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Meta-Analysis
. 2005 Apr 18;2005(2):CD002859.
doi: 10.1002/14651858.CD002859.pub2.

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

M Empson  1 , M Lassere, J Craig, J Scott
Affiliations
Meta-Analysis

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

M Empson et al. Cochrane Database Syst Rev. .

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.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 1 Aspirin versus placebo or usual care.
1.2
1.2. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 2 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG.
1.3
1.3. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 3 High‐dose heparin and aspirin versus low‐dose heparin and aspirin.
1.4
1.4. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 4 Prednisone and aspirin versus aspirin or placebo.
1.5
1.5. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 5 Prednisone and aspirin versus heparin and aspirin.
1.6
1.6. Analysis
Comparison 1 All interventions ‐ pregnancy loss, Outcome 6 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin.
2.1
2.1. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 1 Pregnancy loss.
2.2
2.2. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 2 Premature delivery.
2.3
2.3. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
2.4
2.4. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 4 IUGR with interventions.
2.5
2.5. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 5 Adverse pregnancy outcome (pregnancy loss or IUGR).
2.6
2.6. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 6 Neonatal intensive care admission.
2.7
2.7. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 7 Caesarean section.
2.8
2.8. Analysis
Comparison 2 Aspirin versus placebo or usual care, Outcome 8 Weighted mean difference for birthweight.
3.1
3.1. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 1 Pregnancy loss.
3.2
3.2. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 2 Premature delivery.
3.3
3.3. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
3.4
3.4. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 4 IUGR with interventions.
3.5
3.5. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 5 Adverse pregnancy outcome (pregnancy loss or IUGR).
3.6
3.6. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 6 Neonatal intensive care admission.
3.7
3.7. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 7 Caesarean section.
3.8
3.8. Analysis
Comparison 3 Heparin (LMW and unfractionated) and aspirin versus aspirin or IVIG, Outcome 8 Weighted mean difference for birthweight.
4.1
4.1. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 1 Pregnancy loss.
4.2
4.2. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 2 Premature delivery.
4.3
4.3. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
4.4
4.4. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 4 IUGR with interventions.
4.5
4.5. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 5 Adverse pregnancy outcome (pregnancy loss or IUGR).
4.7
4.7. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 7 Caesarean section.
4.8
4.8. Analysis
Comparison 4 High‐dose heparin and aspirin versus low‐dose heparin and aspirin, Outcome 8 Weighted mean difference for birthweight.
5.1
5.1. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 1 Pregnancy loss.
5.2
5.2. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 2 Premature delivery.
5.3
5.3. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
5.4
5.4. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 4 IUGR with interventions.
5.5
5.5. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 5 Adverse pregnancy outcome (pregnancy loss or IUGR).
5.6
5.6. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 6 Neonatal intensive care admission.
5.7
5.7. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 7 Caesarean section.
5.8
5.8. Analysis
Comparison 5 Prednisone and aspirin versus aspirin or placebo, Outcome 8 Weighted mean difference for birthweight.
6.1
6.1. Analysis
Comparison 6 Prednisone and aspirin versus heparin and aspirin, Outcome 1 Pregnancy loss.
6.2
6.2. Analysis
Comparison 6 Prednisone and aspirin versus heparin and aspirin, Outcome 2 Premature delivery.
6.3
6.3. Analysis
Comparison 6 Prednisone and aspirin versus heparin and aspirin, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
7.1
7.1. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 1 Pregnancy loss.
7.2
7.2. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 2 Premature delivery.
7.3
7.3. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 3 Adverse pregnancy outcome (pregnancy loss or preterm labour).
7.4
7.4. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 4 IUGR with interventions.
7.5
7.5. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 5 Adverse pregnancy outcome (pregnancy loss or IUGR).
7.6
7.6. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 6 Neonatal intensive care admission.
7.7
