Supplementary Material for: Inhaled Glucocorticoids and Pneumonia in Preterm Infants: Post Hoc Results from the NEuroSIS Trial

Background: Inhaled glucocorticoids may increase the risk of pneumonia in adults. Thus, respiratory infections may be a potential explanation for the non-significantly increased mortality seen in the glucocorticoid group in the largest randomized trial on inhaled glucocorticoids for preventing bronchopulmonary dysplasia in preterm infants published to date (NEuroSIS). Objective: To evaluate the effect of inhaled budesonide on the risk of death due to respiratory infections in the NEuroSIS trial. Methods: We performed post hoc analyses of prospectively collected data from 856 preterm infants on presumed but not culture-proven sepsis and antimicrobial drug use. Additionally, pulmonary complications reported on adverse event forms, death certificates and autopsy reports were compared between study groups. Results: Treatment groups did not differ in the number of episodes with suspected sepsis (184/437 [42.1%] in the budesonide vs. 171/419 [40.8%] in the placebo group). Neither the number of patients receiving antimicrobial drugs nor the length of antimicrobial treatment differed between groups. Our analyses for pulmonary adverse events as well as for pulmonary complications reported on death certificates and autopsy reports did not suggest a negative impact of inhaled budesonide on these outcomes. Conclusion: The current analysis does not support the assumption that respiratory tract infections explain the increased mortality seen in the glucocorticoid group in the NEuroSIS trial.