{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:35:56Z","timestamp":1770820556587,"version":"3.50.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012940","name":"Universit\u00e4tsklinikum T\u00fcbingen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012940","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>Extremely low gestational age neonates (ELGANs, i.e. those born before 28 weeks postmenstrual age (PMA)) often require supplemental oxygen and frequently experience intermittent hypo- and hyperoxemic episodes. Exposure to episodes with inadequate oxygen concentrations has been shown to be associated with an increased risk of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI) and death. Closed-loop automatic control of the inspiratory fraction of oxygen (FiO<jats:sub>2<\/jats:sub>-C) reduces number and duration of hypo- and hyperoxemic episodes in ELGANs. Its impacts on clinically important short- and long-term outcomes such as ROP, BPD, NEC, NDI and mortality have not yet been studied.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>An outcome-assessor-blinded, multicentre, randomized-controlled, parallel-group trial for superiority was designed to study the effects of FiO<jats:sub>2<\/jats:sub>-C (provided by standard infant ventilators) in addition to routine manual control (RMC) during respiratory support, compared to RMC only, on short- and long-term clinical outcomes in ELGANs. Two co-primary composite outcomes were defined: (i) death, severe ROP, BPD or NEC, assessed at 36\u2009weeks PMA or, in case of ROP, until complete vascularization of the retina; (ii) death or NDI (defined as language\/cognitive delay, motor impairment, severe visual impairment or hearing impairment), assessed at 2 years corrected age.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Primary outcomes will be compared between the two intervention groups using a Cochran-Mantel-Haenszel test. The factors considered for randomization (centre, sex and gestational age at birth (&lt;\u200926 weeks and\u2009\u2265\u200926 weeks)) will be used to define strata. Results will be presented as adjusted odds ratios with two-sided 95% and 97.5% confidence intervals and two-sided <jats:italic>p<\/jats:italic> values.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The statistical analyses for the FiO<jats:sub>2<\/jats:sub>-C trial were defined in the study protocol and specified in detail in this statistical analysis plan published prior to any statistical analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT03168516. Registered on May 30, 2017.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-024-08615-7","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T15:53:15Z","timestamp":1731426795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Statistical analysis plan for the FiO2-C trial: effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcomes of extremely preterm infants\u2014a randomized-controlled parallel group multicentre trial for safety and efficacy"],"prefix":"10.1186","volume":"25","author":[{"given":"Jochem","family":"K\u00f6nig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Stauch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Engel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Urschitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel R.","family":"Franz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the FiO2-C study group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian F.","family":"Poets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Hummler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik J.","family":"Niemarkt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Bassler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian A.","family":"Maiwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Eichhorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Raubuch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Roth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Schuler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"R\u00f6tsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruimiao","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Kapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M. K.","family":"V\u00f6lkl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibylle C.","family":"Horsinka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmondo N. L.","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"von Buch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Thorsten","family":"K\u00f6rner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birte","family":"Tr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"R\u00fcdiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Seipolt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Mense","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hoehn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Lohmeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-J\u00f6rg","family":"Bittrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Roefke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Niethammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Raecke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Klotz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Koluch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Idel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"L\u00fcbking","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Bohnhorst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Peter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Jacobi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Gille","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Beedgen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Heinzmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"K\u00fchr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Holz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Welcker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich