Early inhaled budesonide for the prevention of bronchopulmonary dysplasia

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P = 0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P = 0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P = 0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P = 0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P = 0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality

The impact of inhaled bronchodilators on bronchopulmonary dysplasia: a nonrandomized comparison from the NEuroSIS trial

BACKGROUND Inhaled bronchodilators improve pulmonary function. Their effects on bronchopulmonary dysplasia (BPD) are uncertain. We assessed the efficacy of early inhaled bronchodilators on the risk of BPD and death in extremely preterm infants. METHODS We performed a post-hoc analysis of prospectively collected data from the Neonatal European Study of Inhaled Steroids (NEuroSIS). In NEuroSIS, 863 extremely preterm infants were randomly assigned to receive early inhaled budesonide or placebo. We now performed nonrandomized comparisons between infants that participated in the NEUROSIS trial and either received early (within the first 48 h of life) bronchodilators or no bronchodilators. Groups were assembled according to predefined criteria stated in the study protocol and we used the same prespecified primary outcome as in the main study, a composite of BPD and death at a postmenstrual age of 36 weeks. RESULTS Treatment groups did not differ significantly in the composite outcome of BPD and death at 36 weeks postmenstrual age: bronchodilator group (20/46; 43.5%), versus 349/810 (43.1%) in the no bronchodilator group; (p = .97). Analyzed by individual components, there were no significant differences in BPD and death rates between the groups. DISCUSSION Based on our analyses, early inhaled bronchodilators did not reduce the risk of BPD and death in extremely preterm infants

The impact of inhaled bronchodilators on bronchopulmonary dysplasia: a nonrandomized comparison from the NEuroSIS trial

BACKGROUND Inhaled bronchodilators improve pulmonary function. Their effects on bronchopulmonary dysplasia (BPD) are uncertain. We assessed the efficacy of early inhaled bronchodilators on the risk of BPD and death in extremely preterm infants. METHODS We performed a post-hoc analysis of prospectively collected data from the Neonatal European Study of Inhaled Steroids (NEuroSIS). In NEuroSIS, 863 extremely preterm infants were randomly assigned to receive early inhaled budesonide or placebo. We now performed nonrandomized comparisons between infants that participated in the NEUROSIS trial and either received early (within the first 48 h of life) bronchodilators or no bronchodilators. Groups were assembled according to predefined criteria stated in the study protocol and we used the same prespecified primary outcome as in the main study, a composite of BPD and death at a postmenstrual age of 36 weeks. RESULTS Treatment groups did not differ significantly in the composite outcome of BPD and death at 36 weeks postmenstrual age: bronchodilator group (20/46; 43.5%), versus 349/810 (43.1%) in the no bronchodilator group; (p = .97). Analyzed by individual components, there were no significant differences in BPD and death rates between the groups. DISCUSSION Based on our analyses, early inhaled bronchodilators did not reduce the risk of BPD and death in extremely preterm infants

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

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

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

<p><b><i>Background:</i></b> 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). <b><i>Objective:</i></b> To evaluate the effect of inhaled budesonide on the risk of death due to respiratory infections in the NEuroSIS trial. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.</p