胎龄 ≤ 29周早产儿血流动力学意义动脉导管 未闭的危险因素及临床结局分析

Analysis of Risk Factors and Clinical Outcomes of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants Born at ≤29 Weeks of Gestation

摘要: 目的：回顾性分析胎龄 ≤ 29周早产儿血流动力学意义动脉导管未闭(hemodynamically significant patent ductus arteriosus, hsPDA)的临床特征，探讨其危险因素及对临床结局的影响。方法：选取2018年3月至2023年9月于青岛大学附属医院出生并入住新生儿重症监护病房、胎龄 ≤ 29周的早产儿为研究对象。根据生后2周是否合并hsPDA分为hsPDA组与非hsPDA组。收集新生儿一般情况、孕母情况、住院期间临床资料及PDA药物治疗情况。采用倾向性评分匹配法平衡胎龄、出生体重及性别等基线混杂因素，并在匹配样本中重新构建以hsPDA为因变量的多因素Logistic回归模型。结果：共纳入108例早产儿，hsPDA发生率为37.0%。hsPDA组胎龄显著小于非hsPDA组(27.30周vs 28.15周，P < 0.001)，需肺表面活性物质治疗的呼吸窘迫综合征比例(77.5% vs 36.8%, P < 0.001)及早发败血症比例(25.0% vs 7.4%, P = 0.010)显著更高。倾向性评分匹配后，hsPDA组支气管肺发育不良相关肺动脉高压发生率(52.6% vs 21.1%, P = 0.004)、机械通气比例(57.9% vs 34.2%, P = 0.038)及机械通气时间、氧疗时间、住院时间均显著更高或更长。多因素分析显示，胎龄(OR = 0.427, 95%CI: 0.253~0.722)、需肺表面活性物质治疗的呼吸窘迫综合征(OR = 6.872, 95%CI: 2.527~18.687)及早发败血症(OR = 4.037, 95%CI: 1.072~15.201)是hsPDA的独立影响因素；匹配后，需肺表面活性物质治疗的呼吸窘迫综合征仍与hsPDA发生风险升高相关(OR = 6.211, 95%CI: 2.222~17.241)。结论：胎龄较小及需肺表面活性物质治疗的呼吸窘迫综合征是胎龄 ≤ 29周早产儿发生hsPDA的重要危险因素。hsPDA与支气管肺发育不良相关肺动脉高压、机械通气需求增加以及机械通气、氧疗和住院时间延长相关；但布洛芬治疗可能影响结局解释，相关关联仍需在更大样本中通过治疗分层或敏感性分析进一步验证。

Abstract: Objective: To retrospectively analyze the clinical characteristics of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants born at ≤29 weeks of gestation and to evaluate its risk factors and impact on clinical outcomes. Methods: Preterm infants born at ≤29 weeks of gestation and admitted to the Neonatal Intensive Care Unit of The Affiliated Hospital of Qingdao University between March 2018 and September 2023 were included. Infants were divided into hsPDA and non-hsPDA groups according to the presence of hsPDA at 2 weeks after birth. Neonatal characteristics, maternal factors, in-hospital clinical data, and PDA-related pharmacological treatment were collected. Propensity score matching was used to balance baseline confounders, including gestational age, birth weight, and sex. A multivariable Logistic regression model with hsPDA as the dependent variable was re-established in the matched cohort. Results: A total of 108 preterm infants were included, and the incidence of hsPDA was 37.0%. The hsPDA group had a lower gestational age than the non-hsPDA group (27.30 weeks vs 28.15 weeks, P < 0.001), and higher proportions of respiratory distress syndrome requiring pulmonary surfactant treatment (77.5% vs 36.8%, P < 0.001) and early-onset sepsis (25.0% vs 7.4%, P = 0.010). After propensity score matching, the hsPDA group had higher rates of bronchopulmonary dysplasia-associated pulmonary hypertension (52.6% vs 21.1%, P = 0.004) and mechanical ventilation (57.9% vs 34.2%, P = 0.038), as well as longer durations of mechanical ventilation, oxygen therapy, and hospitalization. Multivariable analysis showed that gestational age (OR = 0.427, 95%CI: 0.253~0.722), respiratory distress syndrome requiring pulmonary surfactant treatment (OR = 6.872, 95%CI: 2.527~18.687), and early-onset sepsis (OR = 4.037, 95%CI: 1.072~15.201) were independently associated with hsPDA. In the matched cohort, respiratory distress syndrome requiring pulmonary surfactant treatment remained associated with increased odds of hsPDA (OR = 6.211, 95%CI: 2.222~17.241). Conclusion: Lower gestational age and respiratory distress syndrome requiring pulmonary surfactant treatment are important risk factors for hsPDA in preterm infants born at ≤29 weeks of gestation. hsPDA is associated with increased risks of bronchopulmonary dysplasia-associated pulmonary hypertension and mechanical ventilation, as well as prolonged mechanical ventilation, oxygen therapy, and hospitalization. The potential influence of ibuprofen treatment should be considered when interpreting outcome associations and should be further examined using treatment-stratified or sensitivity analyses in larger cohorts.