One or more unexplained deaths of a morphologically normal fetus at or beyond 10 weeks of gestation (normal fetal morphology documented by ultra sound or direct examination of the fetus)
One or more premature births of a morphologically normal neonate at or before 34 weeks of gestation secondary to severe preeclampsia or placental insufficiency
Testing must be positive on two or more occasions with evaluations 12 or more weeks apart: 1.
Positive plasma levels of anticardiolipin antibodies of the IgG or IgM isotype at medium to high levels 2.
Positive plasma levels of lupus anticoagulant 3.
Anti-β2 glycoprotein-1 antibodies of the IgG or IgM isotype in titers greater than the 99th percentile
The presence of antiphospholipid antibodies (anticardiolipin or lupus anticoagulant) and anti-β2 glycoprotein-1 antibodies during pregnancy is a major risk factor for an adverse pregnancy outcome (245,246,254). In a large series of couples with recurrent abortion, the incidence of the antiphospholipid syndrome was between 3% and 5% (112). The presence of anticardiolipin antibodies among patients with known systemic lupus erythematosus portends less favorable pregnancy outcomes (255).
A number of mechanisms have been proposed by which antiphospholipid antibodies might mediate pregnancy loss (256). Antibodies against phospholipids could increase thromboxane and decrease prostacyclin synthesis within placental vessels. The resultant prothrombotic environment could promote vascular constriction, platelet adhesion, and placental infarction (257–259). Alternatively, in vitro evidence from trophoblast cell lines indicates that IgM action against phosphatidylserine inhibits formation of syncytial trophoblast (260). Syncytialization is required for proper placental function. One study demonstrated that both extravillous cytotrophoblast and syncytiotrophoblast cells synthesize β2 glycoprotein-1, the essential cofactor for antiphospholipid antibody binding (261). Although it gives insight into pathophysiology, the prognostic value of serum levels of specific antibodies against β2 glycoprotein-1 with respect to pregnancy outcome among recurrent pregnancy loss patients is contentious and may be poorer than that of standard anticardiolipin antibodies (262–264). Some have proposed that sera from antibody positive recurrent pregnancy loss patients is particularly adept at inhibiting trophoblast adhesion to endothelial cells in vitro (265). Others noted rapid development of atherosclerosis in the decidual spiral arteries of patients who test positive for antiphospholipid antibodies (266). Finally, still others have demonstrated that levels of the placental antithrombotic molecule— annexin V—are reduced within the placental villa from those women with recurrent pregnancy loss who are antiphospholipid antibody positive (267). However, placental pathologic evidence supporting causal involvement of the antiphospholipid antibody syndrome in pregnancy loss often is equivocal. The characteristic lesions for this syndrome (placental infarction, abruption, and hemorrhage) are typically missing in women with antiphospholipid antibodies, and these same pathologic lesions can be found in placentae from women with recurrent abortion who do not have biochemical evidence of antiphospholipid antibodies (256,268–270).