The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia
ABSTRACT An imbalance in circulating factors that regulate blood vessel formation and health, referred to as angiogenic factors, plays a central role in the pathogenesis of preeclampsia.
Several studies have demonstrated a strong association between altered circulating angiogenic factors and preeclampsia. These factors include circulating antiangiogenic proteins such as soluble fms-like tyrosine kinase 1 and soluble endoglin and proangiogenic protein such as placental growth factor. Abnormalities in these circulating angiogenic factors are not only present during clinical disease, but also antedate clinical signs and symptoms by several weeks. These alterations are particularly prominent in patients who present with preeclamptic signs and symptoms prematurely and/or in patients with severe preeclampsia. The availability of automated platforms for the rapid measurement of circulating angiogenic proteins in blood samples has now allowed researchers and clinicians to evaluate the utility of these assays in the diagnosis of the disease, in the stratification of patients in clinical trials, or in the monitoring of therapies. In this review we highlight the various studies that have been performed, with a focus on large validation studies.
Measurement of circulating angiogenic proteins for the diagnosis and prediction of preeclampsia is still at an early stage but is rapidly evolving. Standardization across the various automated platforms and prospective studies that demonstrate clinical utility are needed.
- SourceAvailable from: Faustino R Perez-Lopez[Show abstract] [Hide abstract]
ABSTRACT: Background: Higher 1 st trimester maternal serum levels of interferon-induced protein 10 (IP-10) and interferon inducible T-cell alpha chemoattractant (ITAC) are reported in gestations complicated with preeclampsia. However, parallel results in the fetal circulation are lacking. Objective: To compare IP-10 and ITAC levels in neonatal cord blood from gestations complicated by severe preeclampsia vs. gestational age-matched controls. Method: Umbilical cord vessels were sampled following delivery of women with severe preeclampsia (n = 30) ≥ 36 weeks to measure plasma IP-10 and ITAC levels and compared to corresponding controls matched for parity as well as maternal and gestational age. Chemokines were measured by specific ELISAs and expressed as pg/mL. Rho Spearman ’ s coefficients were calculated to establish correlations between chemokine values and various numeric variables. Results: Preeclamptic cases displayed significantly lower median plasma umbilical artery and vein levels of both chemokines when compared to controls (IP-10: 23.4 vs. 31.4 and 2.0 vs. 24.6 pg/mL, P < 0.05; and ITAC: 2.0 vs. 13.9 and 11.9 vs. 31.6 pg/mL, P < 0.05, in artery and vein, respectively). There was a significant correlation between levels of both chemokines (r 2 = 0.616, P = 0.0001), but not with other variables. Conclusion: In contrast to elevated 1 st trimester levels of IP-10 previously found in the maternal serum of women who later developed preeclampsia, this study found lower umbilical cord IP-10 and ITAC plasma levels in near-term gestations with established severe preeclampsia.Journal of Perinatal Medicine 05/2015; DOI:10.1515/jpm-2014-0371 · 1.43 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This study was undertaken to investigate the usefulness of standard biochemical and hematological parameters measurement at third trimