CoChat
Sign Up
Cited by 486Systemic Lupus Erythematosus ResearchReproductive System and PregnancyBlood Coagulation and Thrombosis Mechanisms

Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant

Open access
Empson, Marianne B, Lassere, Marissa, Craig, Jonathan C, Scott, James R·2005·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd002859.pub2PMC PMC6768987
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks. OBJECTIVES: To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL. SEARCH STRATEGY: We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999. SELECTION CRITERIA: Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999. MAIN RESULTS: Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials. Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes. AUTHORS' CONCLUSIONS: Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/14651858.cd002859.pub2

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A high quality meta-analysis of RCTs showed that the only treatment or treatment combination that led to a significant increase in the live birth rate in women with recurrent miscarriage and APS was aspirin with unfractionated heparin (UFH) infusion.

    “A high quality meta-analysis of RCTs assessed pregnancy outcomes for women with recurrent miscarriage and APS who were treated with aspirin, steroids, intravenous globulin and heparin.It showed that the only treatment or treatment combination that lead to a significant increase in the live birth rate was aspirin with unfractionated heparin (UFH) infusion.163”

    From Recurrent MiscarriageGreen‐top Guideline No. 17 (2023) · cites this paper as [163]

    The Main results and Heparin sections report that, among the interventions examined, only unfractionated heparin combined with aspirin significantly reduced pregnancy loss compared with aspirin alone, supporting the live-birth finding. However, the paper does not describe UFH as an infusion, and its Main results say the quality of the included trials was not high. Page numbers are unavailable in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Aspirin plus unfractionated heparin significantly reduced the miscarriage rate by 54% compared with aspirin alone (RR 0.46, 95% CI 0.29-0.71).

    “This treatment combination significantly reduced the miscarriage rate by 54% (aspirin plus UFH versus aspirin alone RR 0.46, 95% CI 0.29-0.71).”

    From Recurrent MiscarriageGreen‐top Guideline No. 17 (2023) · cites this paper as [163]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 38

