How to identify pregnant women at risk of pre-eclampsia? — a review of the current literature

Preeclampsia (PE), a multisystem disorder in pregnancy, is a main cause of perinatal mortality and is associated with long-term maternal complications. For a long time, PE was defined as the new onset hypertension and proteinuria after 20 weeks’ gestation. It had been shown that this “gold standard definition” is not able to provide a sufficient prediction of PE-related fetal and/or maternal complications. In 2018 the International Society for the Study of Hypertension in Pregnancy recommended a broader definition of the disease. The new definition of the International Society for the Study of Hypertension in Pregnancy ruled out proteinuria as mandatory for the diagnosis of PE. This new definition increases the number of patients diagnosed as preeclamptic by nearly 21%, which is not accompanied by an increased severity of maternal outcomes. Including angiogenic biomarkers, however, has been shown to increase detection of adverse outcomes. The pathophysiology of PE is complex and not yet completely explained. Advances in prediction and diagnosis have been achieved by discovery and clinical evaluation of biomarkers, especially of placental origin. A broad spectrum of biomarkers has been tested, a few of them have been introduced into the clinical practice as of today. Especially angiogenic biomarkers that are rooted in the pathophysiology of PE have been demonstrated to be important in the prediction and diagnosis of adverse outcomes. At a cut-off value of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF)-ratio of 85, early-onset PE <34+0 weeks of gestation can accurately be diagnosed with a sensitivity of 89% and a specificity of 97%. The Prediction of short-term outcome in pregnant women with suspected preeclampsia (PROGNOSIS) study has shown that the high negative predictive value (99.3%) of the sFlt-1/PlGF-ratio below 38 in patients with suspected PE rules out the onset of the disease within one week. PROGNOSIS Asia, evaluating the sFlt-1/PlGF-ratio cut-off of 38 in an Asian population, confirmed the excellent accuracy in prediction. Recently, the angiogenic biomarkers have been integrated in multi-marker prediction models. Digital approaches, integrating algorithm-based decision support tools paired with home monitoring devices may be the next step in enhancing predictive accuracy and thus bear the potential to reduce maternal and/or fetal morbidity and mortality and save costs for the payer in parallel. The objective of this review is to provide an overview of current methods for predicting and diagnosing PE.

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Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

Fedotov,

Khrabrova,

Vashukova

et al. 2024

PLoS ONE

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Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30–100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

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How to identify pregnant women at risk of pre-eclampsia? — a review of the current literature

Cited by 4 publications

References 21 publications

CXCL9/CXCL10 angiostasis CXC-chemokines in parallel with the CXCL12 as an angiogenesis CXC-chemokine are variously expressed in pre-eclamptic-women and their neonates

CXCL9/CXCL10 angiostasis CXC-chemokines in parallel with the CXCL12 as an angiogenesis CXC-chemokine are variously expressed in pre-eclamptic-women and their neonates

Short Term Prediction of Preeclampsia

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

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