Namely, women with molar pregnancies have a high incidence of early-onset preeclampsia. Women with a trisomy 13 fetus also have a 30-to 40-percent incidence of preeclampsia. hese women have elevated serum levels of antiangiogenic factors. he gene for one of these factors, soluble ins-like tyrosine kinase 1, is on chromosome 13 (Bdolah, 2006). Conversely, women previ ously exposed to paternal antigens, such as a prior pregnancy with the same partner, are "immunized" against preeclampsia.
his phenomenon is not as apparent in women with a prior abortion (Strickland, 1986). Multiparas impregnated by a new consort have a greater risk of preeclampsia (Mostello, 2002).
Redman and colleagues (2015a) reviewed the possible role of immune maladaptation in preeclampsia pathophysiology. In women destined to be preeclamptic, extravillous trophoblasts early in pregnancy express reduced amounts of immunosuppressive nonclassic human leukocyte antigen G (HLA G). Black women more commonly have the 1597 �C gene allele that further predisposes to preeclampsia (Loisel, 2013). hese changes may contribute to the defective placental vascularization in stage 1 of the preeclampsia syndrome. As discussed in Chapter 4 (p. 59), T-helper (h) lymphocytes during normal pregnancy are produced so that type 2 activity is increased in relation to type 1-so-called ype 2 bias (Redman, 2012, 2015a). h2 cells promote humoral immunity, whereas Th1 cells stimulate inlammatory cytoine secretion. Beginning in the early second trimester in women who develop preeclampsia, Th1 action is increased.
Inflammatory changes are believed to be a continuation of stage 1 alterations. In response to ischemia or other inciting causes, placental factors are released and begin a cascade of events (Davidge, 2015). Thus, antiangiogenic and metabolic factors and other inflammatory leukocyte mediators are thought to provoke systemic endothelial cell injury, which is used synonymously here with endothelial cel activation or dyfunction.
Endothelial cell dysfunction may result from an extreme activated state of leukocytes in the maternal circulation (Faas, 2000; Gervasi, 2001). Briefly, cytokines such as tumor necrosis factor-a (TNF-a) and the interleukins may contribute to the systemic oxidative stress associated with preeclampsia. This is characterized by reactive oxygen species and free radicals that lead to formation of self-propagating lipid peroxides (Manten, 2005). hese peroxides in turn generate highly toxic radicals that injure systemic vascular endothelial cells, modiy nitric oxide production by these cells, and interfere with prostaglandin balance. Other consequences of oxidative stress include production of the lipid-laden macrophage foam cells seen in placental atherosis, activation of systemic microvascular coagulation manifested by thrombocytopenia, and greater systemic capillary permeability relected by edema and proteinuria.
Preeclampsia appears to be a multifactorial, polygenic disorder. In one study of almost 1.2 million Swedish births, a genetic
Data from Buurma, 2013; Staines-Urias, 2012; Triche, 2014; Ward, 2014; Ye, 2016.