Huang Wenrui, Yu Yue, Chen Lei, Tang Xiaoxuan, Fang Xingzi, Ou Xingyan, Du XueLian
Guangzhou University of Chinese Medicine, Guanzhou, Guangdong, China (Huang, Yu, Chen, Tang, Fang, and Ou); Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China (Huang, Chen, Tang, Fang, Ou, Du).
Guangzhou University of Chinese Medicine, Guanzhou, Guangdong, China (Huang, Yu, Chen, Tang, Fang, and Ou).
Am J Obstet Gynecol MFM. 2025 Feb;7(2):101572. doi: 10.1016/j.ajogmf.2024.101572. Epub 2024 Nov 26.
To assess the effectiveness and safety of low molecular weight heparins (LMWHs) on live birth rates and adverse pregnancy outcomes in individuals experiencing recurrent spontaneous abortion (RSA).
PubMed, Web of Science, the Cochrane Library, and Embase from database inception to July 1, 2024.
Eligible randomized controlled trials enrolled women with RSA who received LMWH, with a follow-up duration of at least 12 weeks. The treatment was either monotherapy with LMWH or added LMWH to nonrandomized background anticoagulant treatments, with the control group being placebo and other anticoagulant treatments. Trials with a crossover design or involving withdrawn drugs were also excluded.
We assessed bias using the Risk of Bias 2.0 tool and evaluated evidence quality with the Confidence in Network Meta-Analysis framework. The network meta-analysis employed a Bayesian framework to integrate direct and indirect evidence, calculating risk ratios and 95% confidence intervals. Markov chain Monte Carlo methods generated posterior distributions, allowing comparison and ranking of treatments. Subgroup, regression, and sensitivity analyses assessed the impact of various factors on the results.
This network meta-analysis included 22 trials involving 4773 participants across five different LMWH drugs, with all comparisons made against the control group. Among the five drugs, enoxaparin showed significant benefits. It notably improved live birth rates (LBR) (Risk Ratios 1.19, (95% confidence intervals 1.06 to 1.36), surface under the cumulative ranking curve 73%; moderate confidence of evidence), reduced the risk of pre-eclampsia (0.53, (0.28-0.92), 85%), lowered preterm delivery (0.59, [0.41-0.86], 85%), and decreased pregnancy loss (0.55, [0.38-0.76], 82%). Further analysis of 7 different LMWH doses revealed that both enoxaparin 20mg (1.53, [1.08-2.25], 89%) and 40mg (1.18, [1.04-1.38], 59%) significantly improved LBR, with the 20mg dose proving more effective. Both doses also significantly reduced the risk of pregnancy loss.
Enoxaparin proved to be the most effective LMWH in increasing LBR compared to the control group. It also significantly lowered the risks of pre-eclampsia, preterm delivery, and pregnancy loss. A dosage-based subgroup analysis showed that both 20mg and 40mg of enoxaparin improved LBR, with the 20mg dose demonstrating greater effectiveness. El resumen está disponible en Español al final del artículo.
评估低分子量肝素（LMWHs）对复发性自然流产（RSA）患者活产率及不良妊娠结局的有效性和安全性。
从数据库建立至2024年7月1日的PubMed、Web of Science、Cochrane图书馆和Embase。
符合条件的随机对照试验纳入接受LMWH治疗的RSA女性，随访时间至少12周。治疗方式为LMWH单药治疗或在非随机背景抗凝治疗基础上加用LMWH，对照组为安慰剂和其他抗凝治疗。交叉设计或涉及撤药的试验也被排除。
我们使用偏倚风险2.0工具评估偏倚，并采用网状Meta分析框架中的证据置信度评估证据质量。网状Meta分析采用贝叶斯框架整合直接和间接证据，计算风险比和95%置信区间。马尔可夫链蒙特卡罗方法生成后验分布，以便对治疗进行比较和排序。亚组分析、回归分析和敏感性分析评估了各种因素对结果的影响。
该网状Meta分析纳入了22项试验，涉及5种不同LMWH药物的4773名参与者，所有比较均与对照组进行。在这5种药物中，依诺肝素显示出显著益处。它显著提高了活产率（LBR）（风险比1.19，[95%置信区间1.06至1.36]，累积排序曲线下面积73%；证据置信度中等），降低了子痫前期风险（0.53，[0.28 - 0.92]，85%），降低了早产风险（0.59，[0.41 - 0.86]，85%），并降低了妊娠丢失风险（0.55，[0.38 - 0.76]，82%）。对7种不同LMWH剂量的进一步分析表明，依诺肝素20mg（1.53，[1.08 - 2.25]，89%）和40mg（1.18，[1.04 - 1.38]，59%）均显著提高了LBR，其中20mg剂量更有效。两种剂量还均显著降低了妊娠丢失风险。
与对照组相比，依诺肝素被证明是增加LBR最有效的LMWH。它还显著降低了子痫前期、早产和妊娠丢失的风险。基于剂量的亚组分析表明，20mg和40mg的依诺肝素均改善了LBR，其中20mg剂量显示出更大的有效性。文章末尾提供了西班牙语摘要。
