Low-molecular-weight Heparin For The Prevention And Treatment Of Hypertensive Disorders In Pregnancy:a Systematic Review And Meta-analysis

Background and ObjectiveHypertensive disorders complicating pregnancy is a group of diseases in which pregnancy and hypertension coexist,with an incidence of about 5%-12%^[1].Seriously affecting maternal and child health,leading to the rise in maternal and perinatal mortality.Giannubilo^[2]reported that the pre-eclampsia patients had a recurrence rate of 10%-65%,compared with the normal pregnancy population,the risk of re-pregnancy recurrence in the high-risk group with previous pre-eclampsia increased by 7 times.Therefore,research on preventing the recurrence of hypertensive disorder complicating pregnancy is a hot issue and a very challenging problem to be solved.In the related research on prevention and treatment of hypertensive disorders complicating pregnancy,various preventive measures such as supplementation of vitamins C and E,control of body weight during pregnancy,supplementation of calcium,adjustment of diet and lifestyle,and anticoagulant drugs were proposed.The therapeutic effects are different,especially the use of anticoagulant drugs such as low molecular weight heparin.Some studies have shown that endogenous heparin deficiency in patients with hypertensive disorder complicating pregnancy,serum heparin and anticoagulant activity is reduced by 50%compared with normal pregnant women^[3].Rodger^[4]has pointed out that the use of low molecular weight heparin does not reduce the risk of important adverse pregnancy outcomes such as venous thrombosis,fetal growth restriction,abortion,and preeclampsia in pregnant women.The question of which phase of anticoagulant drug to start taking,the dose,the combination of aspirin or the single use in the pregnancy remains to be resolved.The study collected recent studies on low molecular weight heparin in the prevention and treatment of hypertensive disorder complicating pregnancy,and Meta-analysis of experimental data in the literature to provide evidence-based evidence for the clinical application value of low molecular weight heparin in the prevention and treatment of hypertensive disorder complicating pregnancy.MethodComputer search in PubMed,EMbase,Cochrane Library,WHO International Clinical Trial Registration Platform（ICTRP）and ClinicalTrials.gov,web of science,CBM,CNKI,Wanfang Database,and VIP,supplemented by manual search.Collect randomized controlled trials of LMWH for the prevention and treatment of hypertensive disorder complicating pregnancy and extract valid data.Research indicators mainly include hypertensive disorders of pregnancy,fetal growth restriction,placental abruption,neonatal mortality,neonatal birth weight,postpartum hemorrhage,osteoporosis,thrombocytopenia,allergies and so on.The two reviewers independently extract the data,and different opinions were resolved through discussion.All data were statistically analyzed in the RevMan version 5.3.ResultsFinally,11 studies containing 4 high quality RCTs were included.Meta analyzed9 of the subjects,which included 1140 subjects（LMWH group 571 vs control group569）.In the main research indicators,LMWH reduced the recurrence rate of the main composite outcomes（OR=0.43,95%CI=[0.28,0.66],P<0.001）,and the recurrence rate of hypertensive disorder complicating pregnancy（OR=0.58,95%CI=[0.41,0.83],P=0.003）,fetal growth restriction（OR=0.63,95%CI=[0.44,0.89],P=0.008）,neonatal mortality（OR=0.25,95%CI=[0.07,0.82],P=0.02）,prolonged gestational weeks of pregnancy（MD=0.75,95%CI=[0.18,1.33],P=0.01）;In terms of LMWH safety,there was no statistically significant difference in postpartum hemorrhage,osteoporosis and thrombocytopenia.Allergic reactions after treatment（OR=10.89,95%CI=[1.32,90.05],P=0.03）were statistically significant;Among the secondary indicators,LMWH was statistically significant in the prevention of early-onsetpre-eclampsia（OR=0.32,95%CI=[0.12,0.83],P=0.02）,no thrombophilia（OR=0.38,95%CI=[0.18,0.77],P=0.008）and fetal growth restriction（OR=0.64,95%CI=[0.44,0.93],P=0.02）;In the comparison of the efficacy of LMWH combined with ASA and ASA or LMWH alone,ASA alone group（OR=0.51,95%CI=[0.32,0.80],P<0.05）was statistically significant,and the LMWH alone group（OR=0.28,95%CI=[0.17,0.46],P<0.05）was also statistically significant.Conclusions1.LMWH is safe and effective for the prevention and treatment of hypertensive disorder complicating pregnancy;2.The combination of LMWH and ASA has better control effect than LMWH or ASA alone.