Download PDF
Am J Perinatol 2018; 35(11): 1093-1099
DOI: 10.1055/s-0038-1641168
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Are Anti-β2 Glycoprotein 1 Antibodies Associated with Placenta-Mediated Pregnancy Complications? A Nested Case–Control Study

Leslie Skeith
1   Division of Hematology and Hematological Malignancies, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Karim E. Abou-Nassar
3   Service d'Hématologie et Axe de Recherche en Cancérologie, Centre Intégré de Santé et de Services Sociaux de l'Outaouais, Gatineau, Quebec, Canada
,
Mark Walker
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4   Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
,
Tim Ramsay
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Ronald Booth
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Shi Wu Wen
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4   Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
,
Graeme N. Smith
5   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada
,
Marc A. Rodger
2   Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4   Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
6   Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
› Author Affiliations Funding The OaK Birth Cohort study was funded by the Canadian Institutes of Health Research (CIHR grants # MOP 64461, MOP 82802 and MOP 53188). L.S. is the recipient of a CanVECTOR Research Fellowship award. K.E.A.-N. is the recipient of a Physicians Services Incorporated resident research grant. M.A.R. is the recipient of a Heart and Stroke Foundation Career Investigator Award (CI6225 and CI7441) and a University of Ottawa Faculty of Medicine Clinical Research Chair in Venous Thrombosis and Thrombophilia. M.W. is supported by a University of Ottawa Tier 1 Chair in Perinatal Epidemiology.
Further Information

Publication History

01 October 2017

23 February 2018

Publication Date:
10 April 2018 (online)

    Permissions and Reprints

Abstract

Background While anti-β2 glycoprotein 1 (anti-β2GP1) antibody positivity is included in the diagnostic criteria for antiphospholipid syndrome (APS), the association between anti-β2GP1 and the obstetrical complications of APS has been inconsistently reported and remains unclear.

Objective We completed a case–control study nested within the Canadian Ottawa and Kingston (OaK) Birth Cohort to evaluate the association between anti-β2GP1 antibody positivity and placenta-mediated pregnancy complications.

Study Design Five hundred cases were randomly selected among pregnant women who experienced any of the following independently adjudicated placenta-mediated pregnancy complications: preeclampsia, placental abruption, late pregnancy loss (≥ 12 weeks' gestation), and birth of a small-for-gestational age (SGA) infant < 10th percentile. Five hundred pregnant women without any placenta-mediated pregnancy complications were selected as controls. Stored blood samples were analyzed for the presence of anti-β2GP1 antibodies by enzyme-linked immunosorbent assay.

Results Anti-β2GP1 immunoglobulin G (IgG) and/or immunoglobulin M (IgM) antibodies in titers ≥ 20 G/M units (> 99th percentile) were present in 24 of 497 (4.8%) of controls and 33 of 503 (6.6%) of cases. There was no significant difference between cases and controls for the composite outcome of any placenta-mediated pregnancy complications (odds ratio, 1.38, 95% confidence interval [CI], 0.8–2.37, p = 0.25).

Conclusion Our results call into question the association between anti-β2GP1 antibodies and placenta-mediated pregnancy complications, with further research needed.

Keywords

antiphospholipid antibodies - antiphospholipid syndrome - pregnancy complications - placenta diseases - pregnancy outcome

Authors' Contributions

L.S. analyzed and interpreted data, performed statistical analysis, and wrote the first draft of the manuscript. K.E. A.-N. designed the research, analyzed and interpreted data, performed statistical analysis, and prepared the data tables. M.A.R. designed the research, collected data, analyzed and interpreted data, and performed statistical analysis. M.W. designed the research, collected data, analyzed and interpreted data, and performed statistical analysis. T.R. designed the research, analyzed, and interpreted data. R.B. designed the research and collected data. S.W.W. designed the research, collected data, analyzed and interpreted data, and performed statistical analysis. G.N.S. designed the research, collected data, analyzed and interpreted data, and performed statistical analysis. All authors reviewed drafts of the manuscript and approved the final draft of the manuscript.


 

