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Semin Reprod Med 2000; 18(4): 379-392
DOI: 10.1055/s-2000-13728
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Autoimmunity and Pregnancy Loss

M. Bardett Fausett, D. Ware Branch
  • Department of Obstetrics & Gynecology, University of Utah School of Medicine, Salt Lake City, Utah
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Publication History

Publication Date:
31 December 2000 (online)

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ABSTRACT

Clinicians have recognized for several decades that certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. During the 1980s, investigations focused attention on fetal wastage in women with antiphospholipid antibodies and the antiphospholipid antibody syndrome (APS) was characterized. Its defining features include fetal wastage in the presence of significant levels of anticardiolipin antibodies. Since that time, interest in other autoimmune diatheses and various specific autoantibodies as possible causes of pregnancy loss has increased. Investigators have attempted to establish an association between recurrent pregnancy loss and the presence of a specific autoantibody or patterns of autoantibodies. Thus far, only modest evidence supports the concept that other autoantibodies are linked to, much less cause, pregnancy loss. In this review, we will define pregnancy loss in its various forms and discuss pregnancy loss in well-characterized autoimmune diseases such as SLE and APS. We will focus on the diagnosis and management of these conditions in women attempting to achieve successful pregnancies. Later we discuss the evidence concerning the less well defined association of antiphospholipid antibodies other than the lupus anticoagulant and anticardiolipin antibodies to recurrent pregnancy loss. We then outline the significance of antinuclear antibodies and antithyroid antibodies pertaining to adverse pregnancy outcome and conclude by summarizing and making some suggestions for further study.

KEYWORD

Pregnancy loss - fetal death - recurrent miscarriage - systemic lupus erythematosus - antiphospholipid antibody syndrome - autoimmune diseases - autoantibodies

REFERENCES

  • 1 Harris E N. Syndrome of the black swan.  Br J Rheumatol . 1987;  26 324-326
    CrossrefPubMedSearch in Google Scholar
  • 2 Hughes G R, Harris N N, Gharavi A E. The anticardiolipin syndrome.  J Rheumatol . 1986;  13 486-489
    PubMedSearch in Google Scholar
  • 3 Coulam C B, Branch D W, Clark D A. American Society for Reproductive Immunology report of the Committee for Establishing Criteria for Diagnosis of Reproductive Autoimmune Syndrome.  Am J Reprod Immunol . 1999;  41 121-132
    PubMedSearch in Google Scholar
  • 4 Fraga A, Mintz G, Orozco J, Orozco J. Sterility and fertility rates, fetal wastage and maternal morbidity in systemic lupus erythematosus.  J Rheum . 1984;  1 293
    PubMedSearch in Google Scholar
  • 5 Gimovsky M L, Montoro M, Paul R H. Pregnancy outcome in women with systemic lupus erythematosus.  Obstet Gynecol . 1984;  63 686-692
    PubMedSearch in Google Scholar
  • 6 Lockshin M D, Harpel P C, Druzin M L. Lupus pregnancy: II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient.  Arthritis Rheum . 1985;  28 58-66
    PubMedSearch in Google Scholar
  • 7 McHugh N J, Reilly P A, McHugh L A. Pregnancy outcome and autoantibodies in connective tissue disease.  J Rheumatol . 1989;  16 42-46
    PubMedSearch in Google Scholar
