{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:54:09Z","timestamp":1768017249040,"version":"3.49.0"},"reference-count":29,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND AND OBJECTIVES<\/jats:title>\n                  <jats:p>The European Union Nitric Oxide trial was designed to assess the potential benefits of inhaled nitric oxide (iNO) compared with placebo in infants with respiratory failure. This follow-up study evaluated respiratory, neurodevelopmental, and other outcomes for infants entered into the European Union Nitric Oxide trial to age 2 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>In a multicenter, randomized, double-blind study, preterm infants born at &amp;lt;29 weeks\u2019 gestation with moderate respiratory failure were allocated to receive iNO (5 ppm) or placebo for 7 to 21 days. Subjects underwent assessments at 1 and 2 years corrected for prematurity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>At 36 weeks\u2019 postmenstrual age, 696 of 792 infants were alive; 4 in the iNO arm subsequently died before age 2 years compared with 7 in the control arm. We evaluated 95% of the survivors at 12 months and 90% at 2 years. In the iNO arm, 244 of 363 (67.2%) infants had survived without disability at age 2 years compared with 270 of 374 (72.2%) who received placebo (P = .094). Mean (SD) cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) were 94 (13) in the iNO group and 95 (14) in the placebo group; in the iNO group, 19% scored &amp;lt;85 and 9.5% developed cerebral palsy compared with 13.3% and 9%, respectively. There were no significant differences in hospitalizations overall or due to respiratory illness in use of home oxygen therapy or respiratory medications, in growth, or in other health outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>At 2 years of age, low-dose (5 ppm) iNO started early (&amp;lt;24 hours after birth) for a median of 20 days did not affect neurodevelopmental or other health outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2013-0007","type":"journal-article","created":{"date-parts":[[2013,8,13]],"date-time":"2013-08-13T00:25:48Z","timestamp":1376353548000},"page":"e695-e703","source":"Crossref","is-referenced-by-count":17,"title":["Two-Year Outcomes of a Randomized Controlled Trial of Inhaled Nitric Oxide in Premature Infants"],"prefix":"10.1542","volume":"132","author":[{"given":"Xavier","family":"Durrmeyer","sequence":"first","affiliation":[{"name":"Department of Neonatology, CRC, Centre Hospitalier Intercommunal de Cr\u00e9teil, Cr\u00e9teil, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Hummler","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital, University of Ulm, Ulm, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Sanchez-Luna","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Hospital Universitario Gregorio Mara\u00f1on, Madrid, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virgilio P.","family":"Carnielli","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Clinical Sciences, Polytechnic University of Marche and Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Field","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Greenough","sequence":"additional","affiliation":[{"name":"Division of Asthma, Allergy and Lung Biology, King\u2019s College, London, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Van Overmeire","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Antwerp University Hospital, Antwerp, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baldvin","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Karolinska Institute, Stockholm, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikko","family":"Hallman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Christophe","family":"Mercier","sequence":"additional","affiliation":[{"name":"H\u00f4pital Robert Debr\u00e9, Paris, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Marlow","sequence":"additional","affiliation":[{"name":"Institute for Women's Health, University College London, London, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Baldassarre","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Ikaria, Inc, Hampton, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"issue":"9608","key":"2021120902564327000_B1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0140-6736(08)60136-1","article-title":"An overview of mortality and sequelae of preterm birth from infancy to adulthood.","volume":"371","author":"Saigal","year":"2008","journal-title":"Lancet"},{"issue":"6","key":"2021120902564327000_B2","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.jpeds.2005.01.047","article-title":"Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes.","volume":"146","author":"Walsh","year":"2005","journal-title":"J Pediatr"},{"issue":"5","key":"2021120902564327000_B3","doi-asserted-by":"crossref","first-page":"e359","DOI":"10.1542\/peds.112.5.e359","article-title":"Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes.","volume":"112","author":"Short","year":"2003","journal-title":"Pediatrics"},{"issue":"2","key":"2021120902564327000_B4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.siny.2012.01.009","article-title":"Long term respiratory outcomes of very premature birth (&lt;32 weeks).","volume":"17","author":"Greenough","year":"2012","journal-title":"Semin Fetal Neonatal Med"},{"issue":"1","key":"2021120902564327000_B5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa043514","article-title":"Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.","volume":"353","author":"Mestan","year":"2005","journal-title":"N Engl J Med"},{"issue":"1","key":"2021120902564327000_B6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jpeds.2007.03.017","article-title":"Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide.","volume":"151","author":"Hintz","year":"2007","journal-title":"J Pediatr"},{"issue":"4","key":"2021120902564327000_B7","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jpeds.2009.10.011","article-title":"Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide.","volume":"156","author":"Walsh","year":"2010","journal-title":"J Pediatr"},{"issue":"9738","key":"2021120902564327000_B8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0140-6736(10)60664-2","article-title":"Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial.","volume":"376","author":"Mercier","year":"2010","journal-title":"Lancet"},{"issue":"3","key":"2021120902564327000_B9","doi-asserted-by":"crossref","first-page":"L450","DOI":"10.1152\/ajplung.00347.2004","article-title":"Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease.","volume":"288","author":"McCurnin","year":"2005","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"6","key":"2021120902564327000_B10","doi-asserted-by":"crossref","first-page":"e10916","DOI":"10.1371\/journal.pone.0010916","article-title":"Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat.","volume":"5","author":"Pansiot","year":"2010","journal-title":"PLoS ONE"},{"key":"2021120902564327000_B11","unstructured":"Centers for Disease Control and Prevention, National Center for Health Statistics. 