{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:24:27Z","timestamp":1788557067077,"version":"build-2803163510"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"crossref","award":["Project Grant scheme - 201909"],"award-info":[{"award-number":["Project Grant scheme - 201909"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85\u201395% within the first 10\u00a0min. Over the last 10\u00a0years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO<jats:sub>2<\/jats:sub>) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (&lt;\u20090.3), up to moderate concentrations (0.3\u20130.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>An international cluster, cross-over randomized trial of initial FiO<jats:sub>2<\/jats:sub> of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24\u00a0months corrected age will be conducted. Preterm infants born between 23<jats:sup>0\/7<\/jats:sup> and 28<jats:sup>6\/7<\/jats:sup>\u00a0weeks\u2019 gestation will be eligible. Each participating hospital will be randomized to either an initial FiO<jats:sub>2<\/jats:sub> concentration of either 0.3 or 0.6 to recruit for up to 12\u00a0months\u2019 and then crossed over to the other concentration for up to 12\u00a0months. The intervention will be initial FiO<jats:sub>2<\/jats:sub> of 0.6, and the comparator will be initial FiO<jats:sub>2<\/jats:sub> of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24\u00a0months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18\u201324\u00a0months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-024-08080-2","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T14:02:13Z","timestamp":1712239333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18\u201324\u00a0months in very low birthweight infants?"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9798-2415","authenticated-orcid":false,"given":"Georg M.","family":"Schm\u00f6lzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth V.","family":"Asztalos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Beltempo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Boix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Dempsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"El-Naggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil N.","family":"Finer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Anna","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Mukerji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda H. Y.","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryna","family":"Yaskina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakesh S.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Sheta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amuchou","family":"Soraisham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tarnow-Mordi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Vento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"behalf of the HiLo trial collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"8080_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.0004-8666.2002.00119.x","volume":"42","author":"CE East","year":"2002","unstructured":"East CE, Colditz PB, Begg LM, Brennecke SP. 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