  • 8 Mintz G, Niz J, Gutierrez G, Garcia-Alonso A, Karchmer S. Prospective study of pregnancy in systemic lupus erythematosus: results of a multidisciplinary approach.  J Rheumatol . 1986;  13 732-739
    PubMedSearch in Google Scholar
  • 9 Varner M W, Meehan R T, Syrop C H, Strottmann M P, Goplerud C P. Pregnancy in patients with systemic lupus erythematosus.  Am J Obstet Gynecol . 1983;  145 1025-1040
    PubMedSearch in Google Scholar
  • 10 Wong K L, Chan F Y, Lee C P. Outcome of pregnancy in patients with systemic lupus erythematosus: a prospective study.  Arch Intern Med . 1991;  151 269-273
    CrossrefPubMedSearch in Google Scholar
  • 11 Zulman J I, Talal N, Hoffman G S, Epstein W V. Problems associated with the management of pregnancies in patients with systemic lupus erythematosus.  J Rheumatol . 1980;  7 37-49
    PubMedSearch in Google Scholar
  • 12 Zurier R B, Argyros T G, Urman J D, Warren J, Rothfield N F. Systemic lupus erythematosus. Management during pregnancy.  Obstet Gynecol . 1978;  51 178-180
    PubMedSearch in Google Scholar
  • 13 Sittiwangkul S, Louthrenoo W, Vithayasai P, Sukitawut W. Pregnancy outcome in Thai patients with systemic lupus erythematosus.  Asian Pac J Allergy Immunol . 1999;  17 77-83
    PubMedSearch in Google Scholar
  • 14 Le Huong D, Wechsler B, Vauthier-Brouzes D. Outcome of planned pregnancies in systemic lupus erythematosus: a prospective study on 62 pregnancies.  Br J Rheumatol . 1997;  36 772-777
    CrossrefPubMedSearch in Google Scholar
  • 15 Petri M, Allbritton J. Fetal outcome of lupus pregnancy: a retrospective case-control study of the Hopkins Lupus Cohort.  J Rheumatol . 1993;  20 650-656
    PubMedSearch in Google Scholar
  • 16 Kleinman D, Katz V L, Kuller J A. Perinatal outcomes in women with systemic lupus erythematosus.  J Perinatol . 1998;  18 178-182
    PubMedSearch in Google Scholar
  • 17 Buchanan N M, Khamashta M A, Morton K E, Kerslake S, Baguley E A, Hughes G R. A study of 100 high risk lupus pregnancies.  Am J Reprod Immunol . 1992;  28 192-194
    PubMedSearch in Google Scholar
  • 18 Ginsberg J S, Brill-Edwards P, Johnston M. Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.  Blood . 1992;  80 975-980
    PubMedSearch in Google Scholar
  • 19 Lockshin M D, Druzin M L, Goei S. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus.  N Engl J Med . 1985;  313 152-156
    PubMedSearch in Google Scholar
  • 20 Ogasawara M, Aoki K, Hayashi Y. A prospective study on pregnancy risk of antiphospholipid antibodies in association with systemic lupus erythematosus.  J Reprod Immunol . 1995;  28 159-164
    PubMedSearch in Google Scholar
  • 21 Lockshin M D, Qamar T, Druzin M L. Hazards of lupus pregnancy.  J Rheumatol . 1987;  14(suppl 13) 214-217
    PubMedSearch in Google Scholar
  • 22 Englert H, Derue G, Loizou S. Pregnancy and lupus: prognostic indicators and response to treatment.  Q J Med . 1988;  250 125
    PubMedSearch in Google Scholar
  • 23 Hayslett J P, Lynn R I. Effect of pregnancy in patients with lupus nephropathy.  Kidney Int . 1980;  18 207-220
    PubMedSearch in Google Scholar
  • 24 Imbasciati E, Surian M, Bottino S. Lupus nephropathy and pregnancy: a study of 26 pregnancies in patients with systemic lupus erythematosus and nephritis.  Nephron . 1984;  36 46-51
    PubMedSearch in Google Scholar
  • 25 Jungers P, Dougados M, Pelissier C. Lupus nephropathy and pregnancy: report of 104 cases in 36 patients.  Arch Intern Med . 1982;  142 771-776
    CrossrefPubMedSearch in Google Scholar
  • 26 Fine L, Barnett E, Danovitch G. Systemic lupus erythematosus in pregnancy.  Ann Intern Med . 1981;  94 667-668
