Plasma Heme Scavengers Alpha-1-Microglobulin and Hemopexin as Biomarkers in High-Risk Pregnancies

Reduction of maternal mortality is a target within the Millennium Development Goals. Data on the incidence of preeclampsia and eclampsia, one of the main causes of maternal deaths, are required at both national and regional levels to inform policies. We conducted a systematic review of the incidence of hypertensive disorders of pregnancy (HDP) with the objective of evaluating its magnitude globally and in different regions and settings. We selected studies using pre-specified criteria, recorded database characteristics and assessed methodological quality of the eligible studies reporting incidence of any HDP during the period 2002-2010. A logistic model was then developed to estimate the global and regional incidence of HDP using pre-specified predictor variables where empiric data were not available. We found 129 studies meeting the inclusion criteria, from which 74 reports with 78 datasets reporting HDP were analysed. This represents nearly 39 million women from 40 countries. When the model was applied, the overall estimates are 4.6% (95% uncertainty range 2.7-8.2), and 1.4% (95% uncertainty range 1.0-2.0) of all deliveries for preeclampsia and eclampsia respectively, with a wide variation across regions. The figures we obtained give a general idea of the magnitude of the problem and suggest that some regional variations might exist. The absence of data in many countries is of concern, however, and efforts should be made to implement data collection and reporting for substantial statistics. The implementation of large scale surveys conducted during a short period of time could provide more reliable and up-to-date estimations to inform policy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances. Copyright © 2013 IFPA and Elsevier Ltd. All rights reserved.