Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized and quasi-randomized controlled trials
PubMed 24995856 · doi:10.1002/14651858.CD004734.pub4
What was done
Authors conducted a Cochrane systematic review searching trials through October 2013 for randomized and quasi-randomized controlled trials assessing aspirin, unfractionated heparin, or low molecular weight heparin (LMWH) in women with at least two unexplained miscarriages, with or without inherited thrombophilia. Treatments were compared against each other, placebo, or no treatment for live birth rates, obstetric complications, and adverse events.
What was found
Nine studies with 1,228 women were included. Three studies had a high risk of bias. In sensitivity analyses excluding high-risk studies, anticoagulants provided no live birth benefit: - Aspirin vs. placebo: RR 0.94 (95% CI 0.80 to 1.11, n = 256) - LMWH vs. aspirin: RR 1.08 (95% CI 0.93 to 1.26, n = 239) - LMWH plus aspirin vs. no treatment: RR 1.01 (95% CI 0.87 to 1.16, n = 322) Preterm delivery, pre-eclampsia, intrauterine growth restriction, and congenital malformations showed no significant differences. Aspirin did not increase bleeding risk, but combined LMWH plus aspirin significantly increased bleeding in one study, and nearly 40% of patients reported local injection-site reactions with LMWH.
Why it matters
Anticoagulant therapy does not improve live birth rates in unexplained recurrent miscarriage and adds risks of bleeding and injection-site reactions, arguing against its routine clinical use.
Limits
Three of the nine studies were at high risk of bias, and only one low-risk study was placebo-controlled. Interventions and dosages were heterogeneous, sample sizes for individual comparisons were modest, and data were insufficient to draw separate conclusions for women with inherited thrombophilia.
Cited by
- contradicts Universal prophylactic use of enoxaparin in women following a first or second miscarriage would result in 2,000 to 15,000 additional live births per year in the United States.