    PubMedSearch in Google Scholar
  • 27 Devoe L D, Taylor R L. Systemic lupus erythematosus in pregnancy.  Am J Obstet Gynecol . 1979;  135 473-479
    PubMedSearch in Google Scholar
  • 28 Bobrie G, Liote F, Houillier P, Grunfeld J P, Jungers P. Pregnancy in lupus nephritis and related disorders.  Am J Kidney Dis . 1987;  9 339-343
    PubMedSearch in Google Scholar
  • 29 Katz A I, Davison J M, Hayslett J P, Singson E, Lindheimer M D. Pregnancy in women with kidney disease.  Kidney Int . 1980;  18 192-206
    PubMedSearch in Google Scholar
  • 30 Surian M, Imbasciati E, Cosci P. Glomerular disease and pregnancy: a study of 123 pregnancies in patients with primary and secondary glomerular diseases.  Nephron . 1984;  36 101-105
    PubMedSearch in Google Scholar
  • 31 Aggarwal N, Sawhney H, Vasishta K, Chopra S, Bambery P. Pregnancy in patients with systemic lupus erythematosus.  Aust N Z J Obstet Gynaecol . 1999;  39 28-30
    PubMedSearch in Google Scholar
  • 32 Druzin M L, Van Vollenhoven F R. Systemic lupus erythematosus and pregnancy.  Ann Med Interne (Paris) . 1996;  147 265-273
    PubMedSearch in Google Scholar
  • 33 Kasnic T A, Wallerstedt C L, Gilson G J. Systemic lupus erythematosus in pregnancy.  J Perinat Neonat Nurs . 1997;  11 46-56
    PubMedSearch in Google Scholar
  • 34 Khamashta M A, Hughes G R. Pregnancy in systemic lupus erythematosus.  Curr Opin Rheumatol . 1996;  8 424-429
    PubMedSearch in Google Scholar
  • 35 Le Thi Huong D, Wechsler B, Piette J C, Bletry O, Godeau P. Pregnancy and its outcome in systemic lupus erythematosus.  QJM . 1994;  87 721-729
    PubMedSearch in Google Scholar
  • 36 Meng C, Lockshin M. Pregnancy in lupus.  Curr Opin Rheumatol . 1999;  11 348-351
    CrossrefPubMedSearch in Google Scholar
  • 37 Wilson W A, Gharavi A E, Koike T. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.  Arthritis Rheum . 1999;  42 1309-1311
    CrossrefPubMedSearch in Google Scholar
  • 38 Alarcon-Segovia D, Deleze M, Oria C V. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients.  Medicine (Baltimore) . 1989;  68 353-365
    PubMedSearch in Google Scholar
  • 39 Harris E N. Special report: The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group.  Am J Clin Pathol . 1990;  94 476-484
    PubMedSearch in Google Scholar
  • 40 Silver R M, Porter T F, van Leeuween I, Jeng G, Scott J R, Branch D W. Anticardiolipin antibodies: clinical consequences of ``low titers''.  Obstet Gynecol . 1996;  87 494-500
    CrossrefPubMedSearch in Google Scholar
  • 41 Branch D W. Immunologic disease and fetal death.  Clin Obstet Gynecol . 1987;  30 295-311
    PubMedSearch in Google Scholar
  • 42 Lockwood C J, Romero R, Feinberg R F, Clyne L P, Coster B, Hobbins J C. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population.  Am J Obstet Gynecol . 1989;  161 369-373
    PubMedSearch in Google Scholar
  • 43 Pattison N S, Chamley L W, McKay E J, Liggins G C, Butler W S. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations.  Br J Obstet Gynaecol . 1993;  100 909-913
    PubMedSearch in Google Scholar
  • 44 Branch D W, Silver R M, Blackwell J L, Reading J C, Scott J R. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience.  Obstet Gynecol . 1992;  80 614-620
    PubMedSearch in Google Scholar
  • 45 Cowchock F S, Reece E A, Balaban D, Branch D W, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment.  Am J Obstet Gynecol . 1992;  166 1318-1323
    PubMedSearch in Google Scholar
  • 46 Lima F, Khamashta M A, Buchanan N M, Kerslake S, Hunt B J, Hughes G R. A study of sixty pregnancies in patients with the antiphospholipid syndrome.  Clin Exp Rheumatol . 1996;  14 131-136
