Conducted across 17 centers in the United States Neonatal Research Network, the trial enrolled 641 infants born between 22 and 28 weeks of gestation or weighing 401 to 1000 grams at birth. The study aimed to determine whether early intratracheal administration of budesonide (0.25 mg/kg) combined with surfactant could lower the incidence of physiologic BPD or death by 36 weeks’ postmenstrual age, compared with surfactant alone.
The infants were randomly assigned in a 1:1 ratio to receive either budesonide plus surfactant (poractant alfa) or surfactant alone, delivered via endotracheal tube within 50 hours of birth. However, the trial was stopped early after reaching a prespecified futility threshold during an interim analysis, meaning further recruitment was unlikely to alter the outcome.
The study revealed the following findings:
- No significant difference was observed between the two groups in the primary outcome of bronchopulmonary dysplasia (BPD) or death.
- The incidence of BPD or death was 68.5% in the budesonide-plus-surfactant group and 67.9% in the surfactant-alone group (adjusted relative risk [RR], 1.00).
- Mortality rates were comparable between groups—15.3% in the budesonide-plus-surfactant group and 13.2% in the surfactant-alone group (adjusted RR, 1.13).
- Among survivors, the rate of BPD by 36 weeks’ postmenstrual age was nearly identical—62.9% in the budesonide group and 63.0% in the control group (adjusted RR, 0.99).
- Hyperglycemia was more frequent in infants who received budesonide with surfactant (66.7%) compared with those given surfactant alone (49.8%).
- The higher incidence of hyperglycemia in the budesonide group raised potential safety concerns regarding systemic steroid exposure in extremely preterm infants.
The investigators concluded that adding budesonide to surfactant offered no additional benefit in reducing the risk of BPD or death among extremely preterm infants. The findings contrast with earlier, smaller trials, which had suggested that this combination therapy might improve outcomes.
However, the study had some limitations. Early termination meant the final sample size was smaller than initially planned, which could have reduced the statistical power to detect modest effects or perform detailed subgroup analyses. Moreover, the findings may be most applicable to populations similar to those in the study—infants with high exposure to antenatal steroids, frequent cesarean delivery, and maternal hypertension.
Despite these constraints, the BiB trial represents the largest and most rigorous assessment to date of budesonide-surfactant therapy in extremely preterm infants. According to the authors, further research may be needed to explore whether different dosing regimens, timing of administration, or alternative corticosteroids could offer benefits without increasing adverse effects.
Reference:
Ambalavanan N, Carlo WA, Nowak KJ, et al. Early Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial. JAMA. Published online September 30, 2025. doi:10.1001/jama.2025.16450
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