Berlin, Germany – A recent clinical trial has cast doubt on the effectiveness of early intratracheal budesonide, a corticosteroid, in preventing bronchopulmonary dysplasia (BPD) in extremely preterm infants. The Budesonide in Babies (BiB) Randomized Clinical Trial, halted early due to a lack of positive results, found no significant difference in rates of BPD or death between infants receiving budesonide with surfactant and those receiving surfactant alone. This finding adds to a growing body of research questioning the widespread use of steroids in this vulnerable population.
Bronchopulmonary dysplasia is a chronic lung disease that affects premature babies, often requiring long-term oxygen support and impacting their quality of life. Extremely preterm infants – those born between 22 and 28 weeks gestation – are particularly susceptible. The condition arises from lung injury caused by mechanical ventilation, oxygen therapy, and inflammation. Finding effective preventative measures is therefore a critical area of neonatal research. The BiB trial, conducted across 17 centers within the United States Neonatal Research Network, aimed to determine if early administration of budesonide could mitigate this risk.
Trial Details and Unexpected Results
The BiB trial, which ran from April 2021 to June 2024, enrolled 641 infants born weighing between 401 and 1000 grams. As detailed in a report published in October 2025, the study randomly assigned infants to receive either budesonide (0.25 mg/kg) mixed with poractant alfa surfactant, or surfactant alone, within 50 hours of birth. Surfactant is routinely given to premature babies to facilitate them breathe by reducing surface tension in the lungs. The trial was stopped prematurely, at 50% enrollment, after an interim analysis revealed it was unlikely to demonstrate a significant benefit.
The primary outcome – physiologic BPD or death by 36 weeks’ postmenstrual age – occurred in 68.5% of the budesonide + surfactant group and 67.9% of the surfactant-alone group. The adjusted relative risk was 1.00 (95% Confidence Interval: 0.90-1.11), indicating no statistically significant difference. Mortality rates were likewise comparable, at 15.3% versus 13.2% (adjusted relative risk, 1.13. 95% CI, 0.78-1.64). BPD rates among survivors to 36 weeks were similarly aligned (62.9% vs 63%).
These findings echo those of the earlier Premature Infants Treated With Lung Surfactant Using Steroid Supplement (PLUSS) trial, which also failed to demonstrate a benefit from steroid supplementation. A recent editorial in JAMA highlighted the consistency between the BiB and PLUSS trials, reinforcing the need to re-evaluate current practices.
The Role of Budesonide and Surfactant
Budesonide is a potent glucocorticoid, a type of steroid known for its anti-inflammatory properties. The rationale for its use in preterm infants is to reduce lung inflammation and prevent the development of BPD. Surfactant, as mentioned, is a substance that coats the air sacs in the lungs, preventing them from collapsing. We see a standard of care for premature infants, but researchers have explored whether adding steroids to surfactant could enhance its effectiveness.
The BiB trial used poractant alfa, a synthetic surfactant derived from porcine lung extract. The study protocol involved administering one to two doses of the assigned treatment via endotracheal tube, a breathing tube inserted into the trachea. Researchers meticulously tracked a range of physiological parameters and clinical outcomes to assess the impact of budesonide.
Implications for Clinical Practice and Future Research
The negative results of the BiB trial raise important questions about the routine use of budesonide in extremely preterm infants. While the drug is not without potential side effects – including adrenal suppression and increased risk of infection – the hope was that the benefits would outweigh the risks. The trial’s findings suggest that this may not be the case.
“These results suggest that the widespread use of budesonide in this population may need to be reconsidered,” says Dr. Emily Carter, a neonatologist at Charité – Universitätsmedizin Berlin, who was not involved in the study. “We need to focus on optimizing other aspects of care, such as minimizing ventilation and providing gentle handling, to prevent BPD.”
The study, registered on ClinicalTrials.gov under the identifier NCT04545866, also highlights the challenges of conducting large-scale clinical trials in vulnerable populations. The early termination of the BiB trial, while justified by the futility analysis, underscores the ethical considerations involved in stopping a study before it is fully completed.
Understanding Bronchopulmonary Dysplasia
BPD isn’t a single disease, but rather a spectrum of lung abnormalities. Severity can range from mild, with minimal long-term effects, to severe, requiring ongoing medical intervention. Symptoms can include rapid breathing, wheezing, coughing, and difficulty feeding. Long-term consequences of BPD can include impaired lung function, increased susceptibility to respiratory infections, and neurodevelopmental delays.
The exact causes of BPD are complex and multifactorial. Prematurity itself is a major risk factor, as the lungs are not fully developed at birth. Mechanical ventilation, while life-saving, can also cause lung injury. Other contributing factors include infection, inflammation, and genetic predisposition.
What Happens Next?
Researchers are continuing to investigate potential strategies for preventing and treating BPD. Areas of focus include novel anti-inflammatory therapies, improved ventilation techniques, and strategies to promote lung development. Further research is also needed to identify infants who are most likely to benefit from specific interventions. The European Respiratory Society is hosting a conference in September 2026 where modern data on BPD prevention will be presented.
The BiB trial’s findings serve as a crucial reminder that even well-intentioned interventions may not always yield the desired results. Rigorous clinical trials are essential to ensure that medical practices are based on solid evidence and that the best possible care is provided to vulnerable patients.
This research underscores the importance of a nuanced approach to neonatal care, prioritizing individualized treatment plans and continuous monitoring of outcomes. The quest for effective BPD prevention continues, driven by the unwavering commitment of researchers and clinicians to improve the lives of premature infants.
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