TOPLINE:

Intratracheal administration of budesonide mixed with surfactant did not reduce the rates of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely premature infants by 36 weeks of postmenstrual age.

METHODOLOGY:

• In this multicenter randomized clinical trial, investigators assessed whether intratracheal administration of budesonide with surfactant vs surfactant alone lowered the rate of physiologic BPD or death in 641 extremely premature infants (50.1% boys; mean birth weight, 810 g; mean gestational age, 25.9 weeks).
• Infants were randomly assigned to receive either budesonide 0.25 mg/kg or 1 mL/kg mixed with surfactant 2.5 mL/kg (n = 323) or surfactant alone (n = 318), administered via an endotracheal tube within 50 hours after birth.
• The primary outcome was a composite of physiologic BPD or death by 36 weeks of postmenstrual age; physiologic BPD was defined as the need for mechanical ventilation, continuous positive airway pressure, or supplemental oxygen with a fraction of inspired oxygen exceeding 0.30.
• The secondary outcomes were death or physiologic BPD, assessment of BPD severity, including grade 3 BPD, and the use of postnatal steroids from 7 days after the final study dose until 36 weeks of postmenstrual age.

TAKEAWAY:

• The composite outcome of physiologic BPD or death was similar between the budesonide plus surfactant group and the surfactant-alone group (68.5% vs 67.9%; adjusted relative risk, 1.00; 95% CI, 0.90-1.11).
• The treatment groups showed no meaningful differences in the secondary endpoints such as death or physiologic BPD, grade 3 BPD, overall BPD severity, and the use of postnatal steroids.
• The budesonide plus surfactant group experienced more adverse events than the surfactant-alone group, primarily due to increased moderate hyperglycemia, whereas both groups showed no difference in serious adverse events.

IN PRACTICE:

“The key novel contribution of the current trial is that administration of the study intervention with the first dose of surfactant more closely parallels the way budesonide would be used in real-world practice, in contrast to the [prior] multinational trial, where 57% of infants had received prior surfactant,” the investigators of the study wrote.

SOURCE:

The study was led by Namasivayam Ambalavanan, MD, University of Alabama at Birmingham. It was published online on September 30, 2025, in JAMA.

LIMITATIONS:

Terminating the trial early resulted in a smaller-than-intended sample size, reducing statistical power for secondary outcomes and subgroup analyses. The findings may be generalizable only to extremely premature infants with characteristics similar to those of the study population.

DISCLOSURES:

The study was supported by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Center for Advancing Translational Sciences. Some authors disclosed serving as employees, members of data and safety monitoring boards, and medical advisors for; owning stocks of; or receiving grants from various organizations and pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.