  • References

  • 1 Abou-Nassar K, Carrier M, Ramsay T, Rodger MA. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb Res 2011; 128 (01) 77-85
    CrossrefPubMedGoogle Scholar
  • 2 Marchetti T, de Moerloose P, Gris JC. Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: the NOHA case-control study. J Thromb Haemost 2016; 14 (04) 675-684
    CrossrefPubMedGoogle Scholar
  • 3 Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G. , et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood 2014; 123 (03) 404-413
    CrossrefPubMedGoogle Scholar
  • 4 Yelnik CM, Laskin CA, Porter TF. , et al. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med 2016; 3 (01) e000131
    CrossrefPubMedGoogle Scholar
  • 5 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
    CrossrefPubMedGoogle Scholar
  • 6 Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med 2013; 368 (11) 1033-1044
    CrossrefPubMedGoogle Scholar
  • 7 Hossain N, Paidas MJ. Adverse pregnancy outcome, the uteroplacental interface, and preventive strategies. Semin Perinatol 2007; 31 (04) 208-212
    CrossrefPubMedGoogle Scholar
  • 8 Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology (Am Soc Hematol Educ Program) 2015; 2015: 53-60
    CrossrefPubMedGoogle Scholar
  • 9 Redecha P, Tilley R, Tencati M. , et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 2007; 110 (07) 2423-2431
    CrossrefPubMedGoogle Scholar
  • 10 Katano K, Aoki A, Sasa H, Ogasawara M, Matsuura E, Yagami Y. beta 2-Glycoprotein I-dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcomes in healthy pregnant women. Hum Reprod 1996; 11 (03) 509-512
    CrossrefPubMedGoogle Scholar
  • 11 Faden D, Tincani A, Tanzi P. , et al. Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correiation with pregnancy outcome. Anti-B2 glycoprotein I antibodies are associated with some obstetrical complications, mainly pre-eclampsia-eclampsia. Eur J Obstet Gynecol Reprod Biol 1997; 73 (01) 37-42
    CrossrefPubMedGoogle Scholar
  • 12 Lee RM, Emlen W, Scott JR, Branch DW, Silver RM. Anti-beta2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome. Am J Obstet Gynecol 1999; 181 (03) 642-648
    CrossrefPubMedGoogle Scholar
  • 13 Valdés-Macho E, Cabiedes J, Villa AR, Cabral AR, Alarcón-Segovia D. Anticardiolipin and anti-beta2-glycoprotein-I antibodies in hypertensive disorders of pregnancy. Arch Med Res 2002; 33 (05) 460-465
    CrossrefPubMedGoogle Scholar
  • 14 Lee RM, Brown MA, Branch DW, Ward K, Silver RM. Anticardiolipin and anti-beta2-glycoprotein-I antibodies in preeclampsia. Obstet Gynecol 2003; 102 (02) 294-300
    PubMedGoogle Scholar
  • 15 Vora S, Shetty S, Salvi V, Satoskar P, Ghosh K. A comprehensive screening analysis of antiphospholipid antibodies in Indian women with fetal loss. Eur J Obstet Gynecol Reprod Biol 2008; 137 (02) 136-140
    CrossrefPubMedGoogle Scholar
  • 16 Alijotas-Reig J, Ferrer-Oliveras R, Ruffatti A. , et al; (EUROAPS Study Group Collaborators). The European registry on obstetric antiphospholipid syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun Rev 2015; 14 (05) 387-395
    CrossrefPubMedGoogle Scholar
  • 17 Silver RM, Parker CB, Reddy UM. , et al. Antiphospholipid antibodies in stillbirth. Obstet Gynecol 2013; 122 (03) 641-657
    CrossrefPubMedGoogle Scholar
  • 18 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos A-M, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e691S-e736S
    CrossrefPubMedGoogle Scholar
  • 19 Walker MC, Finkelstein SA, Rennicks White R. , et al. The Ottawa and Kingston (OaK) Birth Cohort: development and achievements. J Obstet Gynaecol Can 2011; 33 (11) 1124-1133
    CrossrefPubMedGoogle Scholar
  • 20 Rodger MA, Walker MC, Smith GN. , et al. Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study. J Thromb Haemost 2014; 12 (04) 469-478
    CrossrefPubMedGoogle Scholar
  • 21 Kramer MS, Platt RW, Wen SW. , et al; Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics 2001; 108 (02) E35
    CrossrefPubMedGoogle Scholar
  • 22 Ferrer-Oliveras R, Llurba E, Cabero-Roura L, Alijotas-Reig J. Prevalence and clinical usefulness of antiphospholipid and anticofactor antibodies in different Spanish preeclampsia subsets. Lupus 2012; 21 (03) 257-263
    CrossrefPubMedGoogle Scholar
  • 23 Lockshin MD, Kim M, Laskin CA. , et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum 2012; 64 (07) 2311-2318
    CrossrefPubMedGoogle Scholar
  • 24 Yelnik CM, Porter TF, Branch DW. , et al. Brief Report: changes in antiphospholipid antibody titers during pregnancy: effects on pregnancy outcomes. Arthritis Rheumatol 2016; 68 (08) 1964-1969
    PubMedGoogle Scholar
  • 25 Ruffatti A, Tonello M, Visentin MS. , et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology (Oxford) 2011; 50 (09) 1684-1689
    CrossrefPubMedGoogle Scholar
  • 26 de Laat B, Pengo V, Pabinger I. , et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost 2009; 7 (11) 1767-1773
    CrossrefPubMedGoogle Scholar
  • 27 Yamada H, Atsumi T, Kobashi G. , et al. Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes. J Reprod Immunol 2009; 79 (02) 188-195
    CrossrefPubMedGoogle Scholar