    PubMedSearch in Google Scholar
  • 47 Out H J, Bruinse H W, Christiaens G C. A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies.  Am J Obstet Gynecol . 1992;  167 26-32
    PubMedSearch in Google Scholar
  • 48 Lockshin M D, Druzin M L, Qamar T. Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody.  Am J Obstet Gynecol . 1989;  160 439-443
    PubMedSearch in Google Scholar
  • 49 Branch D W, Dudley D J, Mitchell M D. Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss.  Am J Obstet Gynecol . 1990;  163 210-216
    CrossrefPubMedSearch in Google Scholar
  • 50 Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies.  Proc Natl Acad Sci U S A . 1991;  88 3069-3073
    CrossrefPubMedSearch in Google Scholar
  • 51 Chamley L W, Pattison N S, McKay E J. The effect of human anticardiolipin antibodies on murine pregnancy.  J Reprod Immunol . 1994;  27 123-134
    PubMedSearch in Google Scholar
  • 52 Bakimer R, Fishman P, Blank M, Sredni B, Djaldetti M, Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).  J Clin Invest . 1992;  89 1558-1563
    CrossrefPubMedSearch in Google Scholar
  • 53 Silver R K, MacGregor S N, Sholl J S, Hobart J M, Neerhof M G, Ragin A. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.  Am J Obstet Gynecol . 1993;  169 1411-1417
    PubMedSearch in Google Scholar
  • 54 Harris E N, Spinnato J A. Should anticardiolipin tests be performed in otherwise healthy pregnant women?.  Am J Obstet Gynecol . 1991;  165 1272-1277
    PubMedSearch in Google Scholar
  • 55 Robinson R, Polzin W, Kozakowski M. The incidence of phospholipid antibodies in the obstetric population [abstract]. Proceedings of the Annual Clinical Meeting of the American College of Obstetrics and Gynecology, Las Vegas, 1992
  • 56 Haddow J E, Rote N S, Dostal-Johnson D, Palomaki G E, Pulkkinen A J, Knight G J. Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester.  Am J Obstet Gynecol . 1991;  165 1308-1312
    PubMedSearch in Google Scholar
  • 57 Infante-Rivard C, David M, Gauthier R, Rivard G E. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss: a case-control study.  N Engl J Med . 1991;  325 1063-1066
    PubMedSearch in Google Scholar
  • 58 Kutteh W H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.  Am J Obstet Gynecol . 1996;  174 1584-1589
    CrossrefPubMedSearch in Google Scholar
  • 59 Oshiro B T, Silver R M, Scott J R, Yu H, Branch D W. Antiphospholipid antibodies and fetal death.  Obstet Gynecol . 1996;  87 489-493
    CrossrefPubMedSearch in Google Scholar
  • 60 De Wolf F, Brosens I, Renaer M. Fetal growth retardation and the maternal arterial supply of the human placenta in the absence of sustained hypertension.  Br J Obstet Gynaecol . 1980;  87 678-685
    PubMedSearch in Google Scholar
  • 61 Erlendsson K, Steinsson K, Johannsson J H, Geirsson R T. Relation of antiphospholipid antibody and placental bed inflammatory vascular changes to the outcome of pregnancy in successive pregnancies of 2 women with systemic lupus erythematosus.  J Rheumatol . 1993;  20 1779-1785
    PubMedSearch in Google Scholar
  • 62 Hanly J G, Gladman D D, Rose T H, Laskin C A, Urowitz M B. Lupus pregnancy: a prospective study of placental changes.  Arthritis Rheum . 1988;  31 358-366
    CrossrefPubMedSearch in Google Scholar
  • 63 Out H J, Kooijman C D, Bruinse H W, Derksen R H. Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies.  Eur J Obstet Gynecol Reprod Biol . 1991;  41 179-186
    CrossrefPubMedSearch in Google Scholar
