BACKGROUND AND PURPOSE:

• Due to conflicting evidence, Cruz-Lemini et al. (AJOG, 2021) studied the effectiveness of LMWH for the prevention of preeclampsia and other placenta-related complications in high-risk women

METHODS:

• Systematic review and meta-analysis
• Data sources
  • PubMed | Cochrane Central Register of Controlled Trials | Abstracts of congresses and scientific meetings | Reference lists of retrieved articles | Published study protocols
  • No publication time restrictions
• Study inclusion criteria
  • RCTs
  • Studies that compared LMWH or unfractionated heparin (with or without low-dose aspirin) with either placebo or low-dose aspirin (LDA) alone
  • Population: High-risk women, defined as either
    • History of preeclampsia, intrauterine growth restriction, fetal demise, or miscarriage or
    • Screen positive for preeclampsia in the first trimester
• Study design
  • In addition to overall meta-analysis, subgroup analyses were performed to assess the following
    • Combination LDA and LMWH | LMWH type | Gestational age when treatment was started | Study population particulars (e.g., presence of thrombophilia)
  • Odds ratios (OR) were calculated using a random-effects model
  • Quality of evidence was assessed using GRADE criteria
• Primary outcome
  • Development of preeclampsia
• Secondary outcomes
  • Small for gestational age
  • Perinatal death
  • Miscarriage
  • Placental abruption
  • Preterm birth

RESULTS:

• 15 studies | 2795 participants
• In high-risk women, treatment with LMWH was associated with reduced odds of
  • Preeclampsia: OR 0.62 (95% CI, 0.43 to 0.90; P=0.010)
  • Small for gestational age: OR 0.61 (95% CI, 0.44 to 0.85; P=0.003)
  • Perinatal death: OR 0.49 (95% CI, 0.25 to 0.94; P=0.030)
• This reduction in preeclampsia was stronger if LMWH was started <16 weeks
  • OR 0.55 (95% CI, 0.39 to 0.76; P=0.0004)
• In analyses that included only combined LMWH and LDA, there was a significant reduction in preeclampsia with the combined treatment vs LDA alone
  • OR 0.62 (95% CI, 0.41 to 0.95; P=0.030)
• Adverse events
  • There was no difference in adverse events between the groups overall, nor when LMWH was combined with LDA
• Quality of evidence ranged from very low to moderate due to a lack of blinding, imprecision, and inconsistency
• Type of LMWH
  • Enoxaparin and dalteparin were both associated with a significant reduction in preeclampsia
  • No statistical differences were seen between these medications
• Secondary outcomes
  • LMWH was associated with reduced risk for SGA
  • LMWH was not associated with reduced risk for other secondary outcomes

CONCLUSION:

• For high-risk women, LMWH was associated with a reduced risk of preeclampsia and other placental complications
  • Risk reduction was stronger if treatment started <16 weeks
• A combination of LMWH and low-dose aspirin was associated with a reduced risk of preeclampsia compared to LDA alone
• The authors suggest 2 potential strategies based on these findings

(1) in a priori low-risk population screened for PE by first-trimester algorithms, prophylaxis with 150 mg of aspirin daily from 12 weeks’ gestation onward

(2) high-risk women based on adverse obstetrical history of placental complications (early-onset PE, SGA, or fetal demise) could benefit from a combined prophylaxis strategy with LMWH plus LDA begun before 16 weeks’ gestation, regardless of the presence of thrombophilia

Learn More – Primary Sources:

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

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