7.7. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 7 Caesarean section.
7.8
7.8. Analysis
Comparison 7 IVIG (+/‐ heparin and aspirin) versus heparin (unfractionated or LMW) and aspirin or prednisone and aspirin, Outcome 8 Weighted mean difference for birthweight.
8.1
8.1. Analysis
Comparison 8 Prednisone and aspirin ‐ diabetes as an outcome, Outcome 1 Diabetes.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Branch 2000 {published and unpublished data}
    1. Branch DW, Peaceman AM, Druzin M, Silver RK, El‐Sayed Y, Silver RM, et al. A multicentre, placebo‐controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The pregnancy loss study group. American Journal of Obstetrics and Gynecology 2000;182(1 Pt 1):122‐7. - PubMed
Cowchock 1992 {published data only}
    1. Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low‐dose heparin treatment. American Journal of Obstetrics and Gynecology 1992;166(5):1318‐23. - PubMed
Cowchock 1997 {published data only}
    1. Cowchock S, Reece EA. Do low‐risk pregnant women with antiphospholipid antibodies need to be treated? Organizing group of the antiphospholipid antibody treatment trial. American Journal of Obstetrics and Gynecology 1997;176(5):1099‐100. - PubMed
Farquharson 2002 {published data only}
    1. Farquharson RG. Antiphospholipid syndrome in pregnancy: a controlled treatment trial. Journal of Obstetrics and Gynaecology 2001;21 Suppl 1:S22.
    1. Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstetrics & Gynecology 2002;100(3):408‐13. - PubMed
    1. Dadelszen P, Kent N. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstetrics & Gynecology 2003;101(3):618. - PubMed
Kutteh 1996a {published data only}
    1. Kutteh WH. Antiphospholipid antibody‐associated recurrent pregnancy loss: treatment with heparin and low‐dose aspirin is superior to low‐dose aspirin alone. American Journal of Obstetrics and Gynecology 1996;174(5):1584‐9. - PubMed
Kutteh 1996b {published data only}
    1. Kutteh WH, Ermel LD. A clinical trial for the treatment of antiphospholipid antibody‐associated recurrent pregnancy loss with lower dose heparin and aspirin. American Journal of Reproductive Immunology 1996;35(4):402‐7. - PubMed
Laskin 1997 {published data only}
    1. Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. New England Journal of Medicine 1997;337(3):148‐53. - PubMed
Pattison 2000 {published data only}
    1. Merrill JT. Appropriate management of antiphospholipid‐related pregnancy in women without lupus who have low titer autoantibodies. Current Rheumatology Reports 2001;3:269‐70. - PubMed
    1. Pattison NS, Chamley LW, Birdsall M, Zanderigo AM, Liddell HS, McDougall J. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. American Journal of Obstetrics and Gynecology 2000;183(4):1008‐12. - PubMed
Rai 1997 {published data only}
    1. Cohen H. Randomised trial of aspirin versus aspirin and heparin in pregnant women with the antiphospholipid syndrome. Annales de Medecine Interne 1996;147:44. - PubMed
    1. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997;314(7076):253‐7. - PMC - PubMed
    1. Rai R, Regan L. Antiphospholipid antibodies and recurrent miscarriage. Acta Obstetricia et Gynecologica Scandinavica 1997;76 Suppl(167:4):6.
    1. Rai RS, Cohen H, Regan L. Prospective randomized trial of aspirin versus aspirin + heparin in pregnant women with a history of recurrent miscarriage in association with antiphospholipid antibodies. Human Reproduction 1996;11:25.
Silver 1993 {published data only}
    1. Silver RK, MacGregor SN, Sholl JS, Hobart JM, Neerhof MG, Ragin A. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody‐positive obstetric patients. American Journal of Obstetrics and Gynecology 1993;169(6):1411‐7. - PubMed
    1. Silver RK, Sholl JS, MacGregor SN, Hobart JH, Neerhof MG, Hickman AH. Prospective evaluation of single (low‐dose aspirin) vs combined (aspirin plus prednisone) therapy in the treatment of the antiphospholipid syndrome. Proceedings of 39th Annual Meeting of the Society for Gynecologic Investigation; 1992; San Antonio, Texas, USA. 1992:125.
Triolo 2003 {published data only}
    1. Triolo G, Ferrante A, Ciccia F, Accardo‐Palumbo A, Perino A, Castelli A, et al. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis & Rheumatism 2003;48(3):728‐31. - PubMed
Tulppala 1997 {published data only}
    1. Tulppala M, Marttunen M, Soderstrom‐Anttila V, Ailus K, Palosuo T, Ylikorkala O. Low dose aspirin in the prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Human Reproduction 1997;12(1):191. - PubMed
    1. Tulppala M, Marttunen M, Soderstrom‐Anttila V, Foudila T, Ailus K, Palosuo T, et al. Low‐dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Human Reproduction 1997;12(7):1567‐72. - PubMed
Vaquero 2001 {published data only}
    1. Vaquero E, Lazzarin N, Valensise H, Menghini S, Pierro G, Cesa F, et al. Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low‐dose aspirin. American Journal of Reproductive Immunology (Copenhagen) 2001;45(3):174‐9. - PubMed

