Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia
Dirk Bassler, 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, NEUROSIS Trial Group, Richard Plavka, Barbara Seipolt, Pierre-Henri Jarreau, Justin Richardson, Shlomith Dadoun, Dirk Bassler, Christian F Poets, Karen Kreutzer, Alexander Koch, Beate Schneider, Anna D Koluch, Jiri Dort, Pavel Huml, Martin Matas, Eva Dortová, Alice Mockova, Lucie Šusterová, Thomas Pennaforte, Mikko Hallman, Outi Aikio, Riitta Vikeväinen, Mari Mahlman, Eric S Shinwell, Orna Flidel Rimon, Ada Juster Reicher, Ilya Rozin, Michael Levin, M Anneli Kari, Sture Andersson, Ilkka Ketola, Outi Tammela, Virgilio Carnielli, Stefano Nobile, Anja Stein, Ursula Felderhoff-Müser, Renáta Poláčková, Tomáš Juren, Marek Kučera, Johannes Pöschl, Bernd Beedgen, Sebastian Ronellenfitsch, Jozef Macko, Miloš Cerný, Sarah Kabisch, David Bader, Benjamin Bar-Oz, Elena Golzand, Maya Yaari, Holger Schiffmann, Stefan Schäfer, Bettina Bohnhorst, Stephanie Ehlers, Helmut Küster, Nils Lazer, Vanessa Gouder De Beauregard, Dominique Haumont, Vinciane Vlieghe, Anne-Britt Johansson, John van den Anker, René F Kornelisse, Dick Tibboel, Ita Litmanovitz, Shmuel Arnon, Paolo Gancia, Cristina Dalmazzo, Giulia Pomero, Wim Decaluwe, Tuuli Metsvaht, Heili Varendi, Mark Schoberer, Sonja Trepels-Kottek, Karine Norbert, Elie Saliba, Claudio Martano, Silvia Borgione, Carlos Menendez-Castro, Wolfgang Rascher, Ulla Sankilampi, Geneviève Malfilâtre, Paolo Ghirri, Lino Chiandetti, Dirk Bassler, Virgilio Carnielli, Henry L Halliday, Mikko Hallman, Pierre-Henri Jarreau, Richard Plavka, Christian F Poets, Matthias Schwab, Eric S Shinwell, John van den Anker, Jacob Aranda, Elaine Boyle, Robin Roberts, Christoph Meisner, Corinna Engel, Dirk Bassler, 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, NEUROSIS Trial Group, Richard Plavka, Barbara Seipolt, Pierre-Henri Jarreau, Justin Richardson, Shlomith Dadoun, Dirk Bassler, Christian F Poets, Karen Kreutzer, Alexander Koch, Beate Schneider, Anna D Koluch, Jiri Dort, Pavel Huml, Martin Matas, Eva Dortová, Alice Mockova, Lucie Šusterová, Thomas Pennaforte, Mikko Hallman, Outi Aikio, Riitta Vikeväinen, Mari Mahlman, Eric S Shinwell, Orna Flidel Rimon, Ada Juster Reicher, Ilya Rozin, Michael Levin, M Anneli Kari, Sture Andersson, Ilkka Ketola, Outi Tammela, Virgilio Carnielli, Stefano Nobile, Anja Stein, Ursula Felderhoff-Müser, Renáta Poláčková, Tomáš Juren, Marek Kučera, Johannes Pöschl, Bernd Beedgen, Sebastian Ronellenfitsch, Jozef Macko, Miloš Cerný, Sarah Kabisch, David Bader, Benjamin Bar-Oz, Elena Golzand, Maya Yaari, Holger Schiffmann, Stefan Schäfer, Bettina Bohnhorst, Stephanie Ehlers, Helmut Küster, Nils Lazer, Vanessa Gouder De Beauregard, Dominique Haumont, Vinciane Vlieghe, Anne-Britt Johansson, John van den Anker, René F Kornelisse, Dick Tibboel, Ita Litmanovitz, Shmuel Arnon, Paolo Gancia, Cristina Dalmazzo, Giulia Pomero, Wim Decaluwe, Tuuli Metsvaht, Heili Varendi, Mark Schoberer, Sonja Trepels-Kottek, Karine Norbert, Elie Saliba, Claudio Martano, Silvia Borgione, Carlos Menendez-Castro, Wolfgang Rascher, Ulla Sankilampi, Geneviève Malfilâtre, Paolo Ghirri, Lino Chiandetti, Dirk Bassler, Virgilio Carnielli, Henry L Halliday, Mikko Hallman, Pierre-Henri Jarreau, Richard Plavka, Christian F Poets, Matthias Schwab, Eric S Shinwell, John van den Anker, Jacob Aranda, Elaine Boyle, Robin Roberts, Christoph Meisner, Corinna Engel
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 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.).
Source: PubMed