{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:34:49Z","timestamp":1780504489043,"version":"3.54.1"},"reference-count":39,"publisher":"Cambridge University Press (CUP)","issue":"6","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Cardiol Young"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1047951123004456_as1\"><jats:title>Background:<\/jats:title><jats:p>Persistent pulmonary hypertension of the newborn is a life-threatening condition that affects about 1\u20132 per 1,000 live births worldwide. Bosentan is an oral dual endothelin receptor antagonist that may have a beneficial effect on persistent pulmonary hypertension of the newborn by reducing pulmonary vascular resistance and improving oxygenation. However, its role in persistent pulmonary hypertension of the newborn remains unclear.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123004456_as2\"><jats:title>Objectives:<\/jats:title><jats:p>To systematically evaluate the efficacy and safety of bosentan as an adjuvant therapy for persistent pulmonary hypertension of the newborn in newborns.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123004456_as3\"><jats:title>Methods:<\/jats:title><jats:p>We searched six English and two Chinese databases from their inception to 1 January 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomised controlled trials and retrospective studies that compared bosentan with placebo or other drugs for persistent pulmonary hypertension of the newborn in newborns. We performed a meta-analysis using random-effects models and assessed the risk of bias and heterogeneity in the included studies.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123004456_as4\"><jats:title>Results:<\/jats:title><jats:p>We included 10 studies with a total of 550 participants. Bosentan significantly reduced the treatment failure rate (relative risk = 0.25, P &lt; 0.001), pulmonary artery pressure (mean difference = \u221211.79, P &lt; 0.001), and length of hospital stay (mean difference = \u22121.04, P = 0.003), and increased the partial pressure of oxygen (mean difference = 10.02, P &lt; 0.001) and blood oxygen saturation (SpO2) (mean difference = 8.24, P &lt; 0.001) compared with a placebo or other drugs. The occurrence of adverse reactions was not significantly different between bosentan and a placebo or other drugs.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123004456_as5\"><jats:title>Conclusions:<\/jats:title><jats:p>Bosentan is effective in the treatment of persistent pulmonary hypertension of the newborn but adverse reactions such as abnormal liver function should be observed when using it.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1047951123004456","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T05:55:43Z","timestamp":1707371743000},"page":"1334-1341","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["Bosentan in the treatment of persistent pulmonary hypertension in newborns: a systematic review and meta-analysis"],"prefix":"10.1017","volume":"34","author":[{"given":"Ning","family":"Gao","sequence":"first","affiliation":[{"name":"Baoding No.1 Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Lv","sequence":"additional","affiliation":[{"name":"Baoding No.1 Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4458-5279","authenticated-orcid":false,"given":"Yanbin","family":"Cui","sequence":"additional","affiliation":[{"name":"Baoding No.3 Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Baoding No.1 Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"Baoding No.1 Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"S1047951123004456_ref22","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/jp.2011.157","article-title":"A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn","volume":"32","author":"Mohamed","year":"2012","journal-title":"J Perinatol"},{"key":"S1047951123004456_ref10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1161\/CIRCULATIONAHA.110.016667","article-title":"A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension","volume":"125","author":"Barst","year":"2012","journal-title":"Circulation"},{"key":"S1047951123004456_ref13","doi-asserted-by":"crossref","first-page":"L755","DOI":"10.1152\/ajplung.00138.2010","article-title":"Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension","volume":"301","author":"Chester","year":"2011","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"S1047951123004456_ref25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4103\/jcn.JCN_5_20","article-title":"Comparison of the effects of bosentan and sildenafil in the treatment of persistent pulmonary arterial hypertension in infants","volume":"9","author":"Farhangdoust","year":"2020","journal-title":"J Clin Neonatol"},{"key":"S1047951123004456_ref16","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1007\/s00134-003-2016-4","article-title":"Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery","volume":"29","author":"Stocker","year":"2003","journal-title":"Intensive Care