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Antiphospholipid Antibodies and Pregnancy: Research Review

A short overview of the impact of antiphospholipid antibodies and antiphospholipid syndrome (APS) on pregnancy - and the science behind it.

April 1, 2022 Pregmune Team
Antiphospholipid Antibodies

Phospholipids are integral components of human cell membranes. Sometimes, a person’s immune system will begin to attack its own phospholipids by developing antiphospholipid antibodies (APAs). Because blood cells contain phospholipids, APAs can lead to blood clots, miscarriages, or pregnancy complications.

Physiology

Antiphospholipid antibody syndrome (APS) is an autoantibody-mediated disorder where antiphospholipid antibodies are produced by the immune system against itself. The presence of antiphospholipid antibodies may trigger a thrombophilic disorder that causes excessive clotting and can lead to venous thromboembolism, stroke, multiple miscarriages and other pregnancy complications.

APS is considered primary if it occurs in a patient with no underlying disease and secondary if it is related to an underlying pathology such as systemic lupus erythematous (SLE). Among the different antiphospholipid antibodies, anti-beta 2 glycoprotein I (anti-β2-GP1 ) antibodies is the best to support the diagnosis of APS1. Indeed, many studies supports the fact that anti-β2-GP1 are more specific for APS than anti-cardiolipin antibodies1-3

All three isotypes of anti-β2-GP1 (IgG, IgM, and IgA) have been associated with thrombosis3-5. The presence of one or both β2-GP1 IgG and IgM antibodies is an independent risk factor for thrombosis and pregnancy complications3.

Published clinical data

APS is the most frequent acquired risk factor for recurrent pregnancy loss. Disrupting the placental function and impairing the maternal–fetal blood exchange, it also increases the risk for pregnancy complications such as stillbirth, intrauterine death, preeclampsia (PE), premature birth, and fetal growth restriction.

In RPL women, 26.4% of recurrent miscarriages were associated with the presence of anti-phospholipid antibodies6 while pregnancy complications were found in up to 20% of APS pregnancies7.

In a large meta-analysis including over 200 000 participants, the risk for spontaneous abortion in women with APS increased by a factor 2.58. Further, in a meta-analysis, moderate to high levels of anti-cardiolipin antibodies (aCL) were associated with higher risk of PE9.

When anti-phospholipid antibodies are high and persistent, there is a higher risk for preterm birth and fetal growth restriction10-11.

Ultimately, elevated titers for aCL and anti-β2GPI antibodies were associated with a 3- to 5-fold increased odd of stillbirth12.

Altogether, these studies showed that detection, close monitoring and adequate care should be given to pregnant women with APS to allow a successful pregnancy.

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References

1. Harris EN, Pierangeli SS, Gharavi AE. Diagnosis of the antiphospholipid syndrome: A proposal for use of laboratory tests. Lupus. 1998; 7(Suppl 2): S144-S148.

2. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun. 2000 Sep; 15(2):163-172.

3. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002 Mar 7; 346(10):752-763.

3. Reddel SW, Krilis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lab Immunol. 1999 Nov; 6(6):775-782. 

4. Brey RL, Abbott RD, Curb JD, et al. beta (2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: The Honolulu Heart Program. Stroke. 2001 Aug; 32(8):1701-1706.

5. Greco TP, Amos MD, Conti-Kelly AM, Naranjo JD, Ijdo JW. Testing for the antiphospholipid syndrome: Importance of IgA anti-beta 2-glycoprotein I. Lupus. 2000; 9(1):33-41. 

6. Rai RS, Regan L, Clifford K, et al. Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach. Hum Reprod 1995;10(8):2001–2005.

7. Cervera R, Serrano R, Pons-Estel GJ, et al; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015;74(6):1011–1018.

8.Liu L, Sun D. Pregnancy outcomes in patients with primary antiphospholipid syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2019 May;98(20):e15733.

9. do Prado AD, Piovesan DM, Staub HL, Horta BL. Association of anticardiolipin antibodies with preeclampsia: a systematic review and meta-analysis. Obstet Gynecol 2010;116(6):1433–1443.

10. Clark EAS, Silver RM, Branch DW. Do antiphospholipid antibodies cause preeclampsia and HELLP syndrome? Curr Rheumatol Rep 2007;9(3):219–225 54.

11. 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(2):188–195.

12. Silver RM, Parker CB, Reddy UM, et al. Antiphospholipid antibodies in stillbirth. Obstet Gynecol 2013;122(3):641–657.