  1. Al-Momen AKM, Moghraby SA, El-Rab MOG, Gader AMA, al- Balla SR, Al, Meshari AA, al-Nuaim L. Pregnancy outcome in women with antiphospholipid antibodies. Clinical Rheumatology 1993;12(3):381-6.
  2. Backos 1999 {published data only} Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. British Journal of Obstetrics and Gynaecology 1999;106(2):102-7.
  3. Balasch 1993 {published data only} Balasch J, Carmona F, Lopez-Soto A, Font J, Creus M, Fabregues F, et al. Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome. Human Reproduction 1993;8(12):2234-9.
  4. Blumenfeld 1991 {published data only} Blumenfeld Z, Weiner Z, Lorber M, Sujov P, Thaler I. Anticardiolipin antibodies in patients with recurrent pregnancy wastage: treatment and uterine blood flow. Obstetrics & Gynecology 1991;78(4):584-9.
  5. Boda Z, Laszlo P, Pfliegler G, Tornai I, Rejto L, Schlammadinger A. Low molecular weight heparin as thromboprophylaxis throughout pregnancy in heritable thrombophilic women. Clinical and applied thrombosis/ hemostasis 1999;5(3):198-9.
  6. Branch 1992 {published data only} Branch DW, Silver RM, Blackwell JL, Reading JC, Scott JR. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstetrics & Gynecology 1992;80(4):614-20.
  7. Caruso A, De Carolis S, Ferrazzani S, De Santis L, Carducci B, Trivellini C, et al. Antiphospholipid antibodies in pregnant patients. International Journal of Immunopathology & Pharmacology 1997;10(2 Suppl):137-8.
  8. Christiansen 1995 {published data only} Christiansen OB, Mathiesen O, Husth M, Rasmussen KL, Ingerslev HJ, Lauritsen JG, et al. Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin. Human Reproduction 1995;10(10):2690-5.
  9. Corosu 1998 {published data only} Corosu R, Roma B, Cocola M, Marziali M. Antiphospholipid syndrome in obstetrics. Minerva Ginecologica 1998;50(1-2):9-13.
  10. Costa 1999 {published data only} Costa M, Rossi E. Antiphospholipid antibodies and pregnancy. Annals of the New York Academy of Sciences 1999;876:383-6.
  11. Cowchock 1988 {published data only} Cowchock FS, Wapner RJ, Needleman L, Filer R. A comparison of pregnancy outcome a er two treatments for antibodies to cardiolipin. Clinical and Experimental Rheumatology 1988;6(2):200.
  12. Cowchock 1996 {published data only} Cowchock S. Prevention of fetal death in the antiphospholipid antibody syndrome. Lupus 1996;5(5):467-72.
  13. De Veciana 2001 {published data only} De Veciana M TP, Dattel B, Slotnick R, Abuhamad A. Dalteparin versus unfractionated heparin for prophylactic anticoagulation during pregnancy (abstract). American Journal of Obstetrics and Gynecology 2001;185(6 Suppl):S182.
  14. Diejomaoh 2002 {published data only} Diejomaoh MF, Al-Azemi MM, Bandar A, Egbase PE, Jirous J, Al-Othman S, et al. A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome. Archives of Gynecology and Obstetrics 2002;266(2):61-6.
  15. Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD. High thrombosis rate a er fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. [comment]. Arthritis & Rheumatism 2001;44(6):1466-7.
  16. Franklin 2002 {published data only} Franklin RD, Kutteh WH. Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population. Human Reproduction 2002;17(11):2981-5.
  17. Geva 1998 {published data only} Geva E, Amit A, Lerner-Geva L, Lessing J.B. Prevention of early pregnancy loss in autoantibody seropositive women (letter). Lancet 1998;351(9095):34-5.
  18. Gordon 1998 {published data only} Gordon C, Kilby MD. Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Lupus 1998;7:429-33.
  19. Granger 1997 {published data only} Granger KA, Farquharson RG. Obstetric outcome in antiphospholipid syndrome. Lupus 1997;6(6):509-13.
  20. Gasziou P, Irwig L. An evidence based approach to indivdualising treatment. BMJ 1995;311:1356-9.
  21. Higashino M, Takakuwa K, Arakawa M, Tamura M, Yasuda M, Tanaka K. Anti-cardiolipin antibody and anti-cardiolipin beta-2-glycoprotein I antibody in patients with recurrent fetal miscarriage. Journal of Perinatal Medicine 1998;26(5):384-9.
  22. Hirsh J, Warkentin T, Raschke R, Granger C, Ohman E, Dalen J. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998;114(5):489S-510.
  23. Kobayashi S, Tamura N, Tsuda H, Mokuno C, Hashimoto H, Hirose S. Immunoadsorbent plasmapheresis for a patient with antiphospholipid syndrome during pregnancy. Annals of the Rheumatic Diseases 1992;51(3):399-401.
  24. Laurell A, Nilsson I. Hypergammaglobulinaemia, circulating anticoagulant, and biologic false positive Wassermann Reaction. Journal of Laboratory and Clinical Medicine 1957;49(5):694-707.
  25. Lockwood C, Romero R, Feinberg R, Clyne L, Coster B, Hobbins J. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. American Journal of Obstetrics and Gynecology 1989;161:369-73.
  26. Lubbe W, Liggins G. Lupus anticoagulant and pregnancy. American Journal of Obstetrics and Gynecology 1985;153:322-7.
  27. Lynch A, Marlar R, Murphy J, Davila G, Santos M, Rutledge J, et al. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Annals of Internal Medicine 1994;120(6):470-5.
  28. Lynch A, Byers T, Emlen W, Rynes D, Shetterly SM, Hamman RF. Association of antibodies to beta2-glycoprotein 1 with pregnancy loss and pregnancy-induced hypertension: a prospective study in low-risk pregnancy. Obstetrics & Gynecology 1999;93(2):193-8.
  29. Many A, Pauzner R, Carp H, Langevitz P, Martinowitz U. Treatment of patients with antiphospholipid antibodies during pregnancy. American Journal of Reproductive Immunology 1992;28:216-8.
  30. Nelson-Piercy C. Low molecular weight heparin for obstetric thromboprophylaxis. British Journal of Obstetrics and Gynaecology 1994;101:9-17.
  31. Nilsson I, Astedt B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant ("antithromboplastin"). Acta Medicine Scandinavia 1975;197:153-9.
  32. Rai RS, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Human Reproduction 1995;10(12):3301-4.
  33. Rand JH, Wu XX, Guller S, Gil J, Guha A, Scher J, et al. Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion. American Journal of Obstetrics and Gynecology 1994;171(6):1566-72.
  34. Rand JH, Wu XX, Andree H, Lockwood C, Guller S, Scher J, et al. Pregnancy loss in the antiphospholipid-antibody syndrome - a possible thrombogenic mechanism. New England Journal of Medicine 1997;337:154-60.
  35. Rosove M, Tabsh B, Wasserstrum N, Howard P, Hahn B, Kalunian K. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstetrics & Gynecology 1990;75(4):630-4.
  36. Salafia CM, Cowchock FS. Placental pathology and antiphospholipid antibodies: a descriptive study. American Journal of Perinatology 1997;14(8):435-41.
  37. Sandercock P, Algra A, Anderson C, Bath P, Bereczki D, Berge E, et al. Stroke Group. About the Cochrane Collaboration (Collaborative Review Groups (CRGs)) 2004, Issue 4. Art. No.: STROKE.
  38. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12.

Cited by

Sorted by citations

Authors
Empson, M. B., Lassere, M., Craig, J. C., & Scott, J. R.
Affiliations
  • Meditrina Ltd; Suite 314, 453a Mt Eden Road Mt Eden Auckland New Zealand 1024
  • St George Hospital (AU)
  • The University of Sydney (AU)
  • University of Utah (US)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2005-04-20
Volume
2012
Issue
2
Pages
CD002859-CD002859
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd002859.pub2
PMC
PMC6768987
OpenAlex
W1548346841
Cited by
486
References
2
Citations by year
2026: 6 · 2025: 6 · 2024: 14 · 2023: 11 · 2022: 10 · 2021: 16 · 2020: 12 · 2019: 17 · 2018: 22 · 2017: 33 · 2016: 23 · 2015: 39 · 2014: 32 · 2013: 37 · 2012: 32
FWCI
3.63
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
recurrent pregnancy loss, antiphospholipid antibodies, lupus anticoagulant, pregnancy loss prevention, heparin, aspirin, low molecular weight heparin, prednisone, anticoagulation, preterm birth, pregnancy outcomes, thrombosis risk, antiphospholipid syndrome, treatment efficacy and safety
MeSH terms
Abortion, Habitual, Aspirin, Drug Therapy, Combination, Female, Fibrinolytic Agents, Heparin, Heparin, Low-Molecular-Weight, Humans, Prednisone, Pregnancy, Lupus Coagulation Inhibitor, Antibodies, Antiphospholipid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review