Pre-eclampsia part 2: prediction, prevention and management

Abstract

An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences.

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

“…Uteroplacental ischemia can lead to the production of anti-angiogenic factors [103–113], such as sFlt-1 (soluble fms-like tyrosine kinase-1) [114–117] and endoglin [69,118], which can induce endothelial dysfunction and predispose to preeclampsia or an anti-angiogenic state [57,119–129]. In addition, an excess production of trophoblast debris can result in exaggerated intravascular inflammation and endothelial cell dysfunction [130–134].…”

Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study

“…There is a growing body of evidence indicating that an imbalance in maternal plasma concentrations of angiogenic and anti-angiogenic factors is characteristic of a substantial fraction of women who have or will develop preeclampsia [44, 97–107, 110, 111, 130–168], fetal death [114, 115, 169–173], SGA [64, 102–104, 117, 173–178], massive perivillous fibrin deposition [115, 178], twin-to-twin transfusion syndrome [118, 179, 180], and mirror syndrome [181]. We have also found significant differences in angiogenic marker distributions among uncomplicated pregnancies and those who are or will be affected by spontaneous PTL with intact membranes [112].…”

“…Our group demonstrated that an imbalance in maternal plasma concentrations of the angiogenic placental growth factor (PlGF) and anti-angiogenic factors [e.g., soluble vascular endothelial growth factor receptor-1 (sVEGFR-1)] is characteristic of a large fraction of women who have or will develop preeclampsia [44, 97–111]. We also found significant differences in angiogenic and anti-angiogenic factor distributions among women with uncomplicated pregnancies and those who are or will be affected by spontaneous PTL with intact membranes [112], fetal death [109, 113, 114], massive perivillous fibrin deposition [115], twin-to-twin transfusion syndrome [116], and delivery of SGA newborns [103, 117, 118].…”

“…We also found significant differences in angiogenic and anti-angiogenic factor distributions among women with uncomplicated pregnancies and those who are or will be affected by spontaneous PTL with intact membranes [112], fetal death [109, 113, 114], massive perivillous fibrin deposition [115], twin-to-twin transfusion syndrome [116], and delivery of SGA newborns [103, 117, 118]. Moreover, we reported that differences in angiogenic and anti-angiogenic factor concentrations are greater when patients with these obstetrical syndromes have placental lesions consistent with MVU [44, 109, 111]. Therefore, we hypothesize that the ratio of angiogenic to anti-angiogenic factor concentrations in maternal plasma reflects the burden of lesions consistent with MVU.…”

Gestational weight gain in Japanese women with preeclampsia

“…10 -12) Excessive GWG has been suggested to increase the risk of preeclampsia, and be associated with the inflammatory milieu, maternal body composition, body fat distribution, hyperlipidemia, insulin resistance, and coagulation abnormalities associated with the pathogenesis of preeclampsia. 13,14) However, the contribution of fluid retention secondary to edema has often been insufficiently considered in simple associations between total GWG and the prevalence of preeclampsia.…”