Antiphospholipid Antibodies and Pregnancy: Research Review

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 antibodies^1-3. 

All three isotypes of anti-β₂-GP1 (IgG, IgM, and IgA) have been associated with thrombosis^3-5. 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 restriction^10-11.

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.