References to studies excluded from this review

Al‐Momen 1993 {published data only}
    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. - PubMed
Backos 1999 {published data only}
    1. 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. - PubMed
Balasch 1993 {published data only}
    1. 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. - PubMed
Blumenfeld 1991 {published data only}
    1. 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. - PubMed
Boda 1999 {published data only}
    1. 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. - PubMed
Branch 1992 {published data only}
    1. 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. - PubMed
Caruso 1997 {published data only}
    1. Caruso A, Carolis S, Ferrazzani S, Santis L, Carducci B, Trivellini C, et al. Antiphospholipid antibodies in pregnant patients. International Journal of Immunopathology & Pharmacology 1997;10(2 Suppl):137‐8.
Christiansen 1995 {published data only}
    1. 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. - PubMed
Corosu 1998 {published data only}
    1. Corosu R, Roma B, Cocola M, Marziali M. Antiphospholipid syndrome in obstetrics. Minerva Ginecologica 1998;50(1‐2):9‐13. - PubMed
Costa 1999 {published data only}
    1. Costa M, Rossi E. Antiphospholipid antibodies and pregnancy. Annals of the New York Academy of Sciences 1999;876:383‐6. - PubMed
Cowchock 1988 {published data only}
    1. Cowchock FS, Wapner RJ, Needleman L, Filer R. A comparison of pregnancy outcome after two treatments for antibodies to cardiolipin. Clinical and Experimental Rheumatology 1988;6(2):200.
Cowchock 1996 {published data only}
    1. Cowchock S. Prevention of fetal death in the antiphospholipid antibody syndrome. Lupus 1996;5(5):467‐72. - PubMed
De Veciana 2001 {published data only}
    1. 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.
Diejomaoh 2002 {published data only}
    1. 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. - PubMed
Erkan 2001 {published data only}
    1. Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin.[comment]. Arthritis & Rheumatism 2001;44(6):1466‐7. - PubMed
Franklin 2002 {published data only}
    1. Franklin RD, Kutteh WH. Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population. Human Reproduction 2002;17(11):2981‐5. - PubMed
Geva 1998 {published data only}
    1. 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. - PubMed
Gordon 1998 {published data only}
    1. Gordon C, Kilby MD. Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Lupus 1998;7:429‐33. - PubMed
Granger 1997 {published data only}
    1. Granger KA, Farquharson RG. Obstetric outcome in antiphospholipid syndrome. Lupus 1997;6(6):509‐13. - PubMed
Gris 1995 {published data only}
    1. Gris JC, Neveu S, Tailland ML, Courtieu C, Mares P, Schved JF. Use of a low‐molecular weight heparin (enoxaparin) or of a phenformin‐like substance (moroxydine chloride) in primary early recurrent aborters with an impaired fibrinolytic capacity. Thrombosis and Haemostasis 1995;73(3):362‐7. - PubMed
Gris 2002 {published data only}
    1. Gris JC, Balducchi JP, Quere I, Hoffet M, Mares P. Enoxaparin sodium improves pregnancy outcome in aspirin‐resistant antiphospholipid/antiprotein antibody syndromes. Thrombosis and Haemostasis 2002;87(3):536‐7. - PubMed
Hasegawa 1992 {published data only}
    1. Hasegawa I, Takakuwa K, Goto S, Yamada K, Sekizuka N, Kanazawa K, et al. Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody. Human Reproduction 1992;7(2):203‐7. - PubMed
Kaaja 1993 {published data only}