  • 64 Rosove M H, Tabsh K, Wasserstrum N, Howard P, Hahn B H, Kalunian K C. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies.  Obstet Gynecol . 1990;  75 630-634
    PubMedSearch in Google Scholar
  • 65 Backos M, Rai R, Baxter N, Chilcott I T, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin.  Br J Obstet Gynaecol . 1999;  106 102-107
    PubMedSearch in Google Scholar
  • 66 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;  314 253-257
    CrossrefPubMedSearch in Google Scholar
  • 67 Kaaja R, Julkunen H, Ammala P, Palosuo T, Kurki P. Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy losses associated with antiphospholipid antibodies.  Acta Obstet Gynecol Scand . 1993;  72 63-66
    CrossrefPubMedSearch in Google Scholar
  • 68 Scott J R, Branch D W, Kochenour N K, Ward K. Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization.  Am J Obstet Gynecol . 1988;  159 1055-1056
    PubMedSearch in Google Scholar
  • 69 Wapner R J, Cowchock F S, Shapiro S S. Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin infusions.  Am J Obstet Gynecol . 1989;  161 1271-1272
    PubMedSearch in Google Scholar
  • 70 Spinnato J A, Clark A L, Pierangeli S S, Harris E N. Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy.  Am J Obstet Gynecol . 1995;  172 690-694
    CrossrefPubMedSearch in Google Scholar
  • 71 Branch D W, Peaceman A M, Druzin M. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy.  Am J Obstet Gynecol . 2000;  182 122-127
    CrossrefPubMedSearch in Google Scholar
  • 72 Reece E A, Gabrielli S, Cullen M T, Zheng X Z, Hobbins J C, Harris E N. Recurrent adverse pregnancy outcome and antiphospholipid antibodies.  Am J Obstet Gynecol . 1990;  163 162-169
    PubMedSearch in Google Scholar
  • 73 Ordi J, Barquinero J, Vilardell M. Fetal loss treatment in patients with antiphospholipid antibodies.  Ann Rheum Dis . 1989;  48 798-802
    PubMedSearch in Google Scholar
  • 74 Cowchock S, Smith J B, Gocial B. Antibodies to phospholipids and nuclear antigens in patients with repeated abortions.  Am J Obstet Gynecol . 1986;  155 1002-1010
    PubMedSearch in Google Scholar
  • 75 Galli M, Comfurius P, Maassen C. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.  Lancet . 1990;  335 1544-1547
    CrossrefPubMedSearch in Google Scholar
  • 76 McNeil H P, Simpson R J, Chesterman C N, Krilis S A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H).  Proc Natl Acad Sci U S A . 1990;  87 4120-4124
    CrossrefPubMedSearch in Google Scholar
  • 77 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease [letter].  Lancet . 1990;  336 177-178
    PubMedSearch in Google Scholar
  • 78 Lubbe W F, Butler W S, Palmer S J, Liggins G C. Fetal survival after prednisone suppression of maternal lupus-anticoagulant.  Lancet . 1983;  1 1361-1363
    PubMedSearch in Google Scholar
  • 79 Chamley L W, Duncalf A M, Konarkowska B, Mitchell M D, Johnson P M. Conformationally altered beta 2-glycoprotein I is the antigen for anti-cardiolipin autoantibodies.  Clin Exp Immunol . 1999;  115 571-576
    CrossrefPubMedSearch in Google Scholar
  • 80 Aoki K, Dudkiewicz A B, Matsuura E, Novotny M, Kaberlein G, Gleicher N. Clinical significance of beta 2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems.  Am J Obstet Gynecol . 1995;  172 926-931
    CrossrefPubMedSearch in Google Scholar
  • 81 Cuadrado M J, Tinahones F, Camps M T. Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome.  QJM . 1998;  91 619-626
    CrossrefPubMedSearch in Google Scholar
