{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:24:32Z","timestamp":1787826272925,"version":"build-2784847793"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Pediatr"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"Importance<\/jats:title>Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023.<\/jats:p><\/jats:sec>Intervention<\/jats:title>Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was intubation in the delivery room for bradycardia and\/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P<\/jats:italic> = .04).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks\u2019 GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>EudraCT: 2016-004198-41<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapediatrics.2023.5082","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T16:08:08Z","timestamp":1702310888000},"page":"117","source":"Crossref","is-referenced-by-count":12,"title":["Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth"],"prefix":"10.1001","volume":"178","author":[{"given":"Madeleine C.","family":"Murphy","sequence":"first","affiliation":[{"name":"National Maternity Hospital, Dublin, Ireland"},{"name":"School of Medicine, University College Dublin, Dublin, Ireland"},{"name":"National Children\u2019s Research Centre, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Miletin","sequence":"additional","affiliation":[{"name":"Coombe Women and Infants University Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Klingenberg","sequence":"additional","affiliation":[{"name":"Paediatric Research Group, Faculty of Health Sciences, UiT\u2013The Arctic University of Norway, Troms\u00f8, Norway"},{"name":"Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J\u00f8rgen","family":"Guthe","sequence":"additional","affiliation":[{"name":"Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Rigo","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Plavka","sequence":"additional","affiliation":[{"name":"Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajsa","family":"Bohlin","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Stockholm, Sweden"},{"name":"Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almerinda","family":"Barroso Pereira","sequence":"additional","affiliation":[{"name":"Hospital de Braga, Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Juren","sequence":"additional","affiliation":[{"name":"University Hospital Brno, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekele","family":"Alih","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Galligan","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, School of Medicine, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm P. F.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"National Maternity Hospital, Dublin, Ireland"},{"name":"School of Medicine, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5, pt 1","key":"poi230078r1","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1001\/archpedi.1959.02070010519001","article-title":"Surface properties in relation to atelectasis and hyaline membrane disease.","volume":"97","author":"Avery","year":"1959","journal-title":"AMA J Dis Child"},{"issue":"8159","key":"poi230078r2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0140-6736(80)90489-4","article-title":"Artificial surfactant therapy in hyaline-membrane disease.","volume":"1","author":"Fujiwara","year":"1980","journal-title":"Lancet"},{"issue":"2","key":"poi230078r3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1542\/peds.76.2.145","article-title":"Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.","volume":"76","author":"Enhorning","year":"1985","journal-title":"Pediatrics"},{"issue":"6578","key":"poi230078r4","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1136\/bmj.294.6578.991","article-title":"Ten Centre trial of artificial surfactant (artificial lung expanding compound) in very premature babies.","volume":"294","author":"Ten Centre Study Group","year":"1987","journal-title":"BMJ (Clin Res Ed)"},{"issue":"13","key":"poi230078r5","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1056\/NEJM198609253151301","article-title":"Prophylactic treatment of very premature infants with human surfactant.","volume":"315","author":"Merritt","year":"1986","journal-title":"N Engl J Med"},{"issue":"2","key":"poi230078r6","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1159\/000444918","article-title":"Ventilation-induced brain injury in preterm neonates: a review of potential therapies.","volume":"110","author":"Barton","year":"2016","journal-title":"Neonatology"},{"issue":"11","key":"poi230078r7","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1002\/lary.v131.11","article-title":"Intubation-related laryngeal deficiency and vocal fold immobility in pediatric premature patients.","volume":"131","author":"Zur","year":"2021","journal-title":"Laryngoscope"},{"issue":"3","key":"poi230078r8","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3390\/jcm11030557","article-title":"Ventilation-induced lung injury (VILI) in neonates: evidence-based concepts and lung-protective strategies.","volume":"11","author":"Kalikkot Thekkeveedu","year":"2022","journal-title":"J Clin Med"},{"issue":"3","key":"poi230078r9","doi-asserted-by":"publisher","DOI":"10.1002\/14651858","article-title":"Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants.","author":"Rojas-Reyes","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"issue":"7","key":"poi230078r10","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1056\/NEJMoa072788","article-title":"Nasal CPAP or intubation at birth for very preterm infants.","volume":"358","author":"Morley","year":"2008","journal-title":"N Engl J Med"},{"issue":"5","key":"poi230078r11","doi-asserted-by":"publisher","first-page":"e1069","DOI":"10.1542\/peds.2010-3848","article-title":"Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates.","volume":"128","author":"Dunn","year":"2011","journal-title":"Pediatrics"},{"issue":"21","key":"poi230078r12","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1056\/NEJMoa0911783","article-title":"Early CPAP versus surfactant in extremely preterm infants.","volume":"362","author":"Finer","year":"2010","journal-title":"N Engl J Med"},{"issue":"9803","key":"poi230078r13","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/S0140-6736(11)60986-0","article-title":"Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial.","volume":"378","author":"G\u00f6pel","year":"2011","journal-title":"Lancet"},{"issue":"5","key":"poi230078r14","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1136\/archdischild-2020-319763","article-title":"Comparative efficacy of methods for surfactant administration: a network meta-analysis.","volume":"106","author":"Bellos","year":"2021","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"2","key":"poi230078r15","doi-asserted-by":"publisher","first-page":"F122","DOI":"10.1136\/archdischild-2011-301314","article-title":"Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure.","volume":"98","author":"Dargaville","year":"2013","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"2","key":"poi230078r16","doi-asserted-by":"publisher","first-page":"e502","DOI":"10.1542\/peds.2012-0603","article-title":"Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial.","volume":"131","author":"Kanmaz","year":"2013","journal-title":"Pediatrics"},{"issue":"8","key":"poi230078r17","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1001\/jamapediatrics.2015.0504","article-title":"Nonintubated