Low-molecular-weight heparin for prevention of preeclampsia and other placenta-mediated complications: a systematic review and meta-analysis

Abstract

BACKGROUND: Evidence on the impact of low-molecular-weight heparin, alone or in combination with low-dose aspirin, for the prevention for preeclampsia in high-risk patients is conflicting. OBJECTIVE: We conducted a meta-analysis of studies published to assess the effectiveness of low-molecular-weight heparin for the prevention of preeclampsia and other placenta-related complications in high-risk women. DATA SOURCES: A systematic search was performed to identify relevant studies, using the databases PubMed and Cochrane Central Register of Controlled Trials, without publication time restrictions. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing treatment with lowmolecular-weight heparin or unfractionated heparin (with or without low-dose aspirin), in highrisk women, defined as either history of preeclampsia, intrauterine growth restriction, fetal demise, or miscarriage or being at high risk after first-trimester screening of preeclampsia. STUDY APPRAISAL AND SYNTHESIS METHODS: The systematic review was conducted according to the Cochrane Handbook guidelines. The primary outcome was the development of preeclampsia. We performed prespecified subgroup analyses according to combination with low-dose aspirin, low-molecular-weight heparin type, gestational age when treatment was started, and study population (patients with thrombophilia, at high risk of preeclampsia or miscarriage). Secondary outcomes included small for gestational age, perinatal death, miscarriage, and placental abruption. Pooled odds ratios with 95% confidence intervals were calculated using a random-effects model. Quality of evidence was assessed using the grading of recommendations assessment, development, and evaluation methodology. RESULTS: A total of 15 studies (2795 participants) were included. In high-risk women, treatment with low-molecular-weight heparin was associated with a reduction in the development of preeclampsia (odds ratio, 0.62; 95% confidence interval, 0.43e0.90; P¼.010); small for gestational age (odds ratio, 0.61; 95% confidence interval, 0.44e0.85; P¼.003), and perinatal death (odds ratio, 0.49; 95% confidence interval, 0.25e0.94; P¼.030). This reduction was stronger if low-molecular-weight heparin was started before 16 weeks' gestation (13 studies, 2474 participants) for preeclampsia (odds ratio, 0.55; 95% confidence interval, 0.39e0.76; P¼.0004). When only studies including low-dose aspirin as an intervention were analyzed (6 randomized controlled trials, 920 participants), a significant reduction was observed in those with combined treatment (low-molecularweight heparin plus low-dose aspirin) compared with low-dose aspirin alone (odds ratio, 0.62; 95% confidence interval, 0.41e0.95; P¼.030). Overall, adverse events were neither serious nor significantly different. Quality of evidence ranged from very low to moderate, mostly because of the lack of blinding, imprecision, and inconsistency. CONCLUSION: Low-molecular-weight heparin use was associated with a significant reduction in the risk of preeclampsia and ot...

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

“…One meta-analyses found that the combination of LMWH and low-dose aspirin significantly reduced the risk of preeclampsia compared with low-dose aspirin alone. 106 Specific PAI-1 inhibitors have been developed to target high PAI-1 plasma levels but so far none are approved for therapeutic use in humans. 107 Further studies should be performed on PAI-1 plasma levels in a prospective design to determine the clinical relevance of high PAI-1 plasma levels in placenta-mediated pregnancy complications.…”

Ferroptosis and Its Emerging Role in Pre-Eclampsia

“…Additionally, studies have showed that aspirin treatment at 150 mg per day reduced preterm PE by 62% when compared to the placebo [ 172 ]. Low-dose aspirin is now recommended for PE prevention in high-risk women, although there is currently a dearth of conclusive evidence proving how aspirin treatment reduces prenatal morbidity and death [ 173 ]. Studies have also shown that, in high-risk women, the initiation of treatment with low-molecular-weight heparin before 16 weeks of gestation can significantly reduce the risk of PE and other placenta-mediated complications.…”

Sinn und Nutzen des Präeklampsiescreenings im 1. Trimenon

“…Die Datenlage zum potenziell präventiven Effekt von Heparin ist sehr heterogen, neueren Studienergebnissen zufolge könnte NMH einen günstigen Effekt in der Prävention der PE bzw. plazentamediierter Schwangerschaftskomplikationen zeigen [40,41]. Prinzipiell gilt auch die Anwendung von Heparin in der Schwangerschaft als sicher [1].…”