35. Early- and late-onset of pre-eclampsia: How do the maternal circulating biomarkers differ, and why?

Abstract

Pre-eclampsia requires the presence of placenta or residual placental compounds (as in postpartum pre-eclampsia), but the relative contribution of maternal predisposing factors versus placental factors to its pathophysiology is not well understood. The talk will revisit the classical “two-stage model” of pre-eclampsia, as proposed by Redman et al. in 1999, where incomplete placentation is the first of two stages of pre-eclampsia, typically of early onset. Maternal “intolerance” of fetal cells and failed uteroplacental spiral artery remodelling has been a proposed pathway for poor placentation, which however involves several mechanisms. The second stage comprises dysfunctional uteroplacental perfusion and placental oxidative stress, followed by secretion of inflammatory factors to the maternal circulation, with ensuing generalized maternal vascular inflammation and pre-eclampsia signs (maternal hypertension and proteinuria). We have suggested (Redman, Sargent and Staff, Placenta 2013) that the mechanisms leading to a dysfunctional uteroplacental circulation may involve additional mechanisms to poor placentation, and that syncytiotrophoblast (STB) stress, with upregulation of some proteins (as exemplified by “antioangiogenic proteins”) and downregulation of others (exemplified by “proangiogenic proteins”) is the common final pathway. We argue that maternal circulating angiogenic factors are markers of STB stress, not of preeclampsiaper se. We have proposed two major forms of placental dysfunction in pre-eclampsia: one extrinsic (poor placentation) and one intrinsic cause (villous overcrowding). Our model explains important differences of early- and late-onset pre-eclampsia, including their relation to maternal circulating placenta-associated proteins used as biomarkers for the syndrome (Redman and Staff, AJOG 2015). The talk will also argue that there is no condition such as “maternal” pre-eclampsia, as all pre-eclampsia originate in the placenta. We suggest however that maternal factors may contribute two both stages of pre-eclampsia, the first by affecting either placental pathways to STB stress and the latter by amplifying the effects of STB stress on maternal vasculature.