Abstract
BackgroundPreeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Although predictive multiparametric screening is being developed, it is not applicable to nulliparous women, and is not applied to low-risk women. As PE is considered a heterogenous disorder, it is unlikely that any single multiparametric screening protocol containing a small group of biomarkers could have the required accuracy to predict all PE subgroups. Given the etiology of PE is complex and not fully understood, it begs the question, whether the search for biomarkers based on the predominant view of impaired placentation involving factors predominately implicated in angiogenesis and inflammation, has been too limiting. Here we highlight the enormous potential of state-of-the-art, high-throughput proteomics, to provide a comprehensive and unbiased approach to biomarker identification.Methods and findingsOur literature search identified 1336 articles; after review, 45 studies with proteomic data from PE women that were eligible for inclusion. From 710 proteins with altered abundance, we identified 13 common circulating proteins, some of which had not been previously considered as prospective biomarkers of PE. An additional search of the literature for original publications testing any of the 13 common proteins using non-proteomic techniques was also undertaken. Strikingly, 9 of these common proteins had been independently evaluated in PE studies as potential biomarkers.ConclusionThis study highlights the potential of using high-throughput data sets, which are comprehensive and without bias, to identify a profile of proteins that may improve predictions of PE and understanding of its etiology. We bring to the attention of the medical and research communities that the strengths and advantages of using data from high-throughput studies for biomarker discovery would be increased dramatically, if first and second trimester samples were collected for proteomics, and if standardized guidelines for patient reporting and data collection were implemented.
Highlights
Preeclampsia (PE), described as a syndrome that affects 5–10% of all pregnancies, remains a leading cause of maternal and perinatal morbidity and mortality [1,2,3]
Proteomics to advance the search for biomarkers in preeclampsia pregnancy-associated plasma protein-A; PE, preeclampsia; PlGF, placental growth factor; sEng, soluble endoglin; sFlt-1, soluble fms-like tyrosine kinase-1; VEGF, vascular endothelial growth factor
Clinicians predominantly rely on PE risk factors including age (>35 years), previous PE or family history, multiple gestation, BMI (>25 kg/m2), ethnicity, and whether assisted reproductive techniques were involved, leading to classification of low or high risk [9]. Clinical assessment of these risk factors has limited predictive ability [10,11] because it is not applicable to nulliparous women, and does not encompass all women who develop PE, low risk women who are not monitored as frequently. This is underscored by a recent retrospective study in which 3,230 women, of those classified as low risk pregnancies (28.7% of 10 million women), unexpectedly developed eclampsia [12]
Summary
Preeclampsia (PE), described as a syndrome that affects 5–10% of all pregnancies, remains a leading cause of maternal and perinatal morbidity and mortality [1,2,3]. The American College of Obstetricians and Gynecologists (ACOG) [6], the International Society for the Study of Hypertension in Pregnancy [7] and the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) [8] characterize PE by the presence of new onset hypertension ( 140/90 mm Hg) after 20 weeks of gestation, accompanied by at least one end organ dysfunction (e.g. kidney, liver) or fetal growth restriction (FGR). This updated criterion reflects the growing awareness of the heterogeneity of the etiology of PE. Accurate screening for PE early in pregnancy remains a significant challenge
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