    1. Kaaja R, Julkunen H, Viinikka L, Ylikorkala O. Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin. Obstetrics & Gynecology 1993;81:327‐31. - PubMed
Kutteh 1997 {published data only}
    1. Kutteh WH, Yetman DL, Chantilis SJ, Crain J. Effect of antiphospholipid antibodies in women undergoing in‐vitro fertilization: Role of heparin and aspirin. Human Reproduction 1997;12(6):1171‐5. - PubMed
Kwak 1992 {published data only}
    1. Kwak JYH, Gilman‐Sachs A, Beaman KD, Beer AE. Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment. American Journal of Obstetrics and Gynecology 1992;166(6 I):1787‐98. - PubMed
Lima 1996 {published data only}
    1. Lima F, Khamashta MA, Buchanan NMM, Kerslake S, Hunt BJ, Hughes GRV. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clinical and Experimental Rheumatology 1996;14(2):131‐6. - PubMed
Lockshin 1989 {published data only}
    1. Lockshin MD, Druzin ML, Qamar T. Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody. American Journal of Obstetrics and Gynecology 1989;160:439‐43. - PubMed
Mankuta 1999 {published data only}
    1. Mankuta D, Spitzer KA, Seaward G, Farine D, Ryan G, Clark‐Soloninka C, et al. Prednisone does not affect the biophysical score in pregnant women. American Journal of Obstetrics and Gynecology 1999;180:S163.
Many A 1992 {published data only}
    1. 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(3‐4):216‐8. - PubMed
Martin 1997 {published data only}
    1. Martin ME, Fernandez CJ. Prophylaxis of the spontaneous interruption of pregnancy (fetal miscarriage) in the antiphospholipid syndrome. Revista Espanola de Reumatologia 1997;24(3):95‐100.
Mazzucconi 1996 {published data only}
    1. Mazzucconi MG, Dragoni F, Chistolini A, Peraino M, Paesano R, Di P, et al. Efficacy of low dose prednisone plus aspirin in preventing spontaneous abortions and/or fetal deaths due to antiphospholipid antibodies: results of a pilot study. Autoimmunity 1996;24(2):123‐5. - PubMed
McParland 1993 {published data only}
    1. McParland P. Low‐dose aspirin in pregnancy. Contemporary Reviews in Obstetrics and Gynaecology 1993;5(1):30‐8.
Mueller‐Eckhardt 199 {published data only}
    1. Mueller‐Eckhardt G, Mallmann P, Neppert J, Lattermann A, Melk A, Heine, et al. Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. Journal of Reproductive Immunology 1994;27(2):95‐109. - PubMed
Ogasawara 1998 {published data only}
    1. Ogasawara M, Sasa H, Katano K, Aoyama T, Aoki K, Suzumori K. Recurrent abortion and moderate or strong antiphospholipid antibody production. International Journal of Gynecology & Obstetrics 1998;62(2):183‐8. - PubMed
Passaleva 1993 {published data only}
    1. Passaleva A, Massai G, D'Elios MM, Livi C, Abbate R. Prevention of miscarriage in antiphospholipid syndrome. Autoimmunity 1993;14(2):121‐5. - PubMed
Perino 1997 {published data only}
    1. Perino A, Vassiliadis A, Vucetich A, Colacurci N, Menato G, Cignitti M, et al. Short‐term therapy for recurrent abortion using intravenous immunoglobulins: results of a double‐blind placebo‐controlled Italian study. Human Reproduction 1997;12(11):2388‐92. - PubMed
Quenby 1992 {published data only}
    1. Quenby S, Farquharson R, Ramsden G. The obstetric outcome of patients with positive anticardiolipin antibodies: aspirin versus no treatment. 26 British Congress of Obstetrics and Gynaecology; 1992; Manchester, UK. 1992:443. [443]
Rai 1997 b {published data only}
    1. Rai R, Regan L. Antiphospholipid antibodies, infertility and recurrent miscarriage. Current Opinion in Obstetrics and Gynecology 1997;9:279‐82. - PubMed
Rai 2000 {published data only}
