Intratracheal budesonide with surfactant cuts BPD at 36 weeks, but only when given within 4 hoursMixing budesonide with surfactant may help infants with lung issues

European journal of pediatrics Published October 30, 2026 Study authors: Minamitani Yohei, Saito Kana, Miyahara Naoyuki, Kanai Masayo, Liu Shuxian, Namba Fumihiko, Ota Erika PubMed ↗ DOI ↗ Editorial oversight: Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

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Key Takeaway

Interpret the budesonide-surfactant BPD benefit as timing-dependent and hypothesis-generating.

This meta-analysis pooled 15 trials including 3522 infants to assess intratracheal budesonide mixed with surfactant versus surfactant alone for bronchopulmonary dysplasia. The primary outcome was BPD at 36 weeks' postmenstrual age (BPD36), reported across 14 trials including 3494 infants.

Overall, budesonide with surfactant was associated with a reduction in BPD36 (RR 0.71, 95% CI 0.59-0.86), with substantial heterogeneity (I=68%). The effect differed by timing of treatment. In 8 trials restricted to within 4 hours after birth (1065 infants), BPD36 was reduced (RR 0.58, 95% CI 0.46-0.72). In 4 trials permitting treatment after 4 hours (2011 infants), there was no reduction (RR 0.98, 95% CI 0.91-1.06; P for subgroup difference < 0.00001). The composite of BPD or death showed a similar pattern, though effect estimates were not reported.

The authors list substantial heterogeneity, the post hoc nature of the timing subgroup, potential study-level confounding, and small-study effects as limitations. A GRADE assessment was performed, and the authors describe the restricted-timing finding as hypothesis-generating, possibly reflecting differences between earlier small trials and contemporary large trials. Safety and adverse event data were not reported, and funding or conflicts were not reported.

The authors conclude that current evidence does not support routine budesonide-surfactant therapy. The timing-dependent signal warrants cautious interpretation rather than a change in routine practice.

How this fits prior evidence

Prior coverage has been mixed on early neonatal respiratory and infection outcomes. Early prophylactic hydrocortisone did not reduce BPD or mortality in extremely preterm infants and increased late-onset sepsis risk, while early enteral feeding in VLBW infants reduced sepsis without increasing NEC or mortality. This meta-analysis extends that picture by examining a different strategy, intratracheal budesonide with surfactant, and reports an overall BPD36 reduction (RR 0.71) that is concentrated in trials restricted to within 4 hours after birth (RR 0.58) and absent when later treatment was permitted (RR 0.98). Like the hydrocortisone findings, it argues against assuming that any early anti-inflammatory approach reliably improves BPD outcomes.

When babies are born with serious lung issues, doctors often use a substance called surfactant to help them breathe. Some researchers looked at whether adding a steroid called budesonide to this mixture could improve outcomes for infants at risk of bronchopulmonary dysplasia, a chronic lung condition. They looked at data from over 3,500 infants across 15 different trials.

The results showed a clear difference based on timing. In trials where the mixture was given within four hours of birth, the risk of lung disease dropped significantly. However, in trials where the treatment was given later than four hours, no such benefit was found. This suggests that the timing of the treatment is a critical factor for the medicine to work.

While the data for early treatment is promising, it is still considered a hypothesis-generating finding. This means more research is needed to be certain. Because of differences in how various studies were designed, experts do not currently recommend using budesonide as a routine treatment for all infants. Talk to a medical professional about the best care for a specific infant.

What this means for you:

Adding budesonide to surfactant may help infants with lung issues, but only if given within four hours of birth.

Common questions

Does adding budesonide help infants with lung issues?

Adding budesonide to surfactant may reduce the risk of bronchopulmonary dysplasia in infants. However, this benefit was only seen in trials where the treatment was given within four hours of birth. In trials where treatment was allowed after four hours, no reduction in lung issues was found.

How does the timing of the treatment affect the outcome?

Timing is very important. In a group of 1,065 infants where treatment was given within four hours of birth, the risk of lung disease dropped. In a different group of 2,011 infants where treatment could be given after four hours, there was no change in the risk of lung disease.

Is this a standard treatment for all infants?

No, current evidence does not support using budesonide and surfactant as a routine treatment for all infants. Because the findings for early treatment are still considered hypothesis-generating and may be affected by how different studies were designed, you should consult a doctor for specific medical advice.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedOct 2026

PMID42955434

View Original Abstract ↓

UNLABELLED: The aim of this study was to evaluate whether intratracheal budesonide mixed with surfactant prevents bronchopulmonary dysplasia (BPD) and whether timing contributes to heterogeneity. We searched MEDLINE, Embase, CENTRAL, Web of Science, and trial registries for randomised controlled trials of budesonide-surfactant versus surfactant alone. Random-effects meta-analyses yielded risk ratios (RRs) with 95% confidence intervals (CIs). We assessed risk of bias with RoB 2 and certainty of evidence with GRADE. A post hoc subgroup analysis classified trials by whether treatment was restricted to within 4 h after birth or permitted after 4 h. We included 15 trials (3522 infants); 14 trials (3494 infants) reported BPD at 36 weeks' postmenstrual age (BPD36). The overall analysis suggested a reduction in BPD36 (RR 0.71; 95% CI, 0.59-0.86; I = 68%), although heterogeneity was substantial. BPD36 was reduced in trials restricting treatment to within 4 h (RR 0.58; 95% CI, 0.46-0.72; eight trials; 1065 infants), but not in trials permitting later treatment (RR 0.98; 95% CI, 0.91-1.06; four trials; 2011 infants; P for subgroup difference < 0.00001). The composite outcome of BPD or death showed a similar pattern. Mortality and most other neonatal outcomes did not differ between groups. CONCLUSION: In trials restricting treatment to within 4 h after birth, budesonide-surfactant therapy may reduce BPD36; however, this post hoc, trial-level finding is hypothesis-generating and may reflect differences between earlier small and contemporary large trials. Current evidence does not support routine budesonide-surfactant therapy. A large prospective trial of early administration is needed to determine whether timing modifies benefit. TRIAL REGISTRATION: PROSPERO (CRD42024547670). WHAT IS KNOWN: • Earlier small trials suggested that budesonide mixed with surfactant reduces BPD, whereas recent large multicentre trials found little or no benefit. • The source of the marked heterogeneity among trials remains uncertain. WHAT IS NEW: • Trials restricting treatment to within 4 h showed reductions in BPD36 and BPD or death, whereas trials permitting later treatment showed no benefit. • This post hoc association with timing may reflect study-level confounding and small-study effects and requires confirmation.

Intratracheal budesonide with surfactant cuts BPD at 36 weeks, but only when given within 4 hoursMixing budesonide with surfactant may help infants with lung issues

How this fits prior evidence

Common questions

Study Details

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Intratracheal budesonide with surfactant cuts BPD at 36 weeks, but only when given within 4 hoursMixing budesonide with surfactant may help infants with lung issues

How this fits prior evidence

Common questions

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