Recurrent pregnancy loss with antiphospholipid antibody: a systematic review of therapeutic trials

Obstet Gynecol. 2002 Jan;99(1):135-44. doi: 10.1016/s0029-7844(01)01646-5.


Objective: To explore the effects of interventions given to improve pregnancy outcome in women with antiphospholipid antibodies.

Data sources: Cochrane Controlled Trials Register, Cochrane Collaboration Pregnancy and Childbirth Group's Specialized Register of Controlled Trials, EMBASE, and MEDLINE were searched in December 1999.

Study selection: Randomized or quasi-randomized controlled trials of therapy for pregnancy loss associated with antiphospholipid antibodies were identified.

Tabulation, integration, and results: Trial selection, data extraction, and quality assessment were performed by two authors independently. Quantitative analysis of summary data was performed using the fixed- and random-effects models with heterogeneity assessments. Pregnancy loss and adverse neonatal outcomes were the main outcome measures. Ten trials (n = 627) fulfilled the inclusion criteria (of which four lacked adequate allocation concealment). Three trials of aspirin alone showed no significant reduction in pregnancy loss (relative risk [RR] 1.05, 95% confidence interval [CI] 0.66, 1.68). Heparin combined with aspirin (two trials, 140 patients) significantly reduced pregnancy loss compared with aspirin alone (RR 0.46, 95% CI 0.29, 0.71). Prednisone and aspirin resulted in a significant increase in prematurity (RR 4.83, 95% CI 2.85, 8.21) but no significant reduction in pregnancy loss (RR 0.85, 95% CI 0.53, 1.36).

Conclusion: Combination therapy with aspirin and heparin may reduce pregnancy loss in women with antiphospholipid antibodies by 54%. Further large, randomized controlled trials with adequate allocation concealment are necessary to exclude significant adverse effects.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / epidemiology
  • Abortion, Habitual / etiology
  • Adult
  • Antibodies, Antiphospholipid / analysis
  • Antibodies, Antiphospholipid / drug effects*
  • Antibodies, Antiphospholipid / immunology
  • Antiphospholipid Syndrome / complications*
  • Antiphospholipid Syndrome / drug therapy*
  • Antiphospholipid Syndrome / immunology
  • Aspirin / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Heparin / administration & dosage*
  • Humans
  • Incidence
  • Prednisone / administration & dosage*
  • Pregnancy
  • Pregnancy Outcome*
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome


  • Antibodies, Antiphospholipid
  • Heparin
  • Aspirin
  • Prednisone