Prevention of Recurrent Miscarriage for Women with Antiphospholipid Antibody or Lupus Anticoagulant

Comment: The quality of evidence is downgraded by study quality.

A meta-analysis cd012852 included 19 RCTs with 1251 pregnant women recurrent spontaneous abortion and antiphospholipid antibody syndrome. Compared to placebo, live birth rate was improved in aspirin plus heparin group (RR1.23, 95% CI 1.12 to 1.36; p < .0001) or heparin alone group (RR 1.18, 95% CI 1.03 to 1.35; p = .02);, but not ina aspirin alone group (RR0.97, 95% CI 0.8 to 1.16; p = .71). Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding.

A meta-analysis included 5 RCT 3 analyzing the effect of heparin (unfractionated heparin or low molecular weight heparin LMWH) plus aspirin compared with aspirin alone on the live-birth rate in women with a history of at least two miscarriages and antiphospholipid antibodies.The pooled effect of unfractionated heparin and low molecular weight heparin was evaluable in three and two randomized controlled studies, respectively, with regard to live births, which was the major outcome. Overall, treatment effects were in favor of heparin against first-trimester losses (OR 0.39, 95% CI 0.24 to 0.65, number needed to treat (NNT) 6). More specifically, unfractionated heparin displayed a significant effect (OR 0.26, 95% CI 0.14-0.48; 3 trials, NNT 4), while the pooled effect of LMWH was insignificant (OR 0.70, 95% CI 0.34 to 1.45; 2 trials). Combination therapy of either unfractionated heparin or LMWH with aspirin failed to display any significant effect in the prevention of late-pregnancy losses.

A prospective, multicenter RCT 2compared low-molecular-weight (LMW) heparin plus low-dose aspirin with intravenous immunoglobulin (IVIG) in the treatment of antiphospholipid antibody syndrome in women with recurrent spontaneous abortions before 10 weeks of gestation (85 patients aged 18-39 years). The women treated with LMW heparin plus low-dose aspirin had a higher rate of live births (29/40, 72.5%) than those treated with IVIG (15/38, 39.5%); OR 1.80; 95% CI 1.14 to 2.84; P=0.007).

A Cochrane review [Abstract] 1 included 11 studies with a total of 1672 women with antiphospholipid antibodies and recurrent pregnancy loss. Heparin (either low-molecular-weight heparin or unfractionated heparin) plus aspirin increased the number of live births (RR 1.27, 95% CI 1.09 to 1.49; 5 studies, n=1295).

References

• Hamulyák EN, Scheres LJ, Marijnen MC et al. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev 2020;(5):CD012852. [PubMed]
• Dendrinos S, Sakkas E, Makrakis E. Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome. Int J Gynaecol Obstet 2009;104(3):223-5. [PubMed]
• Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol 2010;115(6):1256-62. [PubMed]
• Lu C, Liu Y, Jiang HL. Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2019;32(8):1299-1311. [PubMed]