布洛芬治疗动脉导管未闭的疗效及并发症研究

目的：探讨症状性动脉导管未闭（sPDA）与非症状性动脉导管未闭（nsPDA）经药物干预后关闭率及相关并发症的发生率，以便进一步指导临床应用。方法：回顾性分析同济医院新生儿科2016 年5 月至2019 年4 月收治的胎龄<34 周并于生后1 周末行超声心动图诊断为动脉导管未闭（PDA）的早产儿252 例，根据是否符合sPDA 诊断标准，分为sPDA 组（n=94例）和nsPDA 组（n=158例），nsPDA 组分为nsPDA-1组（n=92）和nsPDA-2组（n=66）。sPDA 组所有患儿和nsPDA-1组在住院期间均接受了口服布洛芬治疗；而nsPDA-2组患儿在住院期间未接受布洛芬治疗。三组患儿于治疗结束后或出院前均已复查超声心动图。收集患儿资料，分析三组早产儿动脉导管关闭率和PDA 相关并发症的发生情况。结果：sPDA 组患儿胎龄、出生体质量均小于nsPDA-1组和nsPDA-2组（P<0.05），而nsPDA-1组和nsPDA-2组胎龄和出生体质量差异均无统计学意义（P>0.05）。口服布洛芬治疗后sPDA组与nsPDA-1组分别有52例和81例患儿动脉导管关闭，关闭率为55.3%和88.0%，而nsPDA-2组有54例早产儿动脉导管自然关闭，关闭率为81.8%，sPDA 组动脉导管关闭率低于nsPDA-1组和nsPDA-2组（P<0.05），而nsPDA-1组和nsPDA-2组关闭率差异无统计学意义（P>0.05）。sPDA组肺炎、早产儿支气管肺发育不良（BPD）、喂养不耐受、坏死性小肠结肠炎（NEC）及颅内出血（IVH）的发生率高于nsPDA-1组和nsPDA-2组（P<0.05），而nsPDA-1组和nsPDA-2组上述并发症发生率差异无统计学意义（P>0.05）。sPDA 组和nsPDA-1组的肾损伤发生率差异无统计学意义（P>0.05），但均高于nsPDA-2（P<0.05）。结论：胎龄越小、出生体质量越低，出现sPDA可能性越大，sPDA早产儿1周后口服布洛芬关闭PDA 的疗效较nsPDA早产儿差，并较后者更容易出现早产儿相关并发症（肺炎、BPD、喂养不耐受、NEC及IVH）。

Efficacy and Complications of Ibuprofen in the Treatment of Patent Ductus Arteriosus

Objective: To probe into the closure rate of symptomatic patent ductus arteriosus (sPDA) and non-symptomatic patent ductus arteriosus (nsPDA) after drug intervention and analyze the incidence of related complications, so as to further guide the clinical application. Methods: Retrospective analysis was performed on 252 cases of preterm infants with gestational age <34 weeks and diagnosed as patent ductus arteriosus (PDA) by echocardiography at the first weekend after birth from the neonatology department of Tongji Hospital from May 2016 to Apr. 2019. According to the sPDA diagnostic criteria, all patients were divided into 94 cases in the sPDA group and 158 cases in the nsPDA group. The nsPDA group was divided into 92 cases in the nsPDA-1 group and 66 cases in the nsPDA-2 group. All children in the sPDA group and the nsPDA-1 group received oral ibuprofen during the hospitalization. Children in the nsPDA-2 group were not treated with ibuprofen during the hospitalization. Echocardiography was reviewed on all preterm infants after treatment or before discharge. Clinical data of three groups were collected to analyze the closure rate of PDA and the incidence of related complications related to PDA. Results: The gestational age and birth weight of children in the sPDA group were lower than those in the nsPDA-1 group and the nsPDA-2 group (P<0.05), yet there was no significant difference in gestational age and birth weight between the nsPDA-1 group and the nsPDA-2 group (P>0.05). After oral ibuprofen treatment, ductus arteriosus was closed in 52 cases in the sPDA group and 81 cases in the nsPDA-1 group, and the closure rate was 55.3% and 88.0%. In the nsPDA-2 group, 54 cases of preterm infants had natural ductus arteriosus closure, with the closure rate of 81.8%. The ductus arteriosus closure rate in the sPDA group was lower than that in the nsPDA-1 group and the nsPDA-2 group (P<0.05), yet there was no significant difference in the closure rate of ductus arteriosus between the nsPDA-1 group and the nsPDA-2 group (P>0.05). The incidence of pneumonia, bronchopulmonary dysplasia (BPD), feeding intolerance, necrotizing enterocolitis (NEC) and intracranial hemorrhage (IVH) in the sPDA group was higher than that in the nsPDA-1 group and the nsPDA-2 group (P<0.05), yet there was no statistically significant difference in the incidence of above complications between the nsPDA-1 group and the nsPDA-2 group (P>0.05). There was no significant difference in the incidence of renal injury between the sPDA group and the nsPDA-1 group (P>0.05), but both were higher than those in the nsPDA-2 group (P<0.05). Conclusion: The incidence of sPDA is higher in preterm infants with younger gestational age and lower birth weight. Premature infants with sPDA have poor efficacy in oral ibuprofen treatment, and are more likely to have related complications (pneumonia, BPD, feeding intolerance, NEC and IVH).