Med"},{"key":"S1047951123004456_ref35","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00431-007-0531-y","article-title":"Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan","volume":"167","author":"Goissen","year":"2008","journal-title":"Eur J Pediatr"},{"key":"S1047951123004456_ref37","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s00431-011-1422-9","article-title":"Combination therapy for life-threatening pulmonary hypertension in a premature infant: first report on bosentan use","volume":"170","author":"Radicioni","year":"2011","journal-title":"Eur J Pediatr"},{"key":"S1047951123004456_ref4","first-page":"H875","article-title":"Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation","volume":"263","author":"Kinsella","year":"1992","journal-title":"Am J Physiol"},{"key":"S1047951123004456_ref24","first-page":"333","article-title":"Comparison of the efficacy of sildenafil alone versus sildenafil plus bosentan in newborns with persistent pulmonary hypertension","volume":"30","author":"Fatima","year":"2018","journal-title":"J Ayub Med Coll Abbottabad"},{"key":"S1047951123004456_ref2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jpeds.2016.06.078","article-title":"Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: results of the randomized multicenter placebo-controlled exploratory trial","volume":"177","author":"Steinhorn","year":"2016","journal-title":"J Pediatr"},{"key":"S1047951123004456_ref23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pedneo.2017.02.003","article-title":"Effect of bosentan therapy in persistent pulmonary hypertension of the newborn","volume":"59","author":"Maneenil","year":"2018","journal-title":"Pediatr Neonatol"},{"key":"S1047951123004456_ref29","first-page":"53","article-title":"Efficacy and safety of bosentan combined with milrinone in the treatment of persistent pulmonary hypertension of the newborn","volume":"25","author":"Li","year":"2021","journal-title":"Med Forum"},{"key":"S1047951123004456_ref33","first-page":"3096","article-title":"Observation on the effect of high-frequency oscillatory ventilation combined with milrinone on persistent pulmonary hypertension of the newborn","volume":"30","author":"Li","year":"2015","journal-title":"Maternal Child Health Care China"},{"key":"S1047951123004456_ref34","first-page":"1073","article-title":"Long-term outcome of bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart diseases","volume":"47","author":"Zhang","year":"2019","journal-title":"Clin J Med Officers"},{"key":"S1047951123004456_ref39","doi-asserted-by":"crossref","first-page":"L361","DOI":"10.1152\/ajplung.00277.2013","article-title":"Endothelin-1 decreases endothelial PPAR\u03b3 signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension","volume":"306","author":"Wolf","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"S1047951123004456_ref3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1164\/rccm.201409-1594OC","article-title":"Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia","volume":"191","author":"Mourani","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"S1047951123004456_ref7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jpeds.2008.09.021","article-title":"Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease","volume":"154","author":"Mourani","year":"2009","journal-title":"J Pediatr"},{"key":"S1047951123004456_ref11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000088192","article-title":"Neonatal persistent pulmonary hypertension treated with milrinone: four case reports","volume":"89","author":"Bassler","year":"2006","journal-title":"Biol Neonate"},{"key":"S1047951123004456_ref14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMoa060442","article-title":"Early inhaled nitric oxide therapy in premature newborns with respiratory failure","volume":"355","author":"Kinsella","year":"2006","journal-title":"N Engl J Med"},{"key":"S1047951123004456_ref20","unstructured":"20. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions:version 5.1.0 (updated February). The Cochrane Collaboration, 2011. http:\/\/www.cochrane-handbook.org."},{"key":"S1047951123004456_ref1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1164\/rccm.201210-1928PP","article-title":"Implications of the U.S. food and drug administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension","volume":"187","author":"Abman","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"S1047951123004456_ref15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1053\/j.semperi.2005.04.008","article-title":"Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension","volume":"29","author":"Kinsella","year":"2005","journal-title":"Semin Perinatol"},{"key":"S1047951123004456_ref19","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1161\/CIR.0000000000000329","article-title":"Pediatric pulmonary hypertension: guidelines from the American heart association and American thoracic society","volume":"132","author":"Abman","year":"2015","journal-title":"Circulation"},{"key":"S1047951123004456_ref28","first-page":"111","article-title":"Efficacy and safety of bosentan combined with milrinone in the treatment of persistent pulmonary hypertension of the newborn","volume":"33","author":"Li","year":"2020","journal-title":"J Med Theory Pract"},{"key":"S1047951123004456_ref21","unstructured":"21. Wells A, Shea B, O\u2019Connell D, et al. Thenewcastle-ottawa scale (NOS) for assessing the quality of nonrandomisedstudies in meta-analyses. [EB\/OL]. (2012-06-15)[2014-01-13]. http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm."