【摘要】 目的系统评价低分子肝素在妊娠期使用的安全性。方法计算机检索PubMed、EMbase、The Cochrane Library、Wan Fang Data、VIP和CNKI数据库,搜集低分子肝素用于妊娠期安全性的随机对照试验(RCT)和队列研究,检索时限均为建库至2021年3月30日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果共纳入77个RCT和13个队列研究。Meta分析结果显示:使用低分子肝素可能增加产后出血发生率[RR=1.50,95%CI(1.00,2.25),P=0.05],但两组差异无统计学意义。血液系统不良事件发生率RCT和队列研究结果不同。RCT的亚组分析结果显示低分子肝素增加注射部位瘀斑发生率[RR=1.60,95%CI(1.24,2.08),P=0.000 4],但皮肤系统总体不良事件发生率未明显增加;低分子肝素减少心血管系统不良事件发生率[RR=0.18,95%CI(0.07,0.46),P=0.000 3];未显著增加胎儿先天畸形、消化系统、中枢神经系统、骨骼系统、全身不良事件发生。结论当前证据显示,低分子肝素在妊娠期使用安全性较高,但是否增加产后出血、血液系统不良反应尚不明确。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。更多还原

【Abstract】 Objective To systematically review the safety of low molecular weight heparin(LMWH) in pregnancy. Methods PubMed, EMbase, The Cochrane Library, WanFang Data, VIP, and CNKI databases were electronically searched to collect randomized controlled trials(RCTs) and cohort studies on the safety of LMWH in pregnancy from inception to March 30 th, 2020. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 77 RCTs and 13 cohort studies were included. The results of meta-analysis showed that LMWH increased the incidence of postpartum hemorrhage(RR=1.50, 95%CI 1.00 to 2.25, P=0.05). However, there was no significant difference.The incidence of hematological adverse events was different from the results of RCTs and cohort studies. The results of RCT subgroup analysis showed that LMWH increased ecchymosis at the injection site(RR=1.60, 95%CI 1.24 to 2.08,P=0.000 4). However, the incidence of overall skin system adverse events did not increase significantly. LMWH reduced the incidence of cardiovascular adverse events(RR=0.18, 95%CI 0.07 to 0.46, P=0.000 3). LMWH failed to increase the occurrence of fetal congenital malformations, digestive system, central nervous system, skeletal system, and systemic adverse events. Conclusions Current evidence suggests that LMWH is relatively safe to use during pregnancy. However,whether it increases postpartum hemorrhage and hematological adverse events is unclear. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.更多还原