{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:45:19Z","timestamp":1789076719200,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>The identification of an optimal management strategy for the patent ductus arteriosus (PDA) in the context of extreme prematurity remains elusive. Observational studies have reported a persistent association between PDA and neonatal adverse outcomes, but by and large, no clinical trial, to date, has demonstrated that treating a PDA results in a reduction of those morbidities. This discrepancy has led many to assume that the PDA is an innocent bystander in the physiological mechanisms responsible for such complications and a reluctance to actively pursue shunt elimination. It would be remiss to discount the volume of evidence available clearly documenting a strong association between longstanding PDA exposure and negative outcomes. There needs to be a radical change in the design, patient selection and possible outcome assessment in any further trials addressing the PDA. The purpose of this review is to explore the reasons that preclude existing clinical trials from definitively ascribing a causal relationship between PDA patency and adverse outcomes in the context of extreme prematurity, why previous studies have failed to demonstrate significant beneficial effects following PDA treatment and how future research may be conducted to allow us to draw concrete conclusions regarding the potential merits of ductal closure.<\/jats:p>","DOI":"10.3390\/children8010047","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T01:33:29Z","timestamp":1610674409000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Patent Ductus Arteriosus Clinical Trials: Lessons Learned and Future Directions"],"prefix":"10.3390","volume":"8","author":[{"given":"Aisling","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Neonatology, The Rotunda Hospital, DO1 P5W9 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-822X","authenticated-orcid":false,"given":"Afif","family":"EL-Khuffash","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Rotunda Hospital, DO1 P5W9 Dublin, Ireland"},{"name":"Department of Paediatrics, The Royal College of Surgeons in Ireland, DO1 P5W9 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1053\/siny.2000.0036","article-title":"The treatment of patent ductus arteriosus in preterm infants. 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