{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:47:47Z","timestamp":1785534467017,"version":"3.56.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001104","name":"RANZCOG Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Infants with congenital diaphragmatic hernia (CDH) are predisposed to pulmonary hypertension after birth, owing to lung hypoplasia that impairs fetal pulmonary vascular development. Antenatal sildenafil treatment attenuates abnormal pulmonary vascular and alveolar development in rabbit and rodent CDH models, but whether this translates to functional improvements after birth remains unknown. We aimed to evaluate the effect of antenatal sildenafil on neonatal pulmonary hemodynamics and lung function in lambs with diaphragmatic hernia (DH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DH was surgically induced at approximately 80\u2009days' gestation in 16 lamb fetuses (term in lambs is approximately 147\u2009days). From 105\u2009days' gestation, ewes received either sildenafil (0.21\u2009mg\/kg\/h intravenously) or saline infusion until delivery (<jats:italic>n<\/jats:italic>\u2009=\u20098 fetuses in each group). At approximately 138\u2009days' gestation, all lambs were instrumented and then delivered via Cesarean section. The lambs were ventilated for 120\u2009min with continuous recording of physiological (pulmonary and carotid artery blood flow and pressure; cerebral oxygenation) and ventilatory parameters, and regular assessment of arterial blood gas tensions. Only lambs that survived until delivery and with a confirmed diaphragmatic defect at postmortem examination were included in the analysis; these comprised six DH\u2010sildenafil lambs and six DH\u2010saline control lambs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lung\u2010to\u2010body\u2010weight ratio (0.016\u2009\u00b1\u20090.001 <jats:italic>vs<\/jats:italic> 0.013\u2009\u00b1\u20090.001; <jats:italic>P<\/jats:italic>\u2009=\u20090.06) and dynamic lung compliance (0.8\u2009\u00b1\u20090.2 <jats:italic>vs<\/jats:italic> 0.7\u2009\u00b1\u20090.2\u2009mL\/cmH<jats:sub>2<\/jats:sub>O; <jats:italic>P<\/jats:italic>\u2009=\u20090.72) were similar in DH\u2010sildenafil lambs and controls. Pulmonary vascular resistance decreased following lung aeration to a greater degree in DH\u2010sildenafil lambs, and was 4\u2010fold lower by 120\u2009min after cord clamping than in controls (0.6\u2009\u00b1\u20090.1 <jats:italic>vs<\/jats:italic> 2.2\u2009\u00b1\u20090.6\u2009mmHg\/(mL\/min); <jats:italic>P<\/jats:italic>\u2009=\u20090.002). Pulmonary arterial pressure was also lower (46\u2009\u00b1\u20092 <jats:italic>vs<\/jats:italic> 59\u2009\u00b1\u20092\u2009mmHg; <jats:italic>P<\/jats:italic>\u2009=\u20090.048) and pulmonary blood flow higher (25\u2009\u00b1\u20093 <jats:italic>vs<\/jats:italic> 8\u2009\u00b1\u20092\u2009mL\/min\/kg; <jats:italic>P<\/jats:italic>\u2009=\u20090.02) in DH\u2010sildenafil than in DH\u2010saline lambs at 120\u2009min. Throughout the 120\u2010min ventilation period, the partial pressure of arterial carbon dioxide tended to be lower in DH\u2010sildenafil lambs than in controls (63\u2009\u00b1\u20098 <jats:italic>vs<\/jats:italic> 87\u2009\u00b1\u20098\u2009mmHg; <jats:italic>P<\/jats:italic>\u2009=\u20090.057), and there was no significant difference in partial pressure of arterial oxygen between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sustained maternal antenatal sildenafil infusion reduced pulmonary arterial pressure and increased pulmonary blood flow in DH lambs for the first 120\u2009min after birth. These findings of improved pulmonary vascular function are consistent with improved pulmonary vascular structure seen in two previous animal models. The data support the rationale for a clinical trial investigating the effect of antenatal sildenafil in reducing the risk of neonatal pulmonary hypertension in infants with CDH. Copyright \u00a9 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.20415","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T08:54:00Z","timestamp":1564563240000},"page":"506-516","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Antenatal sildenafil treatment improves neonatal pulmonary hemodynamics and gas exchange in lambs with diaphragmatic hernia"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3587-0535","authenticated-orcid":false,"given":"A. J.","family":"Kashyap","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. L. J.","family":"Dekoninck","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Erasmus MC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A.","family":"Rodgers","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Thio","sequence":"additional","affiliation":[{"name":"Newborn Research Centre, The Royal Women's Hospital  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology The University of Melbourne  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.\u2009V.","family":"Mcgillick","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. J.","family":"Amberg","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Skinner","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Moxham","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5029-7899","authenticated-orcid":false,"given":"F. M.","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Division of Woman and Child University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4920-945X","authenticated-orcid":false,"given":"J. A.","family":"Deprest","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Division of Woman and Child University Hospitals Leuven  Leuven Belgium"},{"name":"Institute for Women's Health, University College London Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. B.","family":"Hooper","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. J.","family":"Crossley","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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