surfactant application vs conventional therapy in extremely preterm infants: a randomized clinical trial.","volume":"169","author":"Kribs","year":"2015","journal-title":"JAMA Pediatr"},{"issue":"5","key":"poi230078r18","article-title":"Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome.","volume":"5","author":"Abdel-Latif","year":"2021","journal-title":"Cochrane Database Syst Rev"},{"issue":"24","key":"poi230078r19","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1001\/jama.2021.21892","article-title":"Effect of minimally invasive surfactant therapy vs sham treatment on death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: the OPTIMIST-A randomized clinical trial.","volume":"326","author":"Dargaville","year":"2021","journal-title":"JAMA"},{"key":"poi230078r20","doi-asserted-by":"publisher","author":"Berggren","year":"2000","DOI":"10.1080\/080352500750028195"},{"issue":"5","key":"poi230078r21","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1089\/jamp.2009.0758","article-title":"An open label, pilot study of Aerosurf\u00ae combined with nCPAP to prevent RDS in preterm neonates.","volume":"23","author":"Finer","year":"2010","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"issue":"3","key":"poi230078r22","doi-asserted-by":"publisher","first-page":"F313","DOI":"10.1136\/archdischild-2018-315051","article-title":"Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial.","volume":"104","author":"Minocchieri","year":"2019","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"poi230078r23","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008310.pub2","article-title":"Nebulised surfactant in preterm infants with or at risk of respiratory distress syndrome.","volume":"10","author":"Abdel-Latif","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"poi230078r24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1136\/archdischild-2022-324519","article-title":"Prophylactic surfactant nebulisation for the early aeration of the preterm lung: a randomised clinical trial.","volume":"108","author":"Gaertner","year":"2023","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"5","key":"poi230078r25","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-3967","article-title":"Aerosolized calfactant for newborns with respiratory distress: a randomized trial.","volume":"146","author":"Cummings","year":"2020","journal-title":"Pediatrics"},{"issue":"3","key":"poi230078r26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1055\/s-00000009","article-title":"Administration of rescue surfactant by laryngeal mask airway: lessons from a pilot trial.","volume":"30","author":"Attridge","year":"2013","journal-title":"Am J Perinatol"},{"key":"poi230078r27","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jpeds.2017.09.068","article-title":"Laryngeal mask airway for surfactant administration in neonates: a randomized, controlled trial.","volume":"193","author":"Roberts","year":"2018","journal-title":"J Pediatr"},{"issue":"7","key":"poi230078r28","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008309.pub2","article-title":"Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome.","author":"Abdel-Latif","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"poi230078r29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2022.10.009","article-title":"Randomized trial of surfactant therapy via laryngeal mask airway versus brief tracheal intubation in neonates born preterm.","volume":"254","author":"Gallup","year":"2023","journal-title":"J Pediatr"},{"issue":"5 pt 1","key":"poi230078r30","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1203\/01.PDR.0000156502.84909.BC","article-title":"Spontaneous breathing or mechanical ventilation alters lung compliance and tissue association of exogenous surfactant in preterm newborn rabbits.","volume":"57","author":"Bohlin","year":"2005","journal-title":"Pediatr Res"},{"key":"poi230078r31","author":"Kattwinkel","year":"2004"},{"key":"poi230078r32","year":"2018"},{"issue":"3","key":"poi230078r33","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008311.pub2","article-title":"Pharyngeal instillation of surfactant before the first breath for prevention of morbidity and mortality in preterm infants at risk of respiratory distress syndrome.","author":"Abdel-Latif","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"issue":"7","key":"poi230078r34","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-035994","article-title":"Study protocol for the POPART study\u2014Prophylactic Oropharyngeal Surfactant for Preterm Infants: A Randomised Trial.","volume":"10","author":"Murphy","year":"2020","journal-title":"BMJ Open"},{"key":"poi230078r35","doi-asserted-by":"publisher","first-page":"c332","DOI":"10.1136\/bmj.c332","article-title":"CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials.","volume":"340","author":"Schulz","year":"2010","journal-title":"BMJ"},{"issue":"18","key":"poi230078r36","doi-asserted-by":"publisher","first-page":"S543","DOI":"10.1161\/CIR.0000000000000267","article-title":"Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.","volume":"132","author":"Wyckoff","year":"2015","journal-title":"Circulation"},{"key":"poi230078r37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap Consortium: building an international community of software platform partners.","volume":"95","author":"Harris","year":"2019","journal-title":"J Biomed Inform"},{"issue":"1","key":"poi230078r38","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12874-017-0442-1","article-title":"When and how should multiple imputation be used for handling missing data in randomised clinical trials\u2014a practical guide with flowcharts.","volume":"17","author":"Jakobsen","year":"2017","journal-title":"BMC Med Res Methodol"},{"issue":"12","key":"poi230078r39","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1001\/jama.2019.1660","article-title":"Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial.","volume":"321","author":"Kirpalani","year":"2019","journal-title":"JAMA"},{"issue":"9","key":"poi230078r40","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1001\/jamapediatrics.2021.1497","article-title":"Comparison of respiratory support after delivery in infants born before 28 weeks\u2019 gestational age: the CORSAD randomized clinical trial.","volume":"175","author":"Donaldsson","year":"2021","journal-title":"JAMA Pediatr"}],"container-title":["JAMA Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/articlepdf\/2812571\/jamapediatrics_murphy_2023_oi_230078_1706643582.69182.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T16:06:46Z","timestamp":1707149206000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/fullarticle\/2812571"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2024,2,1]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapediatrics.2023.5082","relation":{},"ISSN":["2168-6203"],"issn-type":[{"value":"2168-6203","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2,1]]}}}