Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus

被引：123

作者：

Hundscheid, Tim ^{[1
,20
,21
,22
]}

Onland, Wes ^{[3
]}

Kooi, Elisabeth M. W. ^{[5
,6
]}

Vijlbrief, Daniel C. ^{[7
]}

de Vries, Willem B. ^{[3
,7
]}

Dijkman, Koen P. ^{[8
]}

van Kaam, Anton H. ^{[3
]}

Villamor, Eduardo ^{[9
]}

Kroon, Andre A. ^{[10
]}

Visser, Remco ^{[11
]}

Mulder-de Tollenaer, Susanne M. ^{[12
]}

De Bisschop, Barbara ^{[13
]}

Dijk, Peter H. ^{[5
]}

Avino, Daniela ^{[14
]}

Hocq, Catheline ^{[15
]}

Zecic, Alexandra ^{[18
]}

Meeus, Marisse ^{[19
]}

de Baat, Tessa ^{[3
]}

Derriks, Frank ^{[16
]}

Henriksen, Tine B.

Kyng, Kasper J. ^{[20
,21
,22
]}

Donders, Rogier ^{[2
]}

Nuytemans, Debbie H. G. M. ^{[4
,6
]}

Van Overmeire, Bart ^{[16
,17
]}

Mulder, Antonius L. ^{[19
]}

de Boode, Willem P. ^{[1
,23
]}

机构：

[1] Radboud Univ Nijmegen, Amalia Childrens Hosp, Radboud Inst Hlth Sci, Dept Pediat,Div Neonatol,Med Ctr, Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Amalia Childrens Hosp, Radboud Inst Hlth Sci, Dept Hlth Evidence, Nijmegen, Netherlands

[3] Univ Amsterdam, Emma Childrens Hosp, Dept Neonatol, Amsterdam Reprod & Dev,Med Ctr, Amsterdam, Netherlands

[4] Neonatol Network Netherlands, Amsterdam, Netherlands

[5] Univ Med Ctr Groningen, Beatrix Childrens Hosp, Groningen, Netherlands

[6] Univ Groningen, Dept Pediat, Div Neonatol, Groningen, Netherlands

[7] Univ Utrecht, Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Neonatol, Utrecht, Netherlands

[8] Maxima Med Ctr Veldhoven, Dept Neonatol, Veldhoven, Netherlands

[9] Univ Maastricht, Maastricht Univ, Sch Oncol & Reprod, Dept Pediat,Med Ctr,Div Neonatol, Maastricht, Netherlands

[10] Sophia Childrens Univ Hosp, Erasmus Med Ctr Rotterdam, Dept Pediat, Div Neonatol, Rotterdam, Netherlands

[11] Leiden Univ, Willem Alexander Childrens Hosp, Dept Pediat, Div Neonatol,Med Ctr, Leiden, Netherlands

[12] Isala Womens & Childrens Hosp Zwolle, Dept Pediat, Div Neonatol, Zwolle, Netherlands

[13] Univ Ziekenhuis Brussel, Vrije Univ Brussel, Dept Neonatol, Jette, Belgium

[14] Hop Univ Enfants Reine Fabiola, Dept Pediat, Div Neonatol, Brussels, Belgium

[15] Clin Univ St Luc, Dept Pediat, Div Neonatol, Brussels, Belgium

[16] Hop Erasme, Clin Univ Bruxelles, Dept Neonatol, Anderlecht, Belgium

[17] Flemish Govt, Kind Gezin Opgroeien, Brussels, Belgium

[18] Ghent Univ Hosp, Dept Pediat, Div Neonatol, Ghent, Belgium

[19] Antwerp Univ Hosp, Dept Neonatol, Edegem, Belgium

[20] Aarhus Univ, Dept Pediat, Aarhus, Denmark

[21] Aarhus Univ Hosp, Dept Adolescent Med & Clin Med, Aarhus, Denmark

[22] Aarhus Univ, Aarhus, Denmark

[23] Radboud Univ Nijmegen, Amalia Childrens Hosp, Radboud Inst Hlth Sci, Dept Neonatol,Med Ctr, Geert Grooteplein Zuid 10, NL-6525 GA Nijmegen, Netherlands

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2023年 / 388卷 / 11期

关键词：

BIRTH-WEIGHT INFANTS; PRETERM INFANTS; BRONCHOPULMONARY DYSPLASIA; NECROTIZING ENTEROCOLITIS; SEVERITY SCORE; CLOSURE; INDOMETHACIN; ASSOCIATION; SURVIVAL; RISK;

D O I：

10.1056/NEJMoa2207418

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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, ; EudraCT number, .)

引用

页码：980 / 990

页数：11

共 35 条

[1] Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell [J].