Meta-analysis Of Low-molecular-weight Heparin To Prevent Recurrent Placenta-mediated Pregnancy Complications

Objective:We performed a meta-analysis of randomized controlled trials(RCTs)assessing the efficacy on prevention of recurrent placenta-mediated pregnancy complications(PMPC)by using low-molecular-weight heparin(LMWH)alone.Moreover,to make sure if the efficacy of LMWH can be strengthened when it is used in combination with aspirin.We sought to obtain more objective and comprehensive evidence so as to provide valuable evidence-based basis for clinical medication.Methods:In this meta-analysis,China National Knowledge Infrastructure(CNKI),Wanfang,PubMed,Cochrane library were searched to identify all relevant articles on the recurrence of PMPC published from December 2018 onwards,publications were also sought through a hand search of references and conference papers in the literature.Two independent reviewers screened the literature according to the inclusion criteria,assessed quality and extracted relevant data after checking duplicates.The network meta-analysis was performed using Revman5.3 software and STATA version 12.0.The summary measures were reported as relative risk(RR)and weighted mean differences(WMD)with 95% confidence interval(CI).In addition,publication bias was evaluated by performing Egger checkout and observing the symmetry characteristics shown in funnel plots,to explore sensitivity and stability of the effects.Results:A final total of 15 RCTs with 2243 patients was included in the present analysis,Which is divided into two subgroups.One group is for the LMWH vs no anticoagulant,recruiting of 1271 patients.The other accounts for LMWH vs combination of LMWH and aspirin,recruiting of 972 patients.Incidence of preeclampsia,fetal growth restriction,placental abruption(PA),postpartum hemorrhage and neonatal birth weight were considered as primary outcomes,to investigate the efficacy and safety of LMWH for prevention on the recurrence of placenta-mediated pregnancy complications.Results: 1.LMWH vs no anticoagulant,the incidence of preeclampsia [RR=0.36,95%CI(0.27,0.48),P<0.001],the incidence of fetal growth restriction [RR=0.37,95%CI(0.25,0.53),P<0.001],the incidence of PA [RR=0.35,95%CI(0.18,0.69),P=0.002<0.05],the comparison of neonatal birth weight [WMD=377.71,95%CI(179.57,575.84),P=0.0002<0.05],the overall results suggested that there were significant differences between LMWH and no anticoagulant group.It demonstrated that LMWH was associated with better efficacy than no anticoagulant group for the recurrence of PMPC so as to benefit the pregnancy outcome.2.In our primary outcome analysis,LMWH vs combination of LMWH and aspirin,the incidence of preeclampsia [RR=0.72,95%CI(0.47,1.1),P=0.13>0.05],the incidence of fetal growth restriction [RR=0.75,95%CI(0.53,1.06),P=0.10>0.05],the incidence of PA [RR=1.05,95%CI(0.46,2.39),P=0.91>0.05],the comparison of neonatal birth weight [WMD=149.84,95%CI(-61.15,360.83),P=0.16>0.05],no obvious difference was observed between the two groups according to the above results.Collectively,it showed that the combination of LMWH and aspirin did not reduce the recurrence of PMPC effectively compared with LMWH alone.3.When evaluating outcomes in the subgroup of LMWH vs combination of LMWH and aspirin,there was no significant difference in the incidence of postpartum hemorrhage between the two groups([RR=0.6,95%CI(0.27,1.34),P=0.21>0.05]?[RR=0.97,95%CI(0.66,1.43),P=0.88>0.05]),it indicated that LMWH demonstrated no effect on the incidence of postpartum hemorrhage.Conclusion: 1.LMWH appears to significantly reduce the risk of recurrent PMPC so as to benefit the pregnancy outcome.2.No association was found for the effect of combination of LMWH and aspirin in reducing the recurrence of PMPC compared to LMWH alone.3.LMWH appears to be a promising preventative therapy to prevent recurrent PMPC for the patients with aspirin contraindication or intolerance.4.Our meta-analysis similarly demonstrated that no effect on the incidence of postpartum hemorrhage was found by using LMWH.