• Tim Hundscheid, Wes Onland, KooiElisabeth M WEMWFrom the Department of Pediatrics, Division of Neonatology (T.H., W.P.B.), and the Department for Health Evidence (R.D.), Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, t, Daniel C Vijlbrief, Willem B de Vries, Koen P Dijkman, Anton H van Kaam, Eduardo Villamor, André A Kroon, Remco Visser, Susanne M Mulder-de Tollenaer, Barbara De Bisschop, Peter H Dijk, Daniela Avino, Catheline Hocq, Alexandra Zecic, Marisse Meeus, Tessa de Baat, Frank Derriks, Tine B Henriksen, Kasper J Kyng, Rogier Donders, Debbie H G M Nuytemans, Bart Van Overmeire, Antonius L Mulder, Willem P de Boode, and BeNeDuctus Trial Investigators.
• From the Department of Pediatrics, Division of Neonatology (T.H., W.P.B.), and the Department for Health Evidence (R.D.), Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, the Department of Neonatology, Amsterdam Reproduction and Development, Emma Children's Hospital, Amsterdam University Medical Centers (W.O., W.B.V., A.H.K., T.B.), and Neonatology Network Netherlands (D.H.G.M.N.), Amsterdam, University Medical Center Groningen, Beatrix Children's Hospital, and the Department of Pediatrics, Division of Neonatology, University of Groningen (E.M.W.K., P.H.D.), Groningen, the Division of Woman and Baby, Department of Neonatology, University Medical Center Utrecht, Utrecht University, Wilhelmina Children's Hospital, Utrecht (D.C.V., W.B.V.), the Department of Neonatology, Maxima Medical Center Veldhoven, Veldhoven (K.P.D.), Maastricht University Medical Center, the Department of Pediatrics, Division of Neonatology, School for Oncology and Reproduction, University of Maastricht, Maastricht (E.V.), the Department of Pediatrics, Division of Neonatology, Erasmus Medical Center Rotterdam, Sophia Children's Hospital, Rotterdam (A.A.K.), the Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Willem Alexander Children's Hospital, Leiden (R.V.), and the Department of Pediatrics, Division of Neonatology, Isala Women's and Children's Hospital Zwolle, Zwolle (S.M.M.-T.) - all in the Netherlands; the Department of Neonatology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel (B.D.B.), the Department of Pediatrics, Division of Neonatology, Hôpital Universitaire des Enfants Reine Fabiola (D.A.), the Department of Pediatrics, Division of Neonatology, Cliniques Universitaires St. Luc (C.H.), the Department of Neonatology, Cliniques Universitaires de Bruxelles, Hôpital Erasme (F.D., B.V.O.), and Kind en Gezin-Opgroeien, Flemish Government, Sint-Gillis (B.V.O.), Brussels, the Department of Pediatrics, Division of Neonatology, Ghent University Hospital, Ghent (A.Z.), and the Department of Neonatology, Antwerp University Hospital, Edegem (A.L.M., M.M.) - all in Belgium; and the Departments of Pediatrics and Adolescent Medicine and Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark (T.B.H., K.J.K.).
• N. Engl. J. Med. 2023 Mar 16; 388 (11): 980990980-990.

BackgroundCyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.MethodsIn this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points.ResultsA total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], -7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups.ConclusionsExpectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.).Copyright © 2022 Massachusetts Medical Society.

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