A multicenter clinical trial has found that intratracheal steroids do not reduce the risk of lung disease or death in extremely preterm infants, according to a study recently published in JAMA.
The results challenge earlier findings from smaller studies in which investigators added the anti-inflammatory drug budesonide to the current standard surfactant therapy in hopes of reducing the risk of chronic lung disease or death in extremely preterm infants, said Marta Perez, MD, assistant professor of Pediatrics in the Division of Neonatology, who was a co-author of the study.
“Bronchopulmonary dysplasia (BPD), a long-term chronic respiratory insufficiency, is one of the most common sequelae of prematurity that we see,” Perez said. “Despite advances in neonatal care, rates of BPD continue to be high.”
The study, led by the National Institute of Child Health and Human Development’s Neonatal Research Network, enrolled 641 infants born between 22 and 28 weeks of gestation or weighing 401 to 1000 grams. All participants received surfactant therapy within 50 hours of birth, with half randomized to also receive an added dose of budesonide.
Despite hopes that the combination therapy might improve outcomes, the trial was halted early after an interim analysis showed no significant benefit. The incidence of bronchopulmonary dysplasia or death by 36 weeks of age was nearly identical between the two groups: 68.5 percent in the budesonide-surfactant group versus 67.9 percent in the surfactant-only group.
The findings contrast with earlier, smaller trials that had suggested a potential benefit of combining budesonide with surfactant, a standard therapy in which the substance is administered to line the air sacs in the lungs and help prevent them from collapsing. However, those studies lacked the scale and rigor of the most recent multicenter trial, according to the authors.
Moving forward, Perez and her collaborators aim to study if intratracheal steroids can help preterm babies who experience inflammation or have certain genetic predispositions, she said.
“We still don’t know if tailoring this approach to children with certain predisposing factors such as a high degree of inflammation in their lungs or those who experienced significant prenatal inflammation, could make it more useful,” Perez said.
BPD remains a leading cause of long-term respiratory and developmental complications in premature infants. While surfactant therapy is a cornerstone of neonatal care, Perez said investigators continue to search for treatments that can further reduce the risk of this chronic lung disease.
“While we have been lucky in neonatology to have a lot of data from large, randomized control trials, we still have many clinical questions, and there’s a lot of uncertainty about ways to treat premature babies and ways we could tailor our therapeutic approaches,” Perez said. “So, our work has to continue.”
The study was funded by the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the National Center for Advancing Translational Sciences, through cooperative agreements for the Neonatal Research Network.
