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Evidence summaries

Antithrombotic Therapy for Women Considered at Risk of Placental Dysfunction

Heparin therapymight possibly be effective for decreasing recurrent placenta-mediated pregnancy complications like fetal growth restriction or preterm birth compared with no treatment in women at risk of placental dysfunction. Level of evidence: "D"

A Cochrane review [Abstract] 1 included 10 studies with a total of 1039 subjects. 9 studies compared heparin (alone or in combination with dipyridamole or low-dose aspirin) with no treatment; and one compared trapidil (triazolopyrimidine). Heparin was associated with a reduction in the risk of perinatal mortality (RR 0.40; 95% confidence intervals (CI) 0.20 to 0.78; 6 trials, n=653), preterm birth before 34 (RR 0.46; 95% CI 0.29 to 0.73; 3 trials, n=494) and 37 (RR 0.72; 95% CI 0.58 to 0.90; 5 trials, n=621) weeks' gestation, and infant birthweight less than the 10th centile for gestational age (RR 0.41; 95% CI 0.27 to 0.61; 7 trials, n=710). There is a lack of reliable information of clinically relevant, serious adverse infant health outcomes.

A meta-analysis 2 included 8 RCTs of low-molecular-weight heparin to prevent recurrent pregnancy complications. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (88%) with a mean age of 30.9 years (SD 5·0) and 42% had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (LMWH 62/444 [14%] versus no-LMWH 95/443 (22%) absolute difference -8%, 95% CI -17.3 to 1.4, p=0.09; relative risk 0.64, 95% CI 0.36 to 1.11, p=0.11). There was a significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, LMWH in multicentre trials reduced the primary outcome in women with previous abruption (p=0.006) but not in any of the other subgroups of previous complications.

Another meta-analysis 3 inclulded 5 studies with a total of 403 patients; 68 developed pre-eclampsia and 118 fetal growth restriction (FGR). The overall use of LMWHs was associated with a risk reduction for pre-eclampsia (RR 0.37; 95 % CI 0.22 to 0.61) and FGR (RR 0.41; 95 % CI 0.19 to 0.93) vs. no treatment.

Comment: The quality of evidence is downgraded by study quality, heterogeneity, and imprecise results).

    References

    • Dodd JM, McLeod A, Windrim RC et al. Antithrombotic therapy for improving maternal or infant health outcomes in women considered at risk of placental dysfunction. Cochrane Database Syst Rev 2013;(7):CD006780. [PubMed]
    • Rodger MA, Gris JC, de Vries JIP et al. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet 2016;388(10060):2629-2641.[PubMed]
    • Mastrolia SA, Novack L, Thachil J et al. LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis. Thromb Haemost 2016;116(5):868-878.[PubMed]

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