Early Prophylactic Enoxaparin for the Prevention of Preeclampsia and Intrauterine Growth Restriction: A Randomized Trial

Llurba, Elisa; Bella, Miriam; Burgos, Jorge; Mazarico, Edurne; Gómez-Roig, María Dolores; Diego, Raül De; Martínez-Astorquiza, Txantón; Alijotas‐Reig, Jaume; Sánchez‐Durán, María Ángeles; Sánchez, Olga; Carreras, Elena; Cabero, L.

doi:10.1159/000509662

Cited by 16 publications

(21 citation statements)

References 35 publications

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“…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%

“…With the exception of bleeding and allergies, other adverse effects reported were very rare. Thrombocytopenia was reported in 3 studies, 22,38,42 with a range between 0 and 6 events; thrombosis was reported in 3 studies, 22,38,39 with a range between 0 and 4 events, and finally, another study reported similar numbers of transfusion events in both groups. 42 Uni-vs multicenter studies.…”

Section: Systematic Review Ajogorgmentioning

confidence: 98%

“…21 Moreover, 2 recent randomized trials in high-risk patients showed that the addition of enoxaparin to standard care did not reduce the risk of recurrence of PE and FGR. 22,23 However, the effect of heparin in preventing such conditions is likely to be higher than previously observed, if specific groups of high-risk women are selected or if heparin is combined with LDA. 22,24…”

Section: Introductionmentioning

confidence: 97%

“…22,23 However, the effect of heparin in preventing such conditions is likely to be higher than previously observed, if specific groups of high-risk women are selected or if heparin is combined with LDA. 22,24…”

Section: Introductionmentioning

confidence: 97%

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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: Systematic Review Ajogorgmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

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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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“…The benefits of this standard regime may be largely attributable to LDA since it has been shown to improve gestational complications when used alone in women at risk of pre-eclampsia without ARD, with a reduction in preeclampsia in 53% of cases, IUGR in 56% and preterm birth in 78% of cases (37). Furthermore, a recent randomized trial by Llurba et al (38) found that LMWH in women at high risk of pre-eclampsia without thrombophilia did not reduce placental insufficiency compared with no intervention.…”

Section: Discussionmentioning

confidence: 99%

Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review

Muñoz

Ahmed

Thomas

et al. 2021

Lupus

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Background Not all patients fulfil criteria for specific autoimmune rheumatic diseases (ARDs) and are then defined as having non-criteria (nc)ARD. It is uncertain whether well-recognised associations with adverse pregnancy outcomes in patients with criteria ARD also exist in patients with ncARD or undifferentiated connective tissue disease (UCTD). Therefore, we undertook a systematic review of the prevalence of adverse pregnancy outcomes in various ncARD and UCTD compared with criteria ARD to identify whether there are increased risks and to examine for any benefits of treatment. Methods This study was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using online databases including Medline and PubMed from inception to the beginning of April 2021 using appropriate keywords for various ARD and pregnancy outcomes. Results After screening 665 articles, 36 articles were chosen for full text review and 15 selected for final analysis. There were eight studies of nc antiphospholipid syndrome (APS) of more than 7000 pregnancies and seven studies of UCTD of more than 1000 pregnancies. No studies of any other ncARD in pregnancy were identified. We found that patients with either ncAPS or UCTD seem to have an increased burden of poor pregnancy outcomes compared with the general population. Despite the heterogeneity and poor quality of the studies, we also noted that ncAPS and criteria APS patients may have similar rates of obstetric complications with standard and/or non-standard APS treatment regimens. Conclusion Our findings of increased risks of poor pregnancy outcomes in patients with ncAPS or UCTD will be helpful for pre-pregnancy counselling and management of these patients in pregnancy and support their referral to specialist obstetric-rheumatology and obstetric-haematology clinics.

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Effect of low‐molecular‐weight heparin on placenta‐mediated fetal growth restriction in a tertiary referral hospital: A 7‐year retrospective cohort study

Xu,

Tang,

Peng

et al. 2023

Intl J Gynecology & Obste

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ObjectiveTo investigate the effect of low‐molecular‐weight heparin (LMWH) on placenta‐mediated fetal growth restriction (FGR).MethodsA cohort of 570 pregnant women diagnosed with placenta‐mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1‐week prescription from diagnosis of placenta‐mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self‐administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes.ResultsAfter controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35–4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14–5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48–3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early‐onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late‐onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non‐severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001).ConclusionUse of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta‐mediated FGR, particularly reducing the risk of intrauterine fetal death.

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Early Prophylactic Enoxaparin for the Prevention of Preeclampsia and Intrauterine Growth Restriction: A Randomized Trial

Cited by 16 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

Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review

Effect of low‐molecular‐weight heparin on placenta‐mediated fetal growth restriction in a tertiary referral hospital: A 7‐year retrospective cohort study

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