Comparative effectiveness of Low Molecular Weight Heparin on Live birth for Recurrent Spontaneous Abortion: systematic review and network meta-analysis: Effectiveness of LMWH on Live Birth in RSA.

Abstract

Objective: 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).

Data sources: PubMed, Web of Science, the Cochrane Library, and Embase from database inception to July 1, 2024.

Study eligibility criteria: Eligible randomised 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 non-randomised 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 Trials with a crossover design or involving withdrawn drugs were also excluded.

Study appraisal and synthesis methods: 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.

Results: This network meta-analysis included 22 trials involving 4,773 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 seven 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.

Conclusion: 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.