{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:12:23Z","timestamp":1792541543393,"version":"4.5.0"},"reference-count":19,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Premature infants are often referred for the definitive procedural closure of the patent ductus arteriosus (PDA) with the failure of, or contraindication to, pharmacotherapy and the inability to wean respiratory support. However, once this need is identified, the importance of expedited closure is unclear. The objective of this study was to compare the effect of the timing of definitive closure (i.e., surgical ligation or device occlusion) on early respiratory outcomes in premature infants. Method: We first specify a hypothetical randomized trial (the \u201ctarget trial\u201d) that would estimate the effect on extubation of early (0\u20134 days from referral) vs. late (5\u201314 days from referral) definitive PDA closure. We then emulate this target trial using a single-institution registry of premature infants (born &lt;30 weeks or with a birth weight &lt; 1500 g) who underwent the definitive closure of PDA between January 2014 and October 2023. Results: We identify 131 eligible infants. At the end of the follow-up, 70 and 38 infants were adherent to early and late PDA closure strategies, respectively. The cumulative incidence of extubation in the early group was higher than that in the late group until day 40 (maximum risk difference: 22 percentage points at day 13; 95% CI: \u221211 to 56). Outcomes were similar at the end of the 45-day follow-up period (risk difference: \u22121 percentage point; 95% CI: \u221246 to 42). Conclusions: The need for mechanical ventilation was equivalent between early and late PDA closure strategies at the end of a 45-day follow-up period although infants in the early intervention group were extubated sooner.<\/jats:p>","DOI":"10.3390\/jcm14062072","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T10:43:51Z","timestamp":1742294631000},"page":"2072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effect on Extubation of Early vs. Late Definitive Closure of the Patent Ductus Arteriosus in Premature Infants: A Target Trial Emulation Using Electronic Health Records"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhou","family":"Du","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5384-3472","authenticated-orcid":false,"given":"Craig R.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Departments of Respiratory Care & Extracorporeal Membrane Oxygenation, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8116","authenticated-orcid":false,"given":"Michael","family":"Farias","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Porras","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5103-5834","authenticated-orcid":false,"given":"Philip T.","family":"Levy","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1258-7278","authenticated-orcid":false,"given":"Arin L.","family":"Madenci","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Surgery, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.athoracsur.2005.03.141","article-title":"Consequences of Delayed Surgical Closure of Patent Ductus Arteriosus in Very Premature Infants","volume":"81","author":"Jaillard","year":"2006","journal-title":"Ann. Thorac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.5090\/kjtcs.2014.47.5.444","article-title":"Surgical Ligation on Significant Patent Ductus Arteriosus in Very Low Birth Weight Infants: Comparison between Early and Late Ligations","volume":"47","author":"Lee","year":"2014","journal-title":"Korean J. Thorac. Cardiovasc. 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Ann."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e19356","DOI":"10.1097\/MD.0000000000019356","article-title":"The Optimal Timing of Surgical Ligation of Patent Ductus Arteriosus in Preterm or Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis","volume":"99","author":"Yan","year":"2020","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1164\/rccm.202310-1733OC","article-title":"Patent Ductus Arteriosus and Lung Magnetic Resonance Imaging Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension","volume":"210","author":"Bjorkman","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1164\/rccm.202203-0570OC","article-title":"Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension","volume":"207","author":"Gentle","year":"2023","journal-title":"Am. 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Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3346\/jkms.2014.29.4.581","article-title":"The Timing of Surgical Ligation for Patent Ductus Arteriosus Is Associated with Neonatal Morbidity in Extremely Preterm Infants Born at 23\u201325 Weeks of Gestation","volume":"29","author":"Sung","year":"2014","journal-title":"J. Korean Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s00431-021-04004-3","article-title":"Ductal Ligation Timing and Neonatal Outcomes: A 12-Year Bicentric Comparison","volume":"180","author":"Martini","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113716","DOI":"10.1016\/j.jpeds.2023.113716","article-title":"Trends in Procedural Closure of the Patent Ductus Arteriosus among Infants Born at 22 to 30 Weeks\u2019 Gestation","volume":"263","author":"Shah","year":"2023","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113712","DOI":"10.1016\/j.jpeds.2023.113712","article-title":"Current Trends in Invasive Closure of Patent Ductus Arteriosus in Very Low Birth Weight Infants in United States Children\u2019s Hospitals, 2016\u20132021","volume":"263","author":"Lai","year":"2023","journal-title":"J Pediatr"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F124","DOI":"10.1136\/archdischild-2013-304896","article-title":"Definitions of Extubation Success in Very Premature Infants: A Systematic Review","volume":"99","author":"Giaccone","year":"2014","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/s41390-021-01475-w","article-title":"Patent Ductus Arteriosus, Tracheal Ventilation, and the Risk of Bronchopulmonary Dysplasia","volume":"91","author":"Clyman","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/s41372-019-0496-5","article-title":"Duration of Significant Patent Ductus Arteriosus and Bronchopulmonary Dysplasia in Extremely Preterm Infants","volume":"39","author":"Mirza","year":"2019","journal-title":"J. Perinatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1055\/s-0039-1697672","article-title":"Relationship between Duration of Infant Exposure to a Moderate-to-Large Patent Ductus Arteriosus Shunt and the Risk of Developing Bronchopulmonary Dysplasia or Death Before 36 Weeks","volume":"37","author":"Clyman","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/s41372-020-0718-x","article-title":"The Effect of Prolonged Tracheal Intubation on the Association between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia (Grades 2 and 3)","volume":"40","author":"Clyman","year":"2020","journal-title":"J. Perinatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:01Z","timestamp":1760028961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":19,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14062072"],"URL":"https:\/\/doi.org\/10.3390\/jcm14062072","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}