Dirk Bassler1, Richard Plavka, Eric S Shinwell, Mikko Hallman, Pierre-Henri Jarreau, Virgilio Carnielli, Johannes N Van den Anker, Christoph Meisner, Corinna Engel, Matthias Schwab, Henry L Halliday, Christian F Poets. 1. From the Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich (D.B.), and the Department of Pediatric Pharmacology, University Children's Hospital, Basel (J.N.A.) - both in Switzerland; the Department of Neonatology (D.B., C.F.P.) and the Center for Pediatric Clinical Studies (C.E.), University Children's Hospital Tübingen, and the Institute for Clinical Epidemiology and Applied Biometry (C.M.) and the Department of Clinical Pharmacology (M.S.), University Hospital Tübingen, Tübingen, and Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart (M.S.) - all in Germany; Charles University, General University Hospital and First Faculty of Medicine, Prague, Czech Republic (R.P.); Ziv Medical Center, Zefat, Bar-Ilan University, Ramat Gan, Israel (E.S.S.); the Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland (M.H.); Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire, Université Paris Descartes, Hôpital Cochin, Service de Médecine et Réanimation néonatales de Port-Royal, Paris (P.-H.J.); Polytechnic University of Marche, Salesi Children's Hospital, Ancona, Italy (V.C.); the Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC (J.N.A.); Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands (J.N.A.); and the Department of Child Health at Queen's University Belfast, Institute of Clinical Science, Belfast, Northern Ireland (H.L.H.).
Abstract
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 tobudesonide 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. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.).
RCT Entities:
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. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.).
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