荷兰阿玛利亚儿童医院Willem P. de Boode团队近期取得重要工作进展，他们研究比较了动脉导管未闭（PDA）的预期管理治疗和早期布洛芬治疗方法。相关研究成果2022年12月6日在线发表于《新英格兰医学杂志》上。

据介绍，环氧合酶抑制剂通常用于患有动脉导管未闭的婴儿，但这些药物的疗效尚不确定。

在这项多中心、非劣效性试验中，研究人员将经超声心动图确认的PDA（直径>1.5mm，左向右分流）极早产（孕龄<28周）婴儿随机分为两组，一组接受预期治疗，另一组接受早期布洛芬治疗。综合主要结局包括坏死性小肠结肠炎（贝尔氏IIa期或更高）、中度至重度支气管肺发育不良或月经后36周死亡。与早期布洛芬治疗相比，预期治疗的非劣效性定义为单侧95%置信区间上限小于10个百分点的绝对风险差异。

共有273名婴儿接受了随机分组，胎龄中位数为26周，出生体重中位数为845g。预期管理组136名婴儿中有63名（46.3%）发生主要结局事件，早期布洛芬组137名婴儿中87名（63.5%）发生主要结果局事件（绝对风险差异，−17.2个百分点；单侧95%置信区间[CI]的上边界，−7.4; 非劣效性P<0.001）。预期管理组136名婴儿中有24名（17.6%）发生坏死性小肠结肠炎，早期布洛芬组137名中有21名（15.3%）（绝对风险差异，2.3个百分点；双侧95%可信区间，−6.5至11.1）；117名婴儿中39名（33.3%）和112名婴儿中57名（50.9%）分别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%可信区间，−30.2至−5.0)； 预期管理组中136名婴儿中有19名（14.0%）死亡，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%可信区间，−13.0至4.4）。两组的其他不良结果发生率相似。

研究结果表明，就坏死性小肠结肠炎、支气管肺发育不良或月经后36周死亡而言，极早产儿PDA的预期治疗不亚于早期布洛芬治疗。

附：英文原文

Title: Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus | NEJM

Author: Tim Hundscheid, M.D.,, Wes Onland, M.D., Ph.D.,, Elisabeth M.W. Kooi, M.D., Ph.D.,, Daniel C. Vijlbrief, M.D., Ph.D.,, Willem B. de Vries, M.D., Ph.D.,, Koen P. Dijkman, M.D.,, Anton H. van Kaam, M.D., Ph.D.,, Eduardo Villamor, M.D., Ph.D.,, André A. Kroon, M.D., Ph.D.,, Remco Visser, M.D., Ph.D.,, Susanne M. Mulder-de Tollenaer, M.D.,, Barbara De Bisschop, M.D.,, Peter H. Dijk, M.D., Ph.D.,, Daniela Avino, M.D.,, Catheline Hocq, M.D.,, Alexandra Zecic, M.D.,, Marisse Meeus, M.D.,, Tessa de Baat, M.D.,, Frank Derriks, M.D.,, Tine B. Henriksen, M.D., Ph.D.,, Kasper J. Kyng, M.D., Ph.D.,, Rogier Donders, Ph.D.,, Debbie H.G.M. Nuytemans,, Bart Van Overmeire, M.D., Ph.D.,, Antonius L. Mulder, M.D., Ph.D.,, and Willem P. de Boode, M.D., Ph.D.

Issue&Volume: 2022-12-06

Abstract: 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.

DOI: 10.1056/NEJMoa2207418

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2207418