小剂量阿司匹林联合肝素预防子痫前期疗效的Meta分析

目的:评价妊娠16周前使用小剂量阿司匹林联合肝素预防子痫前期的疗效及安全性。方法:计算机检索PubMed、CochraneLibrary、MEDLINE、EMbase、CNKI、维普、中国生物医学文献服务系统、万方数据库,检索时限为2002年1月至2019年1月。选择对存在子痫前期高危因素的孕妇在16周前预防性使用阿司匹林及阿司匹林联合肝素的随机对照试验(RCT),筛选出符合纳入标准的文献,并进行质量评价,利用Cochrane协作网提供的RevMan5.3软件对小剂量阿司匹林联合肝素预防子痫前期疗效进行Meta分析。结果:根据上述方法共纳入8篇RCT试验,Meta分析结果显示:与单独使用阿司匹林相比,阿司匹林联合使用肝素可降低子痫前期发生率(RR0.69,95%CI0.50~0.96,P=0.03),提高活产率(RR1.05,95%CI1.01~1.10,P=0.02),两组小于孕龄儿、早产、胎盘早剥、产后出血及早发型子痫前期的发生率差异无统计学意义(RR0.74,95%CI0.54~1.00,P=0.05;RR0.91,95%CI0.72~1.14,P=0.42;RR0.72,95%CI0.27~1.87,P=0.50;RR0.94,95%CI0.54~1.66,P=0.84;RR0.63,95%CI0.31~1.26,P=0.19)。阿司匹林联合肝素可降低抗磷脂抗体阴性组子痫前期发生率(RR0.67,95%CI0.46~0.96,P=0.03)。结论:妊娠16周前联合使用阿司匹林及肝素相比于单独使用阿司匹林可有效预防子痫前期发生,提高活产率,不会增加其他不良妊娠结局发生,且对于抗磷脂抗体阳性及阴性孕妇作用有所差别,但尚需要国内外大样本、多中心的研究文献来证实其临床应用价值。

Prevention of Pre-eclampsia by Heparin in Addition to Low-dose Aspirin:A Meta-analysis

Objective: To evaluate the efficacy and safety of heparin in addition to low-dose aspirin for prevention of pre-eclampsia started≤16 weeks' gestation.Methods: A systematic review and meta-analysis of randomized controlled trials published since January 2002 until January 2019 was performed by searching the medical data- bases form PubMed,Cochrane Library,MEDLINE,EMbase,CNKI,VIP,SinoMed and WanFang.Pregnant women with high risks of developing pre-eclampsia are randomized to receive low-dose aspirin alone or heparin in addi- tion to low-dose aspirin.The revman 5. 3 software was used for Meta-analysis.Outcome measures were rates of pre-eclampsia,early onset pre-eclampsia,prematurity and small for gestational age babies,live birth rate and so on.Results: Eight RCTs met the inclusion criteria.Treatment with heparin in addition to low-dose aspirin,compared with low-dose aspirin alone,shows a significant reduction in development of pre-eclampsia ( RR 0. 69,95% CI 0. 50-0. 96,P = 0. 03) and higher live birth rates( RR 1. 05,95%CI 1. 01-1. 10,P = 0. 02).No significant differences were observed between two groups for rates of small for gestational age babies,prematurity,placental ab- ruption,postpartum hemorrhage and early onset pre-eclampsia( RR 0. 74,95%CI 0. 54-1. 00,P=0. 05;RR 0. 91,95%CI 0. 72-1. 14,P=0. 42;RR 0. 72,95%CI 0. 27-1. 87,P = 0. 50;RR 0. 94,95%CI 0. 54-1. 66,P = 0. 84;RR 0. 63,95%CI 0. 31-1. 26,P=0. 19).Subgroup analysis shows using heparin in addition to low-dose aspirincan re- duce the prevalence of pre-eclampsia significantly for the antiphospholipid antibody-negative subgroup( RR 0. 67, 95%CI 0. 46-0. 96,P=0. 03).Conclusions: Based on presentevidence,the addition of heparin to low-dose aspirin started≤16 weeks' gestation could reduce the prevalence of pre-eclampsia and improve the live birth rate without increasing rates of other harmful outcomes.And there is a difference in the efficacy between antiphospholipid anti- body-positive and negative subgroups.But more home and abroad large sample size and multi-center randomized controlled trials are required to further demonstrate and support the conclusion.