Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia
Dirk Bassler, Eric S Shinwell, Mikko Hallman, Pierre-Henri Jarreau, Richard Plavka, Virgilio Carnielli, Christoph Meisner, Corinna Engel, Alexander Koch, Karen Kreutzer, Johannes N van den Anker, Matthias Schwab, Henry L Halliday, Christian F Poets, Neonatal European Study of Inhaled Steroids Trial Group, Blanka Zlatohlávková, Daniela Marková, Alena Fleischnerová, Barbara Seipolt, Beate Walter, Emmanuel Lopez, Lucie Massie-Vuillemin, Eve Delort-Germes, Fabienne Cautru, Justin Richardson, Shlomith Dadoun, Esther Goldstein, Gabriele von Oldershausen, Beate Schneider, Anna D Koluch, Insa Hoffmann, Jiri Dort, Eva Dortova, Lenka Fromlova, Florence Flamein, Sébastien Mur, Laurent Storme, Päivi Olsen, Heli Helander, Riitta Vikeväninen, Orna Flidel-Rimon, Ada Juster Reicher, M Anneli Kari, Aulikki Lano, Riina Puosi, Sture Andersson, Leena Kivinen, Anniina Maaria Manninen, Virpi Maarit Ylihärsilä, Outi Tammela, Stefano Nobile, Anna M Peretti, Anja Stein, Ursula Felderhoff-Müser, Julia Hobrecht, Renáta Poláčková, Sylvie Franková, Marcela Kvardová, Marek Kučera, Tomáš Juren, Marie Kyselková, Hana Jahnová, Johannes Pöschl, Bernd Beedgen, Sebastian Ronellenfitsch, Gitta Reuner, Jozef Macko, Barbara Tesařová, Simona Vyoralová, Miloš Černý, Radim Brabec, Ladislava Doležalová, Jakub Tkaczyk, Sarah Kabisch, Monika Wolf, Thilo Diehl, David Bader, Bella Sandler, Benjamin Bar-Oz, Elena Golzand, Maya Yaari, Jan-Holger Schiffmann, Stefan Schäfer, Bettina Bohnhorst, Stephanie Ehlers, Christoph Jacobi, Carolin Böhne, Helmut Küster, Elke Hobbiebrunken, Vanessa Gouder de Beauregard, Dominique Haumont, Vinciane Vlieghe, Anne-Britt Johansson, René F Kornelisse, Renate M C Swarte, Lisotte E Rotsde Vries, Ellen van’t Verlaat, Ita Litmanovitz, Shmuel Arnon, Paolo Gancia, Giulia Pomero, Cristina Dalmazzo, Eleonora Briatore, Elisa Beccaria, Manuela Martino, Wim Decaluwe, Alexandra Casaer, Ann Oostra, Nina Vens, Johanna Deslee, Eveline Rondelez, Tuuli Metsvaht, Heili Varendi, Mark Schoberer, Sonja Trepels-Kottek, Thorsten Orlikowsky, Elie Saliba, Silvia Maria Borgione, Patrizia Strola, Claudio Martano, Carlos Menendez-Castro, Wolfgang Rascher, Regina Trollmann, Ulla Sankilampi, Geneviève Malfilâtre, Julie De Buyst, Paolo Ghirri, Rosa T Scaramuzzo, Giovanna Verlato, Monica Mantegazza, Jacob Aranda, Elaine Boyle, Robin Roberts, Ruth Bösel, Sebastian Claus, Clemens Lässing, Janaina Nufer, Birgit Schuler, Susanne Stoppel, Dirk Bassler, Eric S Shinwell, Mikko Hallman, Pierre-Henri Jarreau, Richard Plavka, Virgilio Carnielli, Christoph Meisner, Corinna Engel, Alexander Koch, Karen Kreutzer, Johannes N van den Anker, Matthias Schwab, Henry L Halliday, Christian F Poets, Neonatal European Study of Inhaled Steroids Trial Group, Blanka Zlatohlávková, Daniela Marková, Alena Fleischnerová, Barbara Seipolt, Beate Walter, Emmanuel Lopez, Lucie Massie-Vuillemin, Eve Delort-Germes, Fabienne Cautru, Justin Richardson, Shlomith Dadoun, Esther Goldstein, Gabriele von Oldershausen, Beate Schneider, Anna D Koluch, Insa Hoffmann, Jiri Dort, Eva Dortova, Lenka Fromlova, Florence Flamein, Sébastien Mur, Laurent Storme, Päivi Olsen, Heli Helander, Riitta Vikeväninen, Orna Flidel-Rimon, Ada Juster Reicher, M Anneli Kari, Aulikki Lano, Riina Puosi, Sture Andersson, Leena Kivinen, Anniina Maaria Manninen, Virpi Maarit Ylihärsilä, Outi