期待治疗或早期布洛芬治疗动脉导管未闭。
Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.
机构信息
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.).
出版信息
N Engl J Med. 2023 Mar 16;388(11):980-990. doi: 10.1056/NEJMoa2207418. Epub 2022 Dec 6.
BACKGROUND
Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.
METHODS
In 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.
RESULTS
A 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.
CONCLUSIONS
Expectant 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.).
背景
环氧化酶抑制剂常用于患有动脉导管未闭（PDA）的婴儿，但这些药物的益处尚不确定。
方法
在这项多中心非劣效性试验中，我们随机分配了经超声心动图证实患有 PDA（直径>1.5 毫米，存在左向右分流）的极早产儿（<28 周胎龄），分别接受期待治疗或早期布洛芬治疗。复合主要结局包括坏死性小肠结肠炎（Bell Ⅱa 期或更高）、中重度支气管肺发育不良或 36 周校正胎龄死亡。期待治疗与早期布洛芬治疗的非劣效性定义为单侧 95%置信区间上限的绝对风险差异小于 10 个百分点。
结果
共有 273 名婴儿接受了随机分组。中位胎龄为 26 周，中位出生体重为 845 克。期待治疗组 136 名婴儿中有 63 名（46.3%）和早期布洛芬组 137 名婴儿中有 87 名（63.5%）发生主要结局事件（绝对风险差异，-17.2 个百分点；单侧 95%置信区间上限[-7.4]；P<0.001 为非劣效性）。期待治疗组 136 名婴儿中有 24 名（17.6%）和早期布洛芬组 137 名婴儿中有 21 名（15.3%）发生坏死性小肠结肠炎（绝对风险差异，2.3 个百分点；双侧 95%置信区间[-6.5，11.1]）；期待治疗组 117 名婴儿中有 39 名（33.3%）和早期布洛芬组 112 名婴儿中有 57 名（50.9%）发生支气管肺发育不良（绝对风险差异，-17.6 个百分点；双侧 95%置信区间[-30.2，-5.0]）。期待治疗组 136 名婴儿中有 19 名（14.0%）和早期布洛芬组 137 名婴儿中有 25 名（18.2%）死亡（绝对风险差异，-4.3 个百分点；双侧 95%置信区间[-13.0，4.4]）。两组其他不良结局的发生率相似。
结论
对于极早产儿的 PDA，期待治疗与早期布洛芬治疗在坏死性小肠结肠炎、支气管肺发育不良或 36 周校正胎龄死亡方面无差异。（由荷兰健康研究与发展组织和比利时医疗保健知识中心资助；BeNeDuctus 临床试验。gov 编号，NCT02884219；EudraCT 编号，2017-001376-28。）
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