- Design
- Systematic review and meta-analysis of 15 RCTs
- Population
- 3,522 preterm infants receiving surfactant
- Primary outcome
- BPD at 36 weeks' postmenstrual age
- Effect
- Overall RR 0.71 (0.59–0.86); within 4 h RR 0.58 (0.46–0.72); later RR 0.98 (0.91–1.06)
A systematic review and meta-analysis pooled 15 randomised trials (3,522 preterm infants) comparing intratracheal budesonide mixed with surfactant against surfactant alone.
Overall, bronchopulmonary dysplasia at 36 weeks was reduced (RR 0.71), but heterogeneity was substantial. In a post hoc subgroup, trials restricting treatment to the first four hours showed a reduction (RR 0.58, eight trials, 1,065 infants), while trials allowing later treatment showed none (RR 0.98, four trials, 2,011 infants). Mortality did not differ.
The authors caution that the early trials were small and the later ones large, so timing may be a proxy for trial size and quality. Their conclusion is that routine use is not supported, pending a large trial of early administration.
- Do not use budesonide mixed with surfactant routinely to prevent BPD outside a trial.
- Be aware that apparent benefit is limited to early administration in smaller trials.
- Continue established BPD prevention measures, including non-invasive support and caffeine where indicated.
Why it matters
It explains why small early trials and large recent ones disagreed, without settling it.
Don't overread it
The timing finding is a post hoc subgroup and may reflect small-study effects rather than a true timing effect.
The statistics, in plain English
The subgroup difference is highly significant, but it is between groups of trials, not infants, and those groups differ in many ways. That is why it is hypothesis-generating.
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