    1. Rai R, Backos M, Baxter N, Chilcott I, Regan L. Recurrent miscarriage‐‐an aspirin a day?. Human Reproduction 2000;15(10):2220‐3. - PubMed
Reece 1997 {published data only}
    1. Reece EA, Garofalo J, Zheng X‐Z, Assimakopoulos E. Pregnancy outcome: influence of antiphospholipid antibody titer, prior pregnancy losses and treatment. Journal of Reproductive Medicine 1997;42(1):49‐55. - PubMed
Reznikoff‐Etievant {published data only}
    1. Reznikoff‐Etievant MF, Cayol V, Zou GM, Abuaf N, Robert A, Johanet C, et al. Habitual abortions in 678 healthy patients: investigation and prevention. Human Reproduction 1999;14(8):2106‐9. - PubMed
Ruffatti 1997 {published data only}
    1. Ruffatti A, Orsini A, Lenardo L, Nardelli GB, Patrassi GM, Truscia D, et al. A prospective study of fifty‐three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody‐related fetal loss. Clinical and Experimental Rheumatology 1997;15(5):499‐505. - PubMed
Sammaritano 2001 {published data only}
    1. Sammaritano LR. Update on the management of the pregnant patient with antiphospholipid antibody. Current Rheumatology Reports 2001;3(3):213‐21. - PubMed
Scopelitis 1994 {published data only}
    1. Scopelitis E, Wilson WA, Perez MC, Lynch A, Emlen W. Antiphospholipid antibodies in pregnancy. Annals of Internal Medicine 1994;121(7):547‐8. - PubMed
Semprini 1989 {published data only}
    1. Semprini AE, Vucetich A, Garbo S, Agostoni G, Pardi G. Effect of prednisone and heparin treatment in 14 patients with poor reproductive efficiency related to lupus anticoagulant. Fetal Therapy 1989;4(Suppl 1):73‐6. - PubMed
Shefras 1995 {published data only}
    1. Shefras J, Farquharson. Heparin therapy, bone density and pregnancy. 27th British Congress of Obstetrics and Gynaecology; 1995 July 4‐7; Dublin. 1995:93. [93]
Sher 1994 {published data only}
    1. Sher G, Feinman M, Zouves C, Kuttner G, Maassarani G, Salem R, et al. High fecundity rates following in‐vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin. Human Reproduction 1994;9(12):2278‐83. - PubMed
Sher 1998 {published data only}
    1. Sher G, Matzner W, Feinman M, Maassarani G, Zouves C, Chong P, et al. The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody‐positive women undergoing in vitro fertilization. American Journal of Reproductive Immunology (Copenhagen) 1998;40(2):74‐82. - PubMed
Spinnato 1995 {published data only}
    1. Spinnato J, Clark A, Pierangeli S, Harris N. Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy. American Journal of Obstetrics and Gynecology 1995;172:690‐4. - PubMed
Stern 2003 {published data only (unpublished sought but not used)}
    1. Stern, K, Kornman L, Norris H, Hale L, Baker HWG. Heparin / aspirin do not help antiphospholipid‐positive women with recurrent spontaneous abortion. Human Reproduction 2003;18(Suppl 1):55 xviii.
Takakuwa 1997 {published data only}
    1. Takakuwa K, Arakawa M, Honda K, Imai T, Tamura M, Kurabayashi T, et al. Immunosuppressive therapy for recurrent aborters with positive antiphospholipid antibodies and alteration of 6ketoPGF1 alpha/TXB2 ratio. Journal of Perinatal Medicine 1997;25(6):509‐11. - PubMed
Vahid 1999 {published data only}
    1. Vahid Dastjerdi M, Aleyasin A, Kashaf H, Marsoosi V, Aghahosscini A. The effect of acetyl salicylic acid and prednisolone before and during pregnancy in reducing unexplained recurrent abortions. Fertility and Sterility 1999;72:S203.
Yamamoto 1994 {published data only}
    1. Yamamoto H, Kanaya M, Mori S, Inoue Y, Kiya T, Goto T, et al. The prevalence and treatment of recurred spontaneous abortions caused by autoimmunity. Japanese Journal of Fertility and Sterility 1994;39(4):25‐30.

