Endothelial activation and inflammation are major participants in the pathophysiology of the preeclampsia syndrome. As a result, compounds such as those listed in Table 40-5 are found to be elevated in circulating blood of afected women, and some have been assessed for their predictive value.
First, ibronectins are high-molecular-weight glycoproteins released from endothelial cells and extracellular matrix following endothelial injury. However, in one systematic review, neither cellular nor total ibronectin levels were clinically useful to predict preeclampsia (Leeflang, 2007).
Thrombocytopenia and platelet dysfunction are integral features of preeclampsia. Platelet activation causes augmented destruction and lower concentrations. Mean platelet volume rises because of platelet immaturity (Kenny, 2015). Although markers of coagulation activation, described earlier (p. 719), are elevated, the substantive overlap with levels in normotensive pregnant women stultiies their predictive value.
Markers of oxidative stress were also hoped to predict preeclampsia. Namely, associated higher levels of lipid peroxides coupled with decreased antioxidant activity raised this possibility. Other markers include iron, transferrin, and ferritin; resistin; hyperhomocysteinemia; blood lipids, including triglycerides, free fatty acids, and lipoproteins; and antioxidants such as ascorbic acid and vitamin E (Christiansen, 2015; CondeAgudelo, 2015; D'Anna, 2004; Mackay, 2012; Mignini, 2005). However, these have not been found to be predictive.
Last, an imbalance in antiangiogenic factors is linked to preeclampsia etiopathogenesis. For example, serum levels ofVEGF and PIGF begin to drop before clinical preeclampsia develops. And, recall from Figure 40-4 that at the same time, levels of some antiangiogenic factors, such as sFlt-1 and sEng, begin to rise (Karumanchi, 2016a; Maynard, 2008). With some of these factors, sensitivities for all cases of preeclampsia ranged from 30 to 50 percent, and specificity approximated 90 percent (Conde-Agudelo, 2015). heir predictive accuracy is higher for early-onset preeclampsia (Redman, 2015b; Tsiakkas, 2016). Determination of the sFlt-lIPIGF ratio in women admitted near 37 weeks' gestation to exclude preeclampsia was useful as a predictive factor (Baltajian, 2016; Zeisler, 2016a,b). These results suggest a clinical role for preeclampsia prediction, especially later in pregnancy (Ducworth, 2016; Gallo, 2016). They may also predict adverse pregnancy outcomes in women with lupus and comorbid anti phospholipid antibodies (Kim, 2016).
As discussed in Chapter 13 (p. 273), cell-free DNA (cfDNA) can be detected in maternal plasma. It is hypothesized that cDNA is released in preeclampsia by accelerated apoptosis of cytotrophoblasts (DiFederico, 1999). One MFMU Network study found no correlation between total cfDNA levels and preeclampsia (Silver, 2017).
Proteomic, metabolomic, and transcriptomic technologies can be employed to study serum and urinary proteins and cellular metabolites. These have opened new vistas for preeclampsia prediction, and preliminary studies indicate that these may become useful (Bahado-Singh, 2013; Carty, 2011; Ma, 2014; Myers, 2013).