2000 CDC growth charts for the United States: methods and development. Available at: www.cdc.gov\/nchs\/data\/series\/sr_11\/sr11_246.pdf. Accessed June 21, 2011"},{"issue":"10","key":"2021120902564327000_B12","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1469-8749.2008.03089.x","article-title":"Content validity of the expanded and revised Gross Motor Function Classification System.","volume":"50","author":"Palisano","year":"2008","journal-title":"Dev Med Child Neurol"},{"issue":"12","key":"2021120902564327000_B13","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1017\/S001216220600209X","article-title":"Reliability of the manual ability classification system for children with cerebral palsy.","volume":"48","author":"Morris","year":"2006","journal-title":"Dev Med Child Neurol"},{"key":"2021120902564327000_B14","volume-title":"Bayley Scales of Infant and Toddler Development, Technical Manual","author":"Bayley","year":"2005","edition":"3rd ed."},{"key":"2021120902564327000_B15","unstructured":"British Association of Perinatal Medicine. Classification of health status at 2 years as a perinatal outcome. Version 1.0. Report of a BAPM\/RCPCH Working Group. Available at: www.bapm.org\/publications\/documents\/guidelines\/Outcome_BAPM_WG_report_v6_Jan08.pdf. Accessed November 30, 2012"},{"issue":"10","key":"2021120902564327000_B16","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/sj.jp.7211801","article-title":"Cost, causes and rates of rehospitalization of preterm infants.","volume":"27","author":"Underwood","year":"2007","journal-title":"J Perinatol"},{"issue":"2","key":"2021120902564327000_B17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/WCO.0b013e3282f88bb4","article-title":"Neurodevelopmental outcomes of preterm infants.","volume":"21","author":"Allen","year":"2008","journal-title":"Curr Opin Neurol"},{"issue":"1","key":"2021120902564327000_B18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1552-6909.1995.tb02377.x","article-title":"Problems of preterm infants after discharge.","volume":"24","author":"Blackburn","year":"1995","journal-title":"J Obstet Gynecol Neonatal Nurs"},{"issue":"2","key":"2021120902564327000_B19","doi-asserted-by":"crossref","first-page":"e287","DOI":"10.1542\/peds.2007-3657","article-title":"Reduced exercise capacity in children born very preterm.","volume":"122","author":"Smith","year":"2008","journal-title":"Pediatrics"},{"issue":"2","key":"2021120902564327000_B20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1164\/rccm.200912-1806OC","article-title":"Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study.","volume":"182","author":"Fawke","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2021120902564327000_B21","unstructured":"US Department of Health and Human Services. Healthy People 2010: Volume I\u2013Understanding and Improving Health; Volume II\u2013Objectives for Improving Health. Available at: www.healthypeople.gov\/2010\/Publications. Accessed July 2, 2013"},{"key":"2021120902564327000_B22","first-page":"1","year":"2012"},{"issue":"3","key":"2021120902564327000_B23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1542\/peds.2009-2959","article-title":"Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.","volume":"126","author":"Stoll","year":"2010","journal-title":"Pediatrics"},{"issue":"2","key":"2021120902564327000_B24","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1542\/peds.2010-3507","article-title":"NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants.","volume":"127","author":"Cole","year":"2011","journal-title":"Pediatrics"},{"issue":"4","key":"2021120902564327000_B25","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1542\/peds.2010-2725","article-title":"Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials.","volume":"128","author":"Askie","year":"2011","journal-title":"Pediatrics"},{"issue":"5","key":"2021120902564327000_B26","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1542\/peds.2009-0114","article-title":"Clinical and economic effects of iNO in premature newborns with respiratory failure at 1 year.","volume":"124","author":"Watson","year":"2009","journal-title":"Pediatrics"},{"issue":"8","key":"2021120902564327000_B27","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1097\/NEN.0b013e3181ea5203","article-title":"Nitric oxide plays a key role in myelination in the developing brain.","volume":"69","author":"Olivier","year":"2010","journal-title":"J Neuropathol Exp Neurol"},{"issue":"8","key":"2021120902564327000_B28","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1164\/ajrccm.185.8.897","article-title":"Inhaled NO protects cerebral white matter in neonatal rats with combined brain and lung injury.","volume":"185","author":"Pham","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"2021120902564327000_B29","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1001\/archpediatrics.2010.20","article-title":"Underestimation of developmental delay by the new Bayley-III scale.","volume":"164","author":"Anderson","year":"2010","journal-title":"Arch Pediatr Adolesc Med"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/132\/3\/e695\/1091279\/peds_2013-0007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/132\/3\/e695\/1091279\/peds_2013-0007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T16:16:32Z","timestamp":1639066592000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/132\/3\/e695\/31570\/Two-Year-Outcomes-of-a-Randomized-Controlled-Trial"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,1]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,9,1]]},"published-print":{"date-parts":[[2013,9,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2013-0007","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,1]]}}}