Aspirin, low molecular weight heparin, or both in preventing pregnancy complications in women with recurrent pregnancy loss and factor V Leiden mutation

Karadağ, Cihan; Akar, Bertan; Gönenç, Gökçenur; Aslancan, Reyhan; Yılmaz, Nagihan; Çalışkan, Eray

doi:10.1080/14767058.2019.1671348

Cited by 14 publications

(36 citation statements)

References 35 publications

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“…Analysis for previous PE as inclusion criteria before 16 weeks' gestation (9 studies, 1405 participants) 22,23,39,41,42,45e47,49 showed a 40% reduction on the incidence of recurrent PE (OR, 0.60; 95% CI, 0.39e0.93; P¼.020; I 2 ¼31%) (Figure 5). When studies were divided by inclusion (4 studies, 580 participants) 39,43,49,50 or exclusion (8 studies, 1482 participants) 22,38,40e42,44,46,47 of patients with thrombophilia, the effect of LMWH on occurrence of PE was nonsignificant in thrombophilic patients vs patients without thrombophilia (P¼.470) (Figure 6). Analysis for studies with miscarriage as inclusion criteria (3 studies, 809 participants) 38,43,48 showed no significant effect of LMWH on the incidence of PE (OR, 0.60; 95% CI, 0.29e1.23, P¼.160; I 2 ¼0%) (Supplemental Figure 1).…”

Section: Synthesis Of Resultsmentioning

confidence: 99%

“…When studies were divided by inclusion (4 studies, 580 participants) 39,43,49,50 or exclusion (8 studies, 1482 participants) 22,38,40e42,44,46,47 of patients with thrombophilia, the effect of LMWH on occurrence of PE was nonsignificant in thrombophilic patients vs patients without thrombophilia (P¼.470) (Figure 6). Analysis for studies with miscarriage as inclusion criteria (3 studies, 809 participants) 38,43,48 showed no significant effect of LMWH on the incidence of PE (OR, 0.60; 95% CI, 0.29e1.23, P¼.160; I 2 ¼0%) (Supplemental Figure 1). When analyses by type of LMWH were performed, we found that both enoxaparin and dalteparin were each associated with a significant reduction in PE, with no statistical differences between them (enoxaparin, 7 RCTs, 22,23,38,40e43 1532 participants; OR, 0.58; 95% CI, 0.39e0.87; P¼.008; I 2 ¼20%; dalteparin, 6 RCTs, 39,46e50 1103 participants; OR, 0.50; 95% CI, 0.25e0.97; P¼.040; I 2 ¼36%) (Figure 7).…”

Section: Synthesis Of Resultsmentioning

confidence: 99%

“…No statistically significant differences were found in terms of the occurrence of HELLP syndrome between LMWH-treated and nontreated patients (8 RCTs, 1243 participants; OR, 0.65; 95% CI, 0.27e1.56; P¼.340; I 2 ¼0%) (Supplemental Figure 8). Notably, 7 RCTs recorded the outcome 22,23,39,42,43,45,49 One study 43 reported 3 episodes of eclampsia, 1 in the LMWH group and 2 in the nontreated group; 3 studies 23,42,48 reported maternal mortality as an outcome, with no events in either group.Adverse events. No statistically significant difference in bleeding was found between LMWH-treated and nontreated patients, regardless of whether or not LMWH was combined with LDA (10 RCTs, 2109 participants; OR, 1.14; 95% CI, 0.75e1.71; P¼.540; I 2 ¼8%) (Figure 9).…”

Section: Synthesis Of Resultsmentioning

confidence: 99%

“…Overall, methodological quality ranged from moderate to very low owing to concerns about the risk of bias (blinding was not possible in most trials because of the intervention, ie, subcutaneous injection of LMWH), the small number of events for many outcomes, lack of details about important methodological issues in some studies, substantial heterogeneity detected in the analyses, and wide CIs indicating imprecision in the results. All trials, except 2, 38,43 were considered as high risk of bias owing to lack of blinding, but even for these with unclear risk of bias, it was unlikely to have occurred. Methodological quality assessment for each individual study, risk of bias graph, ajog.org Systematic Review risk of bias graph summary, and publication bias funnel plot can be found in the Supplemental Material.…”

Section: Risk Of Bias Of Included Studiesmentioning

confidence: 99%

“…53 In a previous meta-analysis, there was a high variability among studies and the need for multicenter clinical studies for further research and confirmation has been recognized. Recently, a number of new randomized trials have been published (heparin-preeclampsia, 42 enoxaparin for the prevention of preeclampsia and intrauterine growth restriction, 23 Karada g et al, 43 FRUIT-II, 49 and HOPPE 22 trials). In our metaanalysis, a total of 15 studies (2848 participants) were reviewed.…”

Section: Comparison With Existing Literaturementioning

confidence: 99%

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

Cruz‐Lemini

Vázquez

Ullmo

et al. 2022

American Journal of Obstetrics and Gynecology

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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...

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Section: Synthesis Of Resultsmentioning

confidence: 99%

Section: Synthesis Of Resultsmentioning

confidence: 99%

Section: Synthesis Of Resultsmentioning

confidence: 99%

Section: Risk Of Bias Of Included Studiesmentioning

confidence: 99%

Section: Comparison With Existing Literaturementioning

confidence: 99%

See 3 more Smart Citations

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

Cruz‐Lemini

Vázquez

Ullmo

et al. 2022

American Journal of Obstetrics and Gynecology

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Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta‐Analysis

Bettiol

Avagliano

Lombardi

et al. 2021

Clin Pharma and Therapeutics

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The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials. gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/-LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.Fetal growth restriction (FGR) is a relatively common pregnancy complication and is usually defined based on the discrepancy between actual and expected fetal ultrasound biometric measurements for a given gestational age. 1 Fetuses with FGR do not achieve the genetically predetermined growth potential as a result of maternal (e.g., undernutrition, exposure to toxins,

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La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français

Sentilhes,

Schmitz,

Arthuis

et al. 2024

Gynécologie Obstétrique Fertilité & Sénologie

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Aspirin, low molecular weight heparin, or both in preventing pregnancy complications in women with recurrent pregnancy loss and factor V Leiden mutation

Cited by 14 publications

References 35 publications

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

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

Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta‐Analysis

La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français

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