静脉预防性应用布洛芬对早产儿动脉导管未闭影响的meta分析

Meta-analysis of the effect of intravenous prophylactic ibuprofen on prevention of patent ductus arteriosus in preterm infants

目的评价早产儿静脉预防性应用布洛芬对动脉导管未闭（patent ductus arteriosus，PDA）的有效性及安全性。方法计算机检索PubMed、ScienceDirect、EMBASE、OVID、Cochrane图书馆、维普中文科技期刊数据库、中国学术期刊网全文数据库，并手工检索作为补充，收集静脉预防性应用布洛芬对早产儿PDA影响的随机对照试验（randomized controlled trial，RCT）并进行筛选和质量评价，采用RevMan5．0．21软件进行meta分析，计量资料采用加权均数差（weighted mean difference，WMD）及其95％CI表示，计数资料采用相对危险度（riskratio，RR）及其95％CI表示。结果最终纳入文献4篇，其中3篇文献Jadad评分为4分，1篇文献为3分。Meta分析结果示：（1）静脉预防性应用布洛芬可以减少早产儿第3天动脉导管未关闭的风险（RR=0．40，95％CI：0．31～0．51，P〈0．01）、需环氧酶抑制剂再治疗以关闭动脉导管（RR=0．18，95％CI：0．07～0．45，P=0．0003）及需外科结扎以关闭动脉导管（RR=0．34，95％CI：0．14～0．81，P=0．02）。（2）就目前数据而言，本meta分析未发现静脉预防性应用布洛芬对早产儿肺、脑、胃肠、肾等系统产生显著不良影响。结论早产儿静脉预防性应用布洛芬可显著减少生后第3天动脉导管未关闭、需环氧酶抑制剂再治疗以关闭动脉导管和外科结扎关闭动脉导管，且短期内未见明显不良影响，但现有证据尚不足以推荐临床静脉预防性应用布洛芬防治早产儿PDA。

Objective To determine the effectiveness and safety of prophylactic intravenous ibuprofen compared to placebo/no intervention on the prevention of patent ductus arteriosus（PDA） in preterm infants. Methods Randomized controlled trials（RCT） or quasi-RCT comparing prophylactic intravenous ibuprofen versus placebo/no treatment for prevention of PDA in preterm infants were enrolled. The standard search strategy included electronic search and manual search. Electronic search was carried out in databases including PubMed, ScienceDirect, EMBASE, OVID, Cochrane Library, VIP Chinese Periodical Database and Chinese Digital Hospital Library （www. chkd. cnki. net） without language restriction. As a supplementation, references in previous reviews and studies identified as relevant had been examined by manual search. RevMan 5.0.21 was used in the statistical analysis. Effects were expressed as weighted mean difference （WMD） and 95% confidence interval （C1） for continuous data while risk ratio （RR） and 95 %CI for categorical data. Results Four studies qualified for this meta analysis including three graded 4 and one graded 3 with Jadad scale. Prophylactic use of ibuprofen significantly decreased the incidence of PDA on day three （RR 0.40, 95 % CI： 0.31 0. 51, P〈0.01 ）, the need for rescue treatment with cyclo-oxygenase inhibitors （RR = 0. 18, 95%CI：0.07-0.45,P 0.0003） and the need for surgical ligation （RR=0. 34,95%CI：0. 14 0.81,P= 0. 02） in the prophylactic group. No significant difference of pulmonary, cerebral, gastrointestinal, and renal complications were found between the prophylactic and control groups. Conclusions Prophylactic intravenous ibuprofen significantly reduces the risk of PDA on day three, decreases the need for rescue treatment with cyelcroxygenase inhibitors and surgical ligation without significant pulmonary, cerebral, gastrointestinal, and renal complications were seen in the prophylactic group. Due to the limits of evidences to date, prophylactic ibuprofen intravenously for prevention of PDA in preterm infants is not recommended.