Timing of intratracheal administration of budesonide mixed with surfactant to prevent bronchopulmonary dysplasia: a systematic review and meta-analysis.
Yohei Minamitani, Kana Saito, Naoyuki Miyahara et al.
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In 30 seconds
This systematic review and meta-analysis examined randomised trials comparing intratracheal budesonide mixed with surfactant against surfactant alone in infants, assessing bronchopulmonary dysplasia (BPD) and whether treatment timing explained differences between trials. Across 14 trials reporting BPD at 36 weeks’ postmenstrual age (BPD36), the overall estimate suggested lower risk with combination therapy (RR 0.71; 95% CI, 0.59-0.86), with substantial heterogeneity. In a post hoc subgroup analysis, benefit was seen in trials restricting treatment to within 4 h after birth, but not in trials permitting later treatment. The authors consider this finding hypothesis-generating and do not support routine use.
Key findings
- Overall, BPD36 was lower with budesonide-surfactant than surfactant alone (RR 0.71; 95% CI, 0.59-0.86; I 2 = 68%).
- In trials restricting treatment to within 4 h, BPD36 was reduced (RR 0.58; 95% CI, 0.46-0.72; eight trials; 1065 infants).
- Trials permitting treatment after 4 h showed no BPD36 benefit (RR 0.98; 95% CI, 0.91-1.06; four trials; 2011 infants; P for subgroup difference < 0.00001).
- Mortality and most other neonatal outcomes did not differ between groups; BPD or death showed a timing pattern similar to BPD36.
Why it matters
The pooled estimate suggests a possible reduction in BPD, but substantial heterogeneity and the contrasting timing subgroups make the overall result difficult to interpret. The apparent advantage of treatment within 4 h could reflect differences between trials rather than a true timing effect. Distinguishing these possibilities matters before this intervention is incorporated into routine neonatal care.
What to keep in mind
The timing analysis was post hoc and trial-level, so study differences and small-study effects may confound the apparent association. Heterogeneity in the overall analysis was substantial.