探讨口服布洛芬与对乙酰氨基酚治疗有血流动力学意义动脉导管未闭(hsPDA)超早产儿(出生胎龄<28周)的疗效及安全性。

选择2012年11月至2019年10月，上海市第一妇婴保健院收治的符合本研究纳入与排除标准的96例hsPDA超早产儿为研究对象。根据采取的口服药物治疗方案，将其分为布洛芬组(n＝53)与对乙酰氨基酚组(n＝43)。2组患儿达到全肠道喂养时间、有创机械通气时间及口服药物治疗前、后动脉导管内径比较，采用成组t检验。2组患儿接受口服药物治疗后，动脉导管关闭率、并发症发生率、口服药物治疗失败后中转手术治疗率及患儿病死率比较，采用χ²检验或Fisher确切概率法。2组患儿性别构成比、出生胎龄、出生体重，生后1、5 min Apgar评分，肺表面活性物质使用率、接受口服药物治疗时日龄，以及母亲产前地塞米松促胎肺成熟治疗率、剖宫产术分娩率、胎膜早破持续时间>18 h所占比例等一般临床资料比较，差异均无统计学意义(P>0.05)。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。

①布洛芬组患儿动脉导管关闭率为56.6%(30/53)，显著高于对乙酰氨基酚组的30.2%(13/43)，并且差异有统计学意义(χ²＝6.676、P＝0.009)。接受口服药物治疗后，布洛芬组患儿动脉导管内径为(0.14±0.26) cm，显著小于对乙酰氨基酚组的(0.30±0.14) cm，并且差异有统计学意义(t＝-5.406、P＝0.007)。②2组患儿达到全肠道喂养时间及有创机械通气时间分别比较，差异均无统计学意义(P>0.05)。③2组患儿肝、肾功能损害及高胆红素血症、血小板减少、贫血、胃肠道出血、肺出血、脑室内出血(IVH)、早发型败血症(EOS)、晚发型败血症(LOS)、支气管肺发育不良(BPD)、坏死性小肠结肠炎(NEC)、早产儿视网膜病变(ROP)发生率，以及口服药物治疗失败后中转手术治疗率、患儿病死率分别比较，差异均无统计学意义(P>0.05)。

布洛芬治疗hsPDA超早产儿的安全性与对乙酰氨基酚相似，但是其治疗疗效，显著高于对乙酰氨基酚。由于本研究仅为单中心研究，纳入样本量相对较小，因此布洛芬与对乙酰氨基酚治疗hsPDA超早产儿的疗效及安全性比较，尚需大样本、多中心、随机对照试验进一步研究、证实。

To explore and compare the efficacy and safety of oral ibuprofen and paracetamol in treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in extreme premature neonates (gestational age < 28 weeks).

A total of 96 extreme premature neonates with hsPDA who met the inclusion and exclusion criteria of this study from November 2012 to October 2019 in Shanghai First Maternity and Infant Hospital were selected as research subjects. They were classified into two groups according to oral medication regimen for treatment of hsPDA in extreme premature neonates: ibuprofen group (n=53) and paracetamol group (n=43). The time to full enteral feeding, duration of invasive mechanical ventilation and inner diameter of ductus arteriosus before and after medication between two groups were compared by independent-samples t tests. The rate of closure of ductus arteriosus, incidence of complications, rate of failure of oral medication and transfer to surgery and mortality of neonates after medication between two groups were compared by chi-square test or Fisher′s exact test. There were no statistical differences between two groups in general clinical data, such as gender ratio, gestational age, birth weight, 1 and 5 min Apgar scores, rate of surfactant administration, the age of commencement of oral medication, and rates of administration of dexamethasone for promoting fetal lung maturity before labor, cesarean section and the duration of premature rupture of membranes more than 18 h of pregnant mother (P>0.05). This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

①The rate of closure of ductus arteriosus was 56.6% (30/53) in extreme premature neonates of ibuprofen group, which was statistically higher than that of paracetamol group 30.2% (13/43), and the difference was statistically significant (χ²=6.676, P=0.009). After oral medication, the inner diameter of ductus arteriosus in ibuprofen group was (0.14±0.26) cm, which was significantly shorter than that of paracetamol group (0.30±0.14) cm, and the difference was also statistically significant (t=-5.406, P=0.007). ②There were no differences between two groups in time to full enteral feeding and duration of invasive mechanical ventilation (P>0.05). ③There were no differences between two groups in incidence of liver injury, kidney injury, hyperbilirubinemia, thrombocytopenia, anemia, gastrointestinal bleeding, pulmonary hemorrhage, intraventricular hemorrhage (IVH), early-onset sepsis (EOS), late-onset sepsis (LOS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), failure of oral medication and transfer to surgery or mortality of neonates (P>0.05).

The safety of oral treatment by ibuprofen in extreme premature neonates with hsPDA is similar to that of paracetamol. The efficacy of oral treatment by ibuprofen is superior to that of paracetamol. Since this study is just a single-center study and sample size is relatively small, efficacy and safety of oral treatment by ibuprofen and paracetamol in extreme premature neonates with hsPDA still needs to be further confirmed by large-sample size, multi-center and randomized controlled trials.