Biomarker development for presymptomatic molecular diagnosis of preeclampsia: feasible, useful or even unnecessary?

Abstract

The past decade saw the advent of a number of promising biomarkers to detect pregnancies at risk for preeclampsia (PE), the foremost being those associated with an imbalance of angiogenic factors. In late pregnancy, these are useful for the detection of imminent cases of PE, while earlier they were more predictive for early- than late-onset PE. This suggests that there may be fundamental differences between the underlying pathology of these two PE forms. Therefore, it is possible that such a biological premise may limit the development of biomarkers that will permit the efficacious detection of both early- and late-onset PE via an analysis of first-trimester maternal blood samples. Consequently, a significant increase in our understanding of the underlying pathology of PE, using a variety of approaches ranging from systems biology to animal models, will be necessary in order to overcome this obstacle.

Multimodal Regulation of NET Formation in Pregnancy: Progesterone Antagonizes the Pro-NETotic Effect of Estrogen and G-CSF

“…The possible involvement of overtly activated neutrophils in the etiology of PE was further supported by the detection of large numbers of NETs in the intervillous space of affected placentae (10). Furthermore, data from animal models suggested that tissue-resident proangiogenic decidual neutrophils (42) and activation of circulatory neutrophils via the complement cascade may contribute to PE-like conditions or those associated with fetal loss (43, 44). The latter is supported by recent reports that antiphospholipid antibodies, which are frequently detected in cases with recurrent fetal loss, trigger NETosis [reviewed in Ref.…”

A Dormant Microbial Component in the Development of Preeclampsia

“…Because of the lengthy development of PE during pregnancy, there has long been a search for biomarkers (somewhat equivalent to the “risk factors” discussed earlier) that might have predictive power, and some of these, at both metabolome (15, 654–661) and proteome (662–667) level, are starting to come forward. The typical experimental design is a case–control, in which markers that are raised or lowered significantly relative to the age-matched controls are considered to be candidate markers of PE.…”

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

“…51 Only the end stage of the disease is examined in placental analysis, and causative factors may have been masked by the overreaching consequences of placental hypoxia and in ammation. 165 It might be possible to obtain samples of chorionic villi as is used in detection of aneuploidy at the end of the rst trimester. 166 This method would allow research into causative factors.…”

“…However it su ers from the same problem as other rst trimester research; the incidence rate of the disease demands a very large biobank which would also contain a large degree of chromosomal disorders due to the indications for chorionic villi sampling. 165 …”

“…168 Late onset preeclampsia is often referred to as the milder disease, but is in fact responsible for the majority of preeclampsia-related maternal deaths worldwide. 165 Severe gestational hypertension has higher rates of adverse perinatal outcomes than moderate preeclampsia. 185 Although much research has focused on prediction of early onset preeclampsia, there is also a critical need for prediction of late onset disease and gestational hypertension.…”