H.","family":"Thome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin W.","family":"Ackermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Gebauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas W.","family":"Flemmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Herber-Jonat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelheid","family":"Kley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Reber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Brickmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kilian","family":"Ackermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Sandk\u00f6tter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Masjosthusmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schroth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Grillh\u00f6sl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Kittel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Michel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Christoph","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Martin","family":"Lode","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel T.","family":"Bosk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-J\u00fcrgen","family":"Gausepohl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Vochem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Strahleck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Neuberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian A.","family":"Maiwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Arand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Ehrhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc R.","family":"Mendler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Essers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Bender","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narmina","family":"Mammodova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Rauch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Bernbeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik J.","family":"Niemarkt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thilo","family":"Mohns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle E. M.","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrica L. M.","family":"van Straaten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"H\u00fctten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"van Westering-Kroon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vrinda","family":"Nair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"issue":"20","key":"8615_CR1","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1001\/jama.2013.5555","volume":"309","author":"B Schmidt","year":"2013","unstructured":"Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, et al. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013;309(20):2111\u201320.","journal-title":"JAMA"},{"issue":"6","key":"8615_CR2","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1001\/jama.2020.10690","volume":"324","author":"AR Franz","year":"2020","unstructured":"Franz AR, Engel C, Bassler D, Rudiger M, Thome UH, Maier RF, et al. Effects of liberal vs restrictive transfusion thresholds on survival and neurocognitive outcomes in extremely low-birth-weight infants: the ETTNO randomized clinical trial. JAMA. 2020;324(6):560\u201370.","journal-title":"JAMA"},{"issue":"3","key":"8615_CR3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1056\/NEJMoa1907423","volume":"382","author":"SE Juul","year":"2020","unstructured":"Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, Robinson T, et al. A randomized trial of erythropoietin for neuroprotection in preterm infants. N Engl J Med. 2020;382(3):233\u201343.","journal-title":"N Engl J Med"},{"issue":"16","key":"8615_CR4","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1056\/NEJMoa2207554","volume":"388","author":"ML Hansen","year":"2023","unstructured":"Hansen ML, Pellicer A, Hyttel-Sorensen S, Ergenekon E, Szczapa T, Hagmann C, et al. Cerebral oximetry monitoring in extremely preterm infants. N Engl J Med. 2023;388(16):1501\u201311.","journal-title":"N Engl J Med"},{"issue":"27","key":"8615_CR5","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1056\/NEJMoa2020248","volume":"383","author":"H Kirpalani","year":"2020","unstructured":"Kirpalani H, Bell EF, Hintz SR, Tan S, Schmidt B, Chaudhary AS, et al. Higher or lower hemoglobin transfusion thresholds for preterm infants. N Engl J Med. 2020;383(27):2639\u201351.","journal-title":"N Engl J Med"},{"issue":"7","key":"8615_CR6","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1056\/NEJMsa0806033","volume":"362","author":"WA Carlo","year":"2010","unstructured":"Carlo WA, Goudar SS, Jehan I, Chomba E, Tshefu A, Garces A, et al. Newborn-care training and perinatal mortality in developing countries. N Engl J Med. 2010;362(7):614\u201323.","journal-title":"N Engl J Med"},{"issue":"22","key":"8615_CR7","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1056\/NEJMoa1302298","volume":"368","author":"BJ Stenson","year":"2013","unstructured":"Group BIUKC, Group BIAC, Group BINZC, Stenson BJ, Tarnow-Mordi WO, Darlow BA, Group BIUKC, Group BIAC, Group BINZC, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med. 2013;368(22):2094\u2013104.","journal-title":"N Engl J Med"},{"issue":"1","key":"8615_CR8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jpeds.2014.01.017","volume":"165","author":"BA Darlow","year":"2014","unstructured":"Darlow BA, Marschner SL, Donoghoe M, Battin MR, Broadbent RS, Elder MJ, et al. Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes. J Pediatr. 2014;165(1):30-5 e2.","journal-title":"J Pediatr."},{"issue":"1","key":"8615_CR9","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1159\/000356561","volume":"105","author":"OD Saugstad","year":"2014","unstructured":"Saugstad OD, Aune D. Optimal oxygenation of extremely low birth weight infants: a meta-analysis and systematic review of the oxygen saturation target studies. Neonatology. 2014;105(1):55\u201363.","journal-title":"Neonatology"},{"issue":"1","key":"8615_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jpeds.2010.01.046","volume":"157","author":"JM Di Fiore","year":"2010","unstructured":"Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, et al. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010;157(1):69\u201373.","journal-title":"J Pediatr"},{"issue":"8988","key":"8615_CR11","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/S0140-6736(95)92475-2","volume":"346","author":"S Cunningham","year":"1995","unstructured":"Cunningham S, Fleck BW, Elton RA, McIntosh N. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet. 1995;346(8988):1464\u20135.","journal-title":"Lancet"},{"issue":"6","key":"8615_CR12","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/pr.2012.132","volume":"72","author":"JM Di Fiore","year":"2012","unstructured":"Di Fiore JM, Kaffashi F, Loparo K, Sattar A, Schluchter M, Foglyano R, et al. The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants. Pediatr Res. 2012;72(6):606\u201312.","journal-title":"Pediatr Res"},{"issue":"6","key":"8615_CR13","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1001\/jama.2015.8841","volume":"314","author":"CF Poets","year":"2015","unstructured":"Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, et al. Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants. JAMA. 2015;314(6):595\u2013603.","journal-title":"JAMA"},{"issue":"3","key":"8615_CR14","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1159\/000329922","volume":"100","author":"RJ Martin","year":"2011","unstructured":"Martin RJ, Wang K, Koroglu O, Di Fiore J, Kc P. Intermittent hypoxic episodes in preterm infants: do they matter? Neonatology. 2011;100(3):303\u201310.","journal-title":"Neonatology"},{"issue":"4","key":"8615_CR15","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.jpeds.2013.11.072","volume":"164","author":"K Lim","year":"2014","unstructured":"Lim K, Wheeler KI, Gale TJ, Jackson HD, Kihlstrand JF, Sand C, et al. Oxygen saturation targeting in preterm infants receiving continuous positive airway pressure. J Pediatr. 2014;164(4):730-6 e1.","journal-title":"J Pediatr."},{"issue":"1","key":"8615_CR16","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1542\/peds.2010-0939","volume":"127","author":"N Claure","year":"2011","unstructured":"Claure N, Bancalari E, D\u2019Ugard C, Nelin L, Stein M, Ramanathan R, et al. Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants. Pediatrics. 2011;127(1):e76-83.","journal-title":"Pediatrics"},{"issue":"2","key":"8615_CR17","doi-asserted-by":"publisher","first-page":"e379","DOI":"10.1542\/peds.2013-1834","volume":"133","author":"A Hallenberger","year":"2014","unstructured":"Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS, Group CS. Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial. Pediatrics. 2014;133(2):e379\u201385.","journal-title":"Pediatrics"},{"issue":"2","key":"8615_CR18","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1136\/archdischild-2023-325831","volume":"109","author":"TMR Schouten","year":"2024","unstructured":"Schouten TMR, Abu-Hanna A, van Kaam AH, van den Heuvel MEN, Bachman TE, van Leuteren RW, et al. Prolonged use of closed-loop inspired oxygen support in preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2024;109(2):221\u20136.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"4","key":"8615_CR19","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1136\/archdischild-2021-322096","volume":"107","author":"CE Schwarz","year":"2022","unstructured":"Schwarz CE, Kreutzer KB, Langanky L, Wolf NS, Braun W, O\u2019Sullivan MP, et al. Randomised crossover trial comparing algorithms and averaging times for automatic oxygen control in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022;107(4):425\u201330.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"6","key":"8615_CR20","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1136\/archdischild-2020-320728","volume":"106","author":"KP Dijkman","year":"2021","unstructured":"Dijkman KP, Mohns T, Dieleman JP, van Pul C, Goos TG, Reiss IK, et al. Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study. Arch Dis Child Fetal Neonatal Ed. 2021;106(6):621\u20136.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"2","key":"8615_CR21","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1136\/archdischild-2022-324160","volume":"108","author":"V Nair","year":"2023","unstructured":"Nair V, Kannan Loganathan P, Lal MK, Pringleton H, Bachman TE, Brodlie M, et al. Automatic oxygen control for reducing extremes of oxygen saturation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2023;108(2):136\u201341.