低分子肝素预防子痫前期及其并发症的Meta分析

Low-molecular-weight heparin for preventing pre-eclampsia and its complications: A Meta-analysis

目的:分析评价对子痫前期(PE)高危妊娠妇女预防性应用低分子肝素(LMWH)的疗效及安全性。方法:检索PubMed、The Cochrane Library、Embase、CBM和CNKI等数据库,选择对PE高危妊娠妇女预防性应用LMWH的随机对照研究(RCTs),应用修改后Jadad量表进行质量评价,Stata12.0软件进行Meta分析。结果判定指标用相对危险度(RR)或标准化均数差(SMD)及其95%可信区间(95%CI)表示。结果:共纳入6篇RCTs,其中5篇为高质量文献,分成LMWH组(525例)与LMWH联合阿司匹林(ASA)组(363例)两个亚组。LMWH组与LMWH联合ASA组的Meta分析结果显示,对PE高危人群预防性应用LMWH可减少PE(6项研究888例,RR=0.34,95%CI为0.21～0.56和RR=0.53,95%CI为0.30～0.91)、5min Apgar评分<7分(3项研究519例,RR=0.51,95%CI为0.32～0.83和RR=0.33,95%CI为0.18～0.57)、胎儿宫内生长受限(6项研究848例,RR=0.34,95%CI为0.21～0.55和RR=0.52,95%CI为0.31～0.89)、新生儿入住监护病房(3项研究494例,RR=0.52,95%CI为0.28～0.97和RR=0.37,95%CI为0.19～0.69)的发生率,适度增加出生体重、延长孕周,差异均有显著统计学意义(P<0.05)。但对胎盘早剥、HELLP综合征、早产、胎死宫内与新生儿死亡方面无显著效果,且无增加产时出血风险。结论:LMWH预防PE及其并发症具有一定的疗效,临床应用安全,但仍需大样本、多中心的双盲RCTs以进一步证实其优越性。

Objective：To assess the effectiveness and safety of low-molecular-weight heparin （ LMWH ） for women at risk of developing pre-eclampsia. Methods：We searched PubMed,The Cochrane Library,Embase,CBM,CNKI. All randomized trials comparing LMWH with either placebo or no antiaggregant were included. Participants were pregnant women at risk of developing pre-eclampsia. RCTs were assessed based on the Jadad assessment,the data were analyzed by using Stata12. 0 software. The results were stated as relative risk（RR）or Standardized mean difference （ SMD） ,with a 95 % confidence interval（ CI） . Results：Six trials（888 cases）are included,Divided into two subgroups to meta analysis,LMWH group（525 cases） and LMWH combinate aspirin group （ 363 cases ） , which results show that LMWH was associated with a statistically significant reduction in the relative risk of pre-eclampsia[6 studies,888 cases,RR=0. 34,95%CI（0. 21,0. 56）and RR=0. 53,95%CI（0. 30,0. 91）],5thminuteˊs Apgar score 〈7[3 studies,519 cases,RR=0. 51,95%CI（0. 32,0. 83） and RR=0. 33,95%CI （0. 18,0. 57）];fetal growth restriction[6 studies,848 cases,RR=0. 34,95%CI（0. 21,0. 55） and RR=0. 52,95%CI（0. 31,0. 89）],NICU admission[3 studies,494 cases,RR=0. 52,95%CI（0. 28,0. 97） and RR=0. 37,95%CI（0. 19,0. 69）],birth weight and gestational age. But there were no statistically significant differences in placental abruption,HELLP syndrome,preterm birth,haemoglobin,foetal loss after 20 weeks and fetal death. Conclusion：Low-molecularweight heparin have moderate benefits when used for preve-ntion of pre-eclampsia and its consequences. But rigorously designed large sample size randomized double blind clinical trials are required to further demonstrate and support the conclusion.