References to studies awaiting assessment

Carta 2005 {published data only}
    1. Carta G, Iovenitti P, Falciglia K. Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low‐dose aspirin and fish oil derivates. Clinical & Experimental Obstetrics & Gynecology 2005;32(1):49‐51. - PubMed
Dendrinos 2007 {published data only}
    1. Dendrinos S, Kalogirou I, Makrakis E, Theodoridis T, Mahmound EA, Christopoulou‐Cokkinou V, et al. Safety and effectiveness of tinzaparin sodium in the management of recurrent pregnancy loss. Clinical and Experimental Obstetrics and Gynecology 2007;34(3):143‐5. - PubMed
Dendrinos 2009 {published data only}
    1. Dendrinos S, Sakkas E, Makrakis E. Low‐molecular‐weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome. International Journal of Gynecology & Obstetrics 2009;104(3):223‐5. - PubMed
Ensom 2004 {published data only}
    1. Ensom MH, Stephenson MD. Pharmacokinetics of low molecular weight heparin and unfractionated heparin in pregnancy. Journal of the Society for Gynecologic Investigation 2004;11(6):377‐83. - PubMed
Goel 2006 {published data only}
    1. Goel N, Tuli A, Choudhry R. The role of aspirin versus aspirin and heparin in cases of recurrent abortions with raised anticardiolipin antibodies. Medical Science Monitor 2006;12(3):CR132‐6. - PubMed
Laskin 2009 {published data only}
    1. Laskin CA, Spitzer KA, Clark CA, Crowther MR, Ginsberg JS, Hawker GA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. Journal of Rheumatology 2009;36(2):279‐87. - PubMed
Mahmoud 2004 {published data only}
    1. Mahmoud F, Diejomaoh M, Omu A, Abul H, Haines D. Effect of IgG therapy on lymphocyte subpopulations in the peripheral blood of Kuwaiti women experiencing recurrent pregnancy loss. Gynecologic and Obstetric Investigation 2004;58(2):77‐83. - PubMed
Malinowski 2003 {published data only}
    1. Malinowski A, Dynski MA, Maciolek‐Blewniewska G, Glowacka E, Pawlowski T, Babula G. Treatment outcome in women suffering from recurrent miscarriages and antiphospholipid syndrome [Wyniki leczenia kobiet z nawracajacymi samoistnymi poronieniami i zespolem antyfosfolipidowym.]. Ginekologia Polska 2003;74(10):1213‐22. - PubMed
Merrill 2001 {published data only}
    1. Merrill JT. Appropriate management of antiphospholipid‐related pregnancy in women without lupus who have low titer autoantibodies. Current Rheumatology Reports 2001;3:269‐70. - PubMed
Noble 2005 {published data only}
    1. Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low‐molecular‐weight heparin versus unfractionated heparin. Fertility & Sterility 2005;83(3):684‐90. - PubMed
Rai 1996 {published data only}
    1. Rai RS, Regan L, Dave M, Cohen H. Prospective randomised trial of aspirin versus aspirin plus heparin in pregnant women with the antiphospholipid syndrome [abstract]. British Journal of Haematology 1996;93(Suppl 1):5.
Regan 2006 {published data only}
    1. Regan L. Steroids and antiphospholipid syndrome‐related pregnancy loss (planned trial). ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 21 March 2006).
Shu 2002 {published data only}
    1. Shu J, Miao P, Wang RJ. Clinical observation on effect of Chinese herbal medicine plus human chorionic gonadotropin and progesterone in treating anticardiolipin antibody‐positive early recurrent spontaneous abortion. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi//Chinese Journal of Integrated Traditional and Western Medicine 2002;22(6):414‐6. - PubMed
Stephenson 2004 {published data only}
    1. Stephenson MD, Ballem PJ, Tsang P, Purkiss S, Ensworth S, Houlihan E, et al. Treatment of antiphospholipid antibody syndrome (aps) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin. Journal of Obstetrics & Gynaecology Canada: JOGC 2004;26(8):729‐34. - PubMed
Tulppala 1997a {published data only}
    1. Tulppala M, Marttunen M, Soderstrom‐Anttila V, Ailus K, Palosuo T, Ylikorkala O. Low dose aspirin in the prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Human Reproduction 1997;12(1):191. - PubMed