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"3","key":"8615_CR22","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1111\/apa.15585","volume":"110","author":"S Sturrock","year":"2021","unstructured":"Sturrock S, Ambulkar H, Williams EE, Sweeney S, Bednarczuk NF, Dassios T, et al. A randomised crossover trial of closed loop automated oxygen control in preterm, ventilated infants. Acta Paediatr. 2021;110(3):833\u20137.","journal-title":"Acta Paediatr"},{"issue":"4","key":"8615_CR23","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1136\/archdischild-2019-317029","volume":"105","author":"CE Schwarz","year":"2020","unstructured":"Schwarz CE, Kidszun A, Bieder NS, Franz AR, Konig J, Mildenberger E, et al. Is faster better? A randomised crossover study comparing algorithms for closed-loop automatic oxygen control. Arch Dis Child Fetal Neonatal Ed. 2020;105(4):369\u201374.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"4","key":"8615_CR24","first-page":"F360","volume":"104","author":"M Gajdos","year":"2019","unstructured":"Gajdos M, Waitz M, Mendler MR, Braun W, Hummler H. Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019;104(4):F360\u20135.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"4","key":"8615_CR25","first-page":"F366","volume":"104","author":"PR Reynolds","year":"2019","unstructured":"Reynolds PR, Miller TL, Volakis LI, Holland N, Dungan GC, Roehr CC, et al. Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow. Arch Dis Child Fetal Neonatal Ed. 2019;104(4):F366\u201371.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"5","key":"8615_CR26","doi-asserted-by":"publisher","first-page":"F395","DOI":"10.1136\/archdischild-2016-312172","volume":"102","author":"HA Van Zanten","year":"2017","unstructured":"Van Zanten HA, Kuypers K, Stenson BJ, Bachman TE, Pauws SC, Te Pas AB. The effect of implementing an automated oxygen control on oxygen saturation in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2017;102(5):F395\u20139.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"2","key":"8615_CR27","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/archdischild-2020-318918","volume":"106","author":"HH Salverda","year":"2021","unstructured":"Salverda HH, Cramer SJE, Witlox R, Dargaville PA, Te Pas AB. Automated oxygen control in preterm infants, how does it work and what to expect: a narrative review. Arch Dis Child Fetal Neonatal Ed. 2021;106(2):215\u201321.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"2","key":"8615_CR28","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1097\/MOP.0000000000000993","volume":"33","author":"S Mitra","year":"2021","unstructured":"Mitra S, McMillan D. Automated control of fraction of inspired oxygen: is it time for widespread adoption? Curr Opin Pediatr. 2021;33(2):209\u201316.","journal-title":"Curr Opin Pediatr"},{"issue":"1","key":"8615_CR29","doi-asserted-by":"publisher","first-page":"F5","DOI":"10.1136\/archdischild-2016-311647","volume":"102","author":"CF Poets","year":"2017","unstructured":"Poets CF, Franz AR. Automated FiO2 control: nice to have, or an essential addition to neonatal intensive care? Arch Dis Child Fetal Neonatal Ed. 2017;102(1):F5\u20136.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"3","key":"8615_CR30","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.siny.2015.02.003","volume":"20","author":"N Claure","year":"2015","unstructured":"Claure N, Bancalari E. Closed-loop control of inspired oxygen in premature infants. Semin Fetal Neonatal Med. 2015;20(3):198\u2013204.","journal-title":"Semin Fetal Neonatal Med"},{"key":"8615_CR31","doi-asserted-by":"publisher","first-page":"105462","DOI":"10.1016\/j.earlhumdev.2021.105462","volume":"162","author":"PA Dargaville","year":"2021","unstructured":"Dargaville PA, Marshall AP, McLeod L, Salverda HH, Te Pas AB, Gale TJ. Automation of oxygen titration in preterm infants: current evidence and future challenges. Early Hum Dev. 2021;162:105462.","journal-title":"Early Hum Dev"},{"issue":"4","key":"8615_CR32","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41372-017-0037-z","volume":"38","author":"S Mitra","year":"2018","unstructured":"Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol. 2018;38(4):351\u201360.","journal-title":"J Perinatol"},{"key":"8615_CR33","doi-asserted-by":"publisher","first-page":"c332","DOI":"10.1136\/bmj.c332","volume":"340","author":"Schulz KF, Altman DG, Moher D, Group C","year":"2010","unstructured":"Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.","journal-title":"BMJ"},{"issue":"4","key":"8615_CR34","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/j.1469-8749.1997.tb07414.x","volume":"39","author":"R Palisano","year":"1997","unstructured":"Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39(4):214\u201323.","journal-title":"Dev Med Child Neurol"},{"issue":"7","key":"8615_CR35","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1001\/archopht.123.7.991","volume":"123","author":"International Committee for the Classification of Retinopathy of P","year":"2005","unstructured":"International Committee for the Classification of Retinopathy of P. