As neonatologists have been able save more babies that have born prematurely, the problem of bronchopulmonary dysplasia (BPD) has loomed larger. BPD occurs in preterm infants (born at less than 28 weeks of gestation) or in infants with extremely low birth weight (less than 1000 grams at birth). It stems from a variety of factors, including underdeveloped lung tissue, inflammation, and mechanical injury associated with ventilatory support (McEvoy et al, 2014). These factors lead to acute lung injury and subsequently, impaired repair and growth. BPD is associated with significant neonatal mortality and is in need of better therapy.
Randomized clinical trials have shown that systemic glucocorticoids can effectively decrease the incidence of BPD, but they may be associated with adverse effects such as intestinal perforation and cerebral palsy. To avoid the risks of systemic glucocorticoids, Bassler et al performed a multinational, randomized placebo-controlled trial, published in this week’s issue of NEJM, to test the effectiveness of budesonide, an inhaled glucocorticoid, to prevent BPD in preterm infants; the hope is that inhaled glucocorticoids will have local benefits in the lungs without getting into the systemic circulation. Of the 856 infants evaluated for the primary outcomes (development of BPD or death), the observed rate was 40.0% in the budesonide group and 46.3% in the placebo group (relative risk, stratified for gestational age, 0.86; 95% CI, 0.75-1.00; P=0.053). The composite outcome is driven primarily by a decrease in the risk of BPD (27.8% in the budesonide group vs. 38.0% in the placebo group, P=0.004) combined with a trend towards increased mortality in the budesonide group (16.9% vs. 13.6% in the placebo group, P=0.17). Thus, while inhaled corticosteroids may effectively prevent BPD, its ultimate benefit for neonates is unclear.
In an accompanying editorial, Barbara Schmidt, MD, points out that although the difference in mortality rate may be due to chance, the increased mortality could be due to pneumonia, which is a well-established risk with inhaled glucocorticoids in adults. Although no significant difference in the rate of sepsis or infection as a cause of death between the two groups was found, autopsies were only performed in 1/3 of the cases. These results, unfortunately, do not lead us towards any more clarity on how to prevent BPD, as it appears that inhaled glucocorticoids carry risks of their own.