Certainty of evidence will be assessed using GRADE. A nested prospective meta-analysis will also be conducted. The study is preregistered on PROSPERO (CRD42023456941).

CONCLUSION: If effective, surfactant plus corticosteroid would be a low-cost addition to standard care to reduce BPD and increase survival. IPD-MA will allow further insight into treatment effects.