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123(7):991\u20139.","journal-title":"Arch Ophthalmol"},{"issue":"6","key":"8615_CR36","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/sj.jp.7210963","volume":"23","author":"MC Walsh","year":"2003","unstructured":"Walsh MC, Wilson-Costello D, Zadell A, Newman N, Fanaroff A. Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol. 2003;23(6):451\u20136.","journal-title":"J Perinatol"},{"issue":"1","key":"8615_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00000658-197801000-00001","volume":"187","author":"MJ Bell","year":"1978","unstructured":"Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1\u20137.","journal-title":"Ann Surg."},{"issue":"3","key":"8615_CR38","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1001\/jamaophthalmol.2018.5984","volume":"137","author":"LEH Smith","year":"2019","unstructured":"Smith LEH, Hellstr\u00f6m A, Stahl A, Fielder A, Chambers W, Moseley J, et al. Development of a retinopathy of prematurity activity scale and clinical outcome measures for use in clinical trials. Jama Ophthalmol. 2019;137(3):305\u201311.","journal-title":"Jama Ophthalmol"},{"key":"8615_CR39","first-page":"351","volume":"37","author":"PH van Elteren","year":"1960","unstructured":"van Elteren PH. On the combination of independent two-sample tests of Wilcoxon. Bulletin of the International Statistical Institute. 1960;37:351\u201361.","journal-title":"Bulletin of the International Statistical Institute"},{"issue":"5","key":"8615_CR40","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.cct.2010.07.005","volume":"31","author":"R Bender","year":"2010","unstructured":"Bender R, Vervolgyi V. Estimating adjusted NNTs in randomised controlled trials with binary outcomes: a simulation study. Contemp Clin Trials. 2010;31(5):498\u2013505.","journal-title":"Contemp Clin Trials"},{"key":"8615_CR41","volume-title":"Discrete multivariate analysis: theory and practice","author":"YMM Bishop","year":"1975","unstructured":"Bishop YMM, Fienberg SE, Holland PW. Discrete multivariate analysis: theory and practice. Cambridge, Mass: MIT Press; 1975."},{"issue":"2","key":"8615_CR42","doi-asserted-by":"publisher","first-page":"224","DOI":"10.7326\/0003-4819-107-2-224","volume":"107","author":"KA L'Abbe","year":"1987","unstructured":"L\u2019Abbe KA, Detsky AS, O\u2019Rourke K. Meta-analysis in clinical research. Ann Intern Med. 1987;107(2):224\u201333.","journal-title":"Ann Intern Med"},{"issue":"2","key":"8615_CR43","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1136\/archdischild-2020-319058","volume":"106","author":"CE Schwarz","year":"2021","unstructured":"Schwarz CE, Lightbody G, Muller-Hansen I, Arand J, Poets CF, Franz AR. In vitro evaluation of delays in the adjustment of the fraction of inspired oxygen during CPAP: effect of flow and volume. Arch Dis Child Fetal Neonatal Ed. 2021;106(2):205\u20137.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"4","key":"8615_CR44","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1136\/archdischild-2023-325961","volume":"109","author":"CA Maiwald","year":"2024","unstructured":"Maiwald CA, Schwarz CE, Bockmann K, Springer L, Poets CF, Franz A. Randomised crossover study on pulse oximeter readings from different sensors in very preterm infants. Arch Dis Child Fetal Neonatal Ed. 2024;109(4):391\u20136.","journal-title":"Arch Dis Child Fetal Neonatal Ed"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08615-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-024-08615-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08615-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T17:04:23Z","timestamp":1731431063000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-024-08615-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["8615"],"URL":"https:\/\/doi.org\/10.1186\/s13063-024-08615-7","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]},"assertion":[{"value":"13 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The FiO<sub>2<\/sub>-C trial was performed in accordance with the Declaration of Helsinki and the guidelines of Good Clinical Practice. Parents or guardians of the participating infants were informed about the trial and their written informed consent was required before inclusion.The study was approved by all ethics committees of the participating institutions; it was also approved by the German authority BfArM (Bundesinstitut f\u00fcr Arzneimittel und Medizinprodukte) as it was conducted as pharmaceutical trial in Germany with the investigational medicinal product \u2018oxygen\u2019. The study was also a medicinal product study within the intended use of studied devices.<i>Ethics:<\/i>\u2022 Ethics Committee of Northwest Woman and Children Hospital, Xi\u2019an, China; Document No. 21-041\u201418th Oct 2021\u2022 Ethics Committee at the University Hospital T\u00fcbingen, reference no. 170\/2018AMG1, approved; Adviescommissie Onderzoek M\u00e1xima Medisch Centrum, Veldhoven, the Netherlands METC-No. w18.061, CCMO-No.: N165766.015.l8\u20141 April 2019\u2022 West of Scotland Research Ethics Service, Paisley, UK; IRAS Project ID: 317261, REC-reference 22\/WS\/0143\u201422 November 2022, Health Research Authority approval IRAS Project ID: 317261\u201425 November 2022<i>Authority:<\/i>\u2022 BfArM, reference no. 4042695 approved conduct","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors and collaborators gave consent for publication. No personal data of participants is presented here.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All contributors declare that they do not have competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"756"}}