  • 82 Lee R M, Emlen W, Scott J R, Branch D W, Silver R M. Anti-beta 2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome.  Am J Obstet Gynecol . 1999;  181 642-648
    PubMedSearch in Google Scholar
  • 83 Balasch J, Reverter J C, Creus M. Human reproductive failure is not a clinical feature associated with beta(2) glycoprotein-I antibodies in anticardiolipin and lupus anticoagulant seronegative patients (the antiphospholipid/cofactor syndrome).  Hum Reprod . 1999;  14 1956-1959
    CrossrefPubMedSearch in Google Scholar
  • 84 Bahar A M, Kwak J Y, Beer A E. Antibodies to phospholipids and nuclear antigens in non-pregnant women with unexplained spontaneous recurrent abortions.  J Reprod Immunol . 1993;  24 213-222
    CrossrefPubMedSearch in Google Scholar
  • 85 Kwak J Y, Gilman-Sachs A, Beaman K D, Beer A E. Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment.  Am J Obstet Gynecol. 1992;  166 1787-1795 1795 discussion-1798 discussion
    PubMedSearch in Google Scholar
  • 86 Matzner W, Chong P, Xu G, Ching W. Characterization of antiphospholipid antibodies in women with recurrent spontaneous abortions.  J Reprod Med . 1994;  39 27-30
    PubMedSearch in Google Scholar
  • 87 Ruiz J E, Cubillos J, Mendoza J C, Espinel F J, Kwak J Y, Beer A E. Autoantibodies to phospholipids and nuclear antigens in non-pregnant and pregnant Colombian women with recurrent spontaneous abortions.  J Reprod Immunol . 1995;  28 41-51
    PubMedSearch in Google Scholar
  • 88 Rote N S, Dostal-Johnson D, Branch D W. Antiphospholipid antibodies and recurrent pregnancy loss: correlation between the activated partial thromboplastin time and antibodies against phosphatidylserine and cardiolipin.  Am J Obstet Gynecol . 1990;  163 575-584
    PubMedSearch in Google Scholar
  • 89 Gharavi A E, Harris E N, Asherson R A, Hughes G R. Anticardiolipin antibodies: isotype distribution and phospholipid specificity.  Ann Rheum Dis . 1987;  46 1-6
    CrossrefPubMedSearch in Google Scholar
  • 90 Qamar T, Levy R A, Sammaritano L, Gharavi A E, Lockshin M D. Characteristics of high-titer IgG antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death.  Arthritis Rheum . 1990;  33 501-504
    PubMedSearch in Google Scholar
  • 91 el-Roeiy A, Myers S A, Gleicher N. The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women.  Obstet Gynecol . 1990;  75 390-396
    PubMedSearch in Google Scholar
  • 92 Ober C, Karrison T, Harlow L, Elias S, Gleicher N. Autoantibodies and pregnancy history in a healthy population.  Am J Obstet Gynecol . 1993;  169 143-147
    PubMedSearch in Google Scholar
  • 93 Aoki K, Hayashi Y, Hirao Y, Yagami Y. Specific antiphospholipid antibodies as a predictive variable in patients with recurrent pregnancy loss.  Am J Reprod Immunol . 1993;  29 82-87
    PubMedSearch in Google Scholar
  • 94 Kwak J Y, Gilman-Sachs A, Beaman K D, Beer A E. Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology.  J Reprod Immunol . 1992;  22 15-31
    PubMedSearch in Google Scholar
  • 95 Sugi T, Katsunuma J, Izumi S, McIntyre J A, Makino T. Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses.  Fertil Steril . 1999;  71 1060-1065
    CrossrefPubMedSearch in Google Scholar
  • 96 Branch D W, Silver R, Pierangeli S, van Leeuwen I, Harris E N. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome.  Obstet Gynecol . 1997;  89 549-555
    CrossrefPubMedSearch in Google Scholar
  • 97 Warkentin T E, Levine M N, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med . 1995;  332 1330-1335
    CrossrefPubMedSearch in Google Scholar