Additional references

Alderson 2004
    1. Alderson P, Green S, Higgins JPT, editors. Medline search strategies for optimal sensitivity in identifying randomised clinical trials. Cochrane Reviewers’ Handbook 4.2.2 [updated December 2003]; 11a. Appendix B. In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Carreras 1988
    1. Carreras LO, Perez G, Vega H, Casavilla F. Lupus anticoagulant and recurrent fetal loss: successful treatment with gammaglobulin. Lancet 1988;ii:393‐4. - PubMed
Chamley 1998
    1. Chamley L, Duncalf A, Mitchell M, Johnson P. Action of anticardiolipin and antibodies to beta2‐glycoprotein‐1 on trophoblast proliferation as a mechanism for fetal death. Lancet 1998;352:1037‐8. - PubMed
Chamley 2002
    1. Chamley L. Antiphospholipid antibodies: biological basis and prospects for treatment. Journal of Reproductive Immunology 2002;57(1‐2):185‐202. - PubMed
Di Simone 1997
    1. Simone N, Ferrazzani S, Castellani R, Carolis S, Mancuso S, Caruso A. Heparin and low‐dose aspirin restore placental human chorionic gonadotrophin secretion abolished by antiphospholipid antibody‐containing sera. Human Reproduction 1997;12(9):2061‐5. - PubMed
Di Simone 1999
    1. Simone N, Caliandro D, Castellani R, Ferrazzani S, Carolis S, Caruso A. Low‐molecular weight heparin restores in‐vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome. Human Reproduction 1999;14(2):489‐95. - PubMed
Duley 2007
    1. Duley L, Henderson‐Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre‐eclampsia and its complications. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD004659.pub2] - DOI - PubMed
Elder 1988
    1. Elder M, Swiet M, Robertson A, Flloyd E, Hawkins D. Low‐dose aspirin in pregnancy. Lancet 1988;i:410. - PubMed
Ensom 1999
    1. Ensom MH, Stephenson MD. Low‐molecular‐weight heparins in pregnancy. Pharmacotherapy 1999;19(9):1013‐25. - PubMed
Forastiero 1997
    1. Forastiero RR, Martinuzzo ME, Cerrato GS, Kordich LC, Carreras LO. Relationship of anti beta2‐glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies. Thrombosis and Haemostasis 1997;78(3):1008‐14. - PubMed
Francois 1988
    1. Francois A, Freund M, Daffos F, Remy P, Aiach M, Jacquot C. Repeated fetal losses and lupus anticoagulant. Annals of Internal Medicine 1988; Vol. 109:993‐4. - PubMed
Glasziou 1995
    1. Gasziou P, Irwig L. An evidence based approach to indivdualising treatment. BMJ 1995;311:1356‐9. - PMC - PubMed
Higashino 1998
    1. 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. - PubMed
Hirsh 1998
    1. 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. - PubMed
Kobayashi 1992
    1. 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. - PMC - PubMed
Laurell 1957
    1. Laurell A, Nilsson I. Hypergammaglobulinaemia, circulating anticoagulant, and biologic false positive Wassermann Reaction. Journal of Laboratory and Clinical Medicine 1957;49(5):694‐707. - PubMed
Lockwood 1989
    1. 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. - PubMed
Lubbe 1983
    1. Lubbe W, Butler W, Palmer S, Liggins G. Fetal survival after prednisone suppression of maternal lupus‐anticoagulant. Lancet 1983;i:1361‐3. - PubMed
Lubbe 1985
    1. Lubbe W, Liggins G. Lupus anticoagulant and pregnancy. American Journal of Obstetrics and Gynecology 1985;153:322‐7. - PubMed
Lynch 1994
    1. 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. - PubMed
Lynch 1999
    1. 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. - PubMed
Many 1992
    1. 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. - PubMed
Nelson‐Piercy 1994
    1. Nelson‐Piercy C. Low molecular weight heparin for obstetric thromboprophylaxis. British Journal of Obstetrics and Gynaecology 1994;101:9‐17. - PubMed
Nilsson 1975
    1. Nilsson I, Astedt B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant ("antithromboplastin"). Acta Medicine Scandinavia 1975;197:153‐9. - PubMed
Rai 1995
    1. 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. - PubMed
Rand 1994
    1. 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. - PubMed
Rand 1997
    1. 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. - PubMed
Rosove 1990
    1. 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. - PubMed
Salafia 1997
    1. Salafia CM, Cowchock FS. Placental pathology and antiphospholipid antibodies: a descriptive study. American Journal of Perinatology 1997;14(8):435‐41. - PubMed
Sandercock 2004
    1. 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.
Schulz 1995
    1. 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. - PubMed
Scott 1988
    1. Scott J, Branch D, Kochenour N, Ward K. Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization. American Journal of Obstetrics and Gynaecology 1988;159:1055‐6. - PubMed
Shefras 1996
    1. Shefras J, Farquharson R. Bone density studies in pregnant women receiving heparin. European Journal of Obstetrics & Gynecology and Reproductive Biology 1996;65:171‐4. - PubMed
Wilson 1999
    1. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.[see comment]. Arthritis & Rheumatism 1999;42(7):1309‐11. - PubMed
Yasuda 1995
    1. Yasuda M, Takakuwa K, Tokunaga A, Tanaka K. Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstetrics & Gynecology 1995;86(4 Pt 1):555‐9. - PubMed
Yetman 1996
    1. Yetman DL, Kutteh WH. Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies. Fertility and Sterility 1996;66(4):540‐6. - PubMed

References to other published versions of this review

Empson 2002
    1. Empson M, Lassere M, Craig J, Scott J. Recurrent pregnancy loss with antiphospholipid antibody: A systematic review of therapeutic trials. Obstetrics & Gynecology 2002;99(1):135‐44. - PubMed

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