},{"key":"S1047951123004456_ref8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.106.630715","article-title":"Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study","volume":"114","author":"Gali\u00e8","year":"2006","journal-title":"Circulation"},{"key":"S1047951123004456_ref30","first-page":"1","article-title":"Effects of bosentan combined with treprostinil on red blood cell distribution width and serum melatonin in neonates with persistent pulmonary hypertension","volume":"27","author":"Wang","year":"2021","journal-title":"J Pediatr Pharm"},{"key":"S1047951123004456_ref36","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1111\/j.1651-2227.2009.01386.x","article-title":"Successful treatment of persistent pulmonary hypertension of the newborn with bosentan","volume":"98","author":"Nakwan","year":"2009","journal-title":"Acta Paediatr"},{"key":"S1047951123004456_ref18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.hfc.2012.04.012","article-title":"Pharmacotherapy for pulmonary arterial hypertension","volume":"8","author":"Ramani","year":"2012","journal-title":"Heart Fail Clin"},{"key":"S1047951123004456_ref38","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1183\/09031936.00138706","article-title":"Results of european post-marketing surveillance of bosentan in pulmonary hypertension","volume":"30","author":"Humbert","year":"2007","journal-title":"Eur Respir J"},{"key":"S1047951123004456_ref6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jpeds.2007.11.006","article-title":"Left ventricular diastolic dysfunction in bronchopulmonary dysplasia","volume":"152","author":"Mourani","year":"2008","journal-title":"J Pediatr"},{"key":"S1047951123004456_ref5","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJM199306173282402","article-title":"Expression of endothelin-1 in the lungs of patients with pulmonary hypertension","volume":"328","author":"Giaid","year":"1993","journal-title":"N Engl J Med"},{"key":"S1047951123004456_ref31","first-page":"56","article-title":"Clinical observation of bosentan in the treatment of infants with congenital heart disease combined with pulmonary hypertension","volume":"54","author":"Pan","year":"2016","journal-title":"J Shandong University"},{"key":"S1047951123004456_ref26","first-page":"216","article-title":"Efficacy, safety and tolerability of bosentan as an adjuvant to sildenafil and sildenafil alone in persistant pulmonary hypertension of newborn (PPHN)","volume":"11","author":"Vijay Kumar","year":"20216","journal-title":"Interv Med Appl Sci"},{"key":"S1047951123004456_ref27","first-page":"2390","article-title":"Therapeutic effect of bosentan and levocarnitine combined with sildenafil on pulmonary hypertension of the newborn","volume":"30","author":"Wang","year":"2019","journal-title":"Hainan Med J"},{"key":"S1047951123004456_ref9","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2","volume":"117","author":"Gali\u00e8","year":"2008","journal-title":"Circulation"},{"key":"S1047951123004456_ref17","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/lt.20459","article-title":"Hemodynamics and survival of patients with portopulmonary hypertension","volume":"11","author":"Kawut","year":"2005","journal-title":"Liver Transpl"},{"key":"S1047951123004456_ref12","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1542\/peds.2007-0726","article-title":"Inhaled nitric oxide for preterm infants: a systematic review","volume":"120","author":"Barrington","year":"2007","journal-title":"Pediatrics"},{"key":"S1047951123004456_ref32","first-page":"4993","article-title":"Clinical observation of milrinone in the treatment of persistent pulmonary hypertension of newborn","volume":"27","author":"Qian","year":"2016","journal-title":"China Pharm"}],"container-title":["Cardiology in the Young"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1047951123004456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T01:47:11Z","timestamp":1758851231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1047951123004456\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["S1047951123004456"],"URL":"https:\/\/doi.org\/10.1017\/s1047951123004456","relation":{},"ISSN":["1047-9511","1467-1107"],"issn-type":[{"value":"1047-9511","type":"print"},{"value":"1467-1107","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]},"assertion":[{"value":"\u00a9 The Author(s), 2024. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}