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动脉导管未闭分流大小和持续时间对中国早产儿死亡或严重呼吸系统并发症风险的影响。

Impact of patent ductus arteriosus shunt size and duration on risk of death or severe respiratory morbidity in preterm infants born in China.

机构信息

Division of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Street, Minhang District, Shanghai, 201102, China.

Department of Neonatology, Kunshan Maternity and Children's Health Care Hospital, 5 Qingyang Middle Road, Kunshan, Jiangsu, 215300, China.

出版信息

Eur J Pediatr. 2022 Aug;181(8):3131-3140. doi: 10.1007/s00431-022-04549-x. Epub 2022 Jul 15.

Abstract

The purpose of this study is to assess whether duration and size of the arterial duct were associated with severe respiratory morbidity and mortality in preterm infants. All echocardiography evaluations for patent ductus arteriosus (PDA) in a cohort of preterm infants, born at a gestational age less than 28 weeks, from birth up to 36 weeks of postconceptional age or final ductal closure were reviewed. Ductal size was measured at the pulmonary end. PDA was classified as small (E1: ductal diameter (DD) ≤ 1.5 mm), moderate (E2: 1.5 mm < DD ≤ 2.5 mm), or large (E3) (DD > 2.5 mm). The primary outcome was adverse outcome defined by the composite outcome of bronchopulmonary dysplasia (BPD) or death. Infants in whom the primary outcome occurred were classified as "high-risk" whereas patients who did not satisfy this outcome were classified as "low-risk". Intergroup comparison (high vs. low risk) was performed using univariate and multivariate analyses. A total of 135 infants, born between 2010 and 2020, were evaluated. The primary outcome was satisfied in 46 (34.1%) patients. The high-risk group was characterized by increased duration of exposure to PDA of any (E1/E2/E3) grade (44 vs. 25.5 days, p = .0004), moderate or large (E2/E3) PDA (30.5 vs. 11.5 days, p < .0001), moderate (E2) PDA (10.8 vs.6 days, p = 0.05), and large (E3) PDA (11.5 vs.0 days, p < .0001) compared with low-risk group. Lower gestational age, prolonged duration of mechanical ventilation, higher rate of inotrope use, pharmacological therapy, and PDA ligation were also associated with development of BPD or death (high-risk group). After adjusting for confounders, the rate of inotrope use [OR 2.688, 95% CI (1.011-7.142), p = 0.047], duration of large (E3) PDA [OR 1.060, 95% CI (1.005-1.118), p = 0.03], and mechanical ventilation [OR 1.130, 95% CI (1.064-1.200), p = 0.0001] were independently associated with the composite of BPD or death. Among infants who developed BPD, 27 were classified as grade I and 18 as grade II BPD, respectively. Infants with grade II BPD had prolonged MV (20.0 vs. 9.0 days, p = 0.024), prolonged exposure to PDA of any grade (55.8 vs. 36.0 days, p = 0.03), and prolonged exposure to large (E3) PDA compared with infants with grade I BPD.   Conclusion: Prolonged exposure to a large PDA was associated with severe respiratory morbidity and mortality in preterm infants. The modulator role of early intervention, in the most pathologic shunts, on severe respiratory morbidity in preterm infants should be tested in well-designed clinical trials. What is Known: • Current guidelines recommended against accelerating PDA closure of preterm infants within 2 weeks of life, with low certainty evidence indicating improved long-term outcomes. • Recent studies suggest that conservative approach regarding PDA management has detrimental effects on the respiratory outcomes in a subgroup population. What is New: • Persistent patency of significant PDA is associated with increased risk of BPD/death in extremely preterm infants. • Targeted intervention of PDA is beneficial for the at-risk preterm infants with increased PDA hemodynamic significance.

摘要

本研究旨在评估动脉导管(PDA)的持续时间和大小与早产儿严重呼吸系统发病率和死亡率的关系。

对出生胎龄小于 28 周的早产儿队列进行了所有 PDA 的超声心动图评估,从出生到孕后 36 周或最终导管关闭。在肺动脉端测量导管的大小。PDA 分为小(E1:导管直径(DD)≤1.5mm)、中(E2:1.5mm<DD≤2.5mm)和大(E3)(DD>2.5mm)。主要结局是由支气管肺发育不良(BPD)或死亡组成的复合结局不良。发生主要结局的婴儿被归类为“高危”,而未满足此结局的患者被归类为“低危”。使用单变量和多变量分析进行组间比较(高 vs. 低风险)。共评估了 135 名 2010 年至 2020 年出生的婴儿。主要结局在 46 名(34.1%)患者中得到满足。高危组的特点是 PDA 持续时间更长(任何等级的 E1/E2/E3)(44 天 vs. 25.5 天,p=0.0004)、中或大(E2/E3)PDA(30.5 天 vs. 11.5 天,p<0.0001)、中(E2)PDA(10.8 天 vs. 6 天,p=0.05)和大(E3)PDA(11.5 天 vs. 0 天,p<0.0001)与低危组相比。较低的胎龄、较长的机械通气时间、较高的儿茶酚胺使用率、药物治疗和 PDA 结扎也与 BPD 或死亡的发生相关(高危组)。调整混杂因素后,儿茶酚胺使用率[比值比(OR)2.688,95%可信区间(CI)(1.011-7.142),p=0.047]、大(E3)PDA 持续时间[OR 1.060,95%CI(1.005-1.118),p=0.03]和机械通气[OR 1.130,95%CI(1.064-1.200),p=0.0001]与 BPD 或死亡的复合结局独立相关。在发生 BPD 的婴儿中,27 例被归类为 I 级,18 例被归类为 II 级 BPD。II 级 BPD 婴儿的 MV 时间更长(20.0 天 vs. 9.0 天,p=0.024)、任何等级的 PDA 暴露时间更长(55.8 天 vs. 36.0 天,p=0.03)和大(E3)PDA 暴露时间更长,与 I 级 BPD 婴儿相比。结论:早产儿持续暴露于大 PDA 与严重呼吸系统发病率和死亡率相关。应在精心设计的临床试验中测试早期干预对早产儿严重呼吸系统发病率的调节作用,这种干预作用在最病态的分流中更为明显。

已知内容

  • 当前指南建议早产儿在出生后 2 周内避免加速 PDA 关闭,低确定性证据表明改善了长期结局。

  • 最近的研究表明,对于 PDA 管理的保守方法对亚组人群的呼吸结局有不利影响。

未知内容

  • 持续性显著 PDA 与极早产儿 BPD/死亡风险增加相关。

  • 对具有增加的 PDA 血流动力学意义的高危早产儿进行 PDA 靶向干预是有益的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a5/9352633/02e4e49e4855/431_2022_4549_Fig1_HTML.jpg

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