{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:31:53Z","timestamp":1787697113726,"version":"build-2784847793"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of bosentan-related therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026 for clinical studies of bosentan in neonates with PPHN (CRD420261338730). Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analysis was performed using RevMan 5.4. Outcomes included treatment failure, change in pulmonary artery pressure, length of hospital stay, duration of mechanical ventilation, absolute tricuspid regurgitation values at 72\u2005h, reduction in tricuspid regurgitation at 72\u2005h, and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine studies were included from 187 identified records. Bosentan-related therapy was associated with a lower treatment failure rate than control treatment (RR: 0.27, 95% CI: 0.14\u20130.51;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.0001). In haemodynamic outcomes, bosentan-related therapy was associated with lower absolute tricuspid regurgitation values at 72\u2005h (MD: \u22129.15, 95% CI: \u221212.79\u2013\u22125.52;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.00001) and greater reduction in tricuspid regurgitation at 72\u2005h (MD: \u22126.42, 95% CI: \u221211.30\u2013\u22121.54;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.01). Reduction in pulmonary artery pressure also favoured bosentan-related therapy, although the difference was of borderline significance (MD: \u22122.69, 95% CI \u22125.40\u20130.01;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.05). By contrast, bosentan-related therapy was not associated with a significant reduction in length of hospital stay (MD: \u22121.06, 95% CI \u22122.38\u20130.27;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.12), and duration of mechanical ventilation was longer in the bosentan-related therapy group (MD: 2.04, 95% CI 1.26\u20132.82;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.00001). Reported adverse events included hypotension, anaemia, oedema, vomiting, and hepatic abnormalities, including elevated liver enzymes or abnormal liver function. However, hepatic safety could not be quantitatively assessed because liver-related adverse events were inconsistently defined and reported across studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bosentan-related therapy may be associated with a lower risk of treatment failure and favorable changes in echocardiography-derived pulmonary pressure estimates in neonates with PPHN. However, current evidence does not support a clear benefit in harder clinical outcomes such as length of hospital stay, and no reduction in duration of mechanical ventilation was observed. Short-term safety appears acceptable, but caution remains warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD420261338730<\/jats:ext-link>\n                      . PROSPERO: CRD420261338730\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1836276","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:06:44Z","timestamp":1780466804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of bosentan-related therapy in neonates with persistent pulmonary hypertension of the newborn: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Guanghong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Huadu District People\u2019s Hospital of Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huadu District People\u2019s Hospital of Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huadu District People\u2019s Hospital of Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huadu District People\u2019s Hospital of Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huadu District People\u2019s Hospital of Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40748-015-0015-4","article-title":"Persistent pulmonary 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