Early intratracheal budesonide has little to no effect on survival free of bronchopulmonary dysplasia | Image Credit: © Rasi - © Rasi - stock.adobe.com.

Among extremely preterm infants who were receiving surfactant, early intratracheal budesonide could have little to no effect on survival free of bronchopulmonary dysplasia (BPD), according to findings of a recent study published in JAMA Network.¹

Background

BPD, a common adverse outcome in extremely preterm infants born at less than 28 weeks' gestation, is present in approximately half of infants born extremely preterm (approximately 600,000 per year worldwide).² Survivors of BPD are at a greater risk of early childhood respiratory illnesses, asthma, and adverse neurodevelopmental outcomes, compared to infants who do not develop BPD.¹

Optimal regimen of anti-inflammatory corticosteroids remains unclear, despite them being the focus of preventive efforts for BPD.¹

"Although systemic (intravenous or enteral) corticosteroids reduce BPD risk, when they are administered in the first week after birth or at a high cumulative dose, they are associated with harm, including increased risk of cerebral palsy in survivors," wrote the study investigators. "Similarly, prolonged neonatal courses of inhaled corticosteroids (eg, via a metered dose inhaler) have been associated with increased mortality."¹

In a pair of previous randomized clinical trials, results demonstrated that intratracheal budesonide, 0.25 mg / kg, mixed with surfactant, compared with surfactant only, was associated with a more than one-third reduced risk in the combined outcome of death or BPD, according to the current study. As a result, the authors stated some centers have introduced intratracheal budesonide into routine care, though a large pragmatic trial assessing effectiveness of this therapy is needed across a broader group of extremely preterm infants.¹

"The current trial, Preventing Lung Disease Using Surfactant + Steroid (PLUSS), was undertaken to determine whether intratracheal budesonide mixed with surfactant benefits extremely preterm infants," the authors wrote.¹

The primary endpoint of the study was survival free of BPD at 36 weeks' postmenstrual age.¹

Study details and results

The trial was a double-blind, randomized, and conducted in 21 neonatal units in Australia, New Zealand, Canada, and Singapore. It enrolled infants born at less than 28 weeks' gestation and less than 48 hours old who were mechanically ventilated, or who were receiving non-invasive respiratory support, with a clinical decision to treat with surfactant.¹

Infants were randomly allocated at a 1:1 ratio to receive budesonide, 0.25 mg / kg, mixed with surfactant administered via endotracheal tube or thin catheter, or surfactant only.¹

The primary analysis featured 1059 infants, resulting in 524 in the budesonide and surfactant group and 535 in the surfactant-only group. Infants had a mean gestational age of 25.6 weeks (SD 1.3 weeks), and a mean birth weight of 775 g (SD, 197 g). Of those included in the trial, 55.3% were male.¹

In the budesonide and surfactant group, survival free of BPD occurred in 25.6% of infants (n = 134) and in 22.6% (n = 121) of infants in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, −2.1% to 7.4%]).¹

At the 36-week postmenstrual age (MPA) primary endpoint, 83.2% of infants were alive in the budesonide and surfactant group and 80.6% were alive in the surfactant-only group. Of these, 69.3% and 71.9% were diagnosed with BPD, respectively, according to study results.¹

Conclusion

"In extremely preterm infants with respiratory distress syndrome receiving surfactant, early intratracheal budesonide may have little to no effect on the risk of survival free of BPD at 36 weeks’ PMA," the study authors concluded. "Longer-term outcomes of the current trial at 2 years, as well as the results of other similar large randomized clinical trials will be important to fully characterize the effectiveness and safety of intratracheal budesonide and determine its role in clinical practice.¹

Reference:

Manley BJ, Kamlin COF, Donath SM, et al. Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants: The PLUSS Randomized Clinical Trial. JAMA. Published online November 11, 2024. doi:10.1001/jama.2024.17380