Tammela, Stefano Nobile, Anna M Peretti, Anja Stein, Ursula Felderhoff-Müser, Julia Hobrecht, Renáta Poláčková, Sylvie Franková, Marcela Kvardová, Marek Kučera, Tomáš Juren, Marie Kyselková, Hana Jahnová, Johannes Pöschl, Bernd Beedgen, Sebastian Ronellenfitsch, Gitta Reuner, Jozef Macko, Barbara Tesařová, Simona Vyoralová, Miloš Černý, Radim Brabec, Ladislava Doležalová, Jakub Tkaczyk, Sarah Kabisch, Monika Wolf, Thilo Diehl, David Bader, Bella Sandler, Benjamin Bar-Oz, Elena Golzand, Maya Yaari, Jan-Holger Schiffmann, Stefan Schäfer, Bettina Bohnhorst, Stephanie Ehlers, Christoph Jacobi, Carolin Böhne, Helmut Küster, Elke Hobbiebrunken, Vanessa Gouder de Beauregard, Dominique Haumont, Vinciane Vlieghe, Anne-Britt Johansson, René F Kornelisse, Renate M C Swarte, Lisotte E Rotsde Vries, Ellen van’t Verlaat, Ita Litmanovitz, Shmuel Arnon, Paolo Gancia, Giulia Pomero, Cristina Dalmazzo, Eleonora Briatore, Elisa Beccaria, Manuela Martino, Wim Decaluwe, Alexandra Casaer, Ann Oostra, Nina Vens, Johanna Deslee, Eveline Rondelez, Tuuli Metsvaht, Heili Varendi, Mark Schoberer, Sonja Trepels-Kottek, Thorsten Orlikowsky, Elie Saliba, Silvia Maria Borgione, Patrizia Strola, Claudio Martano, Carlos Menendez-Castro, Wolfgang Rascher, Regina Trollmann, Ulla Sankilampi, Geneviève Malfilâtre, Julie De Buyst, Paolo Ghirri, Rosa T Scaramuzzo, Giovanna Verlato, Monica Mantegazza, Jacob Aranda, Elaine Boyle, Robin Roberts, Ruth Bösel, Sebastian Claus, Clemens Lässing, Janaina Nufer, Birgit Schuler, Susanne Stoppel
Abstract
Background: The long-term effects on neurodevelopment of the use of inhaled glucocorticoids in extremely preterm infants for the prevention or treatment of bronchopulmonary dysplasia are uncertain.
Methods: We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to receive early (within 24 hours after birth) inhaled budesonide or placebo. The prespecified secondary long-term outcome was neurodevelopmental disability among survivors, defined as a composite of cerebral palsy, cognitive delay (a Mental Development Index score of <85 [1 SD below the mean of 100] on the Bayley Scales of Infant Development, Second Edition, with higher scores on the scale indicating better performance), deafness, or blindness at a corrected age of 18 to 22 months.
Results: Adequate data on the prespecified composite long-term outcome were available for 629 infants. Of these infants, 148 (48.1%) of 308 infants assigned to budesonide had neurodevelopmental disability, as compared with 165 (51.4%) of 321 infants assigned to placebo (relative risk, adjusted for gestational age, 0.93; 95% confidence interval [CI], 0.80 to 1.09; P=0.40). There was no significant difference in any of the individual components of the prespecified outcome. There were more deaths in the budesonide group than in the placebo group (82 [19.9%] of 413 infants vs. 58 [14.5%] of 400 infants for whom vital status was available; relative risk, 1.37; 95% CI, 1.01 to 1.86; P=0.04).
Conclusions: Among surviving extremely preterm infants, the rate of neurodevelopmental disability at 2 years did not differ significantly between infants who received early inhaled budesonide for the prevention of bronchopulmonary dysplasia and those who received placebo, but the mortality rate was higher among those who received budesonide. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190 .).
Source: PubMed