  • 98 Edelman P, Rouquette A M, Verdy E. Autoimmunity, fetal losses, lupus anticoagulant: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression?.  Hum Reprod . 1986;  1 295-297
    PubMedSearch in Google Scholar
  • 99 Cowchock S, Dehoratius R D, Wapner R J, Jackson L G. Subclinical autoimmune disease and unexplained abortion.  Am J Obstet Gynecol . 1984;  150 367-371
    PubMedSearch in Google Scholar
  • 100 Maier D B, Parke A. Subclinical autoimmunity in recurrent aborters.  Fertil Steril . 1989;  51 280-285
    PubMedSearch in Google Scholar
  • 101 Harger J H, Rabin B S, Marchese S G. The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses: a prospective controlled study.  Obstet Gynecol . 1989;  73 419-424
    PubMedSearch in Google Scholar
  • 102 Ogasawara M, Aoki K, Kajiura S, Yagami Y. Are antinuclear antibodies predictive of recurrent miscarriage?.  <~>[letter]. Lancet . 1996;  347 1183-1184
    PubMedSearch in Google Scholar
  • 103 Stagnaro-Green A, Roman S H, Cobin R H, el-Harazy E, Alvarez-Marfany M, Davies T F. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies.  JAMA . 1990;  264 1422-1425
    CrossrefPubMedSearch in Google Scholar
  • 104 Glinoer D, Soto M F, Bourdoux P. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.  J Clin Endocrinol Metab . 1991;  73 421-427
    CrossrefPubMedSearch in Google Scholar
  • 105 Lejeune B, Grun J P, de Nayer P, Servais G, Glinoer D. Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension.  Br J Obstet Gynaecol . 1993;  100 669-672
    PubMedSearch in Google Scholar
  • 106 Pratt D, Novotny M, Kaberlein G, Dudkiewicz A, Gleicher N. Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.  Am J Obstet Gynecol . 1993;  168 837-841
    PubMedSearch in Google Scholar
  • 107 Stricker R B. Antithyroid antibodies in recurrent pregnancy loss [letter; comment].  Am J Obstet Gynecol . 1994;  170 956-957
    PubMedSearch in Google Scholar
  • 108 Wilson R, Ling H, MacLean M A. Thyroid antibody titer and avidity in patients with recurrent miscarriage.  Fertil Steril . 1999;  71 558-561
    CrossrefPubMedSearch in Google Scholar
  • 109 Kutteh W H, Yetman D L, Carr A C, Beck L A, Scott Jr T R. Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction.  Fertil Steril . 1999;  71 843-848
    CrossrefPubMedSearch in Google Scholar
  • 110 Esplin M S, Branch D W, Silver R, Stagnaro-Green A. Thyroid autoantibodies are not associated with recurrent pregnancy loss.  Am J Obstet Gynecol . 1998;  179 1583-1586
    CrossrefPubMedSearch in Google Scholar
  • 111 Petri M, Golbus M, Anderson R, Whiting-O'Keefe Q, Corash L, Hellmann D. Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion: a controlled, prospective study of forty-four women.  Arthritis Rheum . 1987;  30 601-606
    CrossrefPubMedSearch in Google Scholar
  • 112 Barbui T, Cortelazzo S, Galli M. Antiphospholipid antibodies in early repeated abortions: a case-controlled study.  Fertil Steril . 1988;  50 589-592
    PubMedSearch in Google Scholar
  • 113 Parazzini F, Acaia B, Faden D, Lovotti M, Marelli G, Cortelazzo S. Antiphospholipid antibodies and recurrent abortion.  Obstet Gynecol . 1991;  77 854-858
    PubMedSearch in Google Scholar
  • 114 Parke A L, Wilson D, Maier D. The prevalence of antiphospholipid antibodies in women with recurrent spontaneous abortion, women with successful pregnancies, and women who have never been pregnant.  Arthritis Rheum . 1991;  34 1231-1235
    PubMedSearch in Google Scholar
  • 115 Out H J, Bruinse H W, Derksen R H. Anti-phospholipid antibodies and pregnancy loss.  Hum Reprod . 1991;  6 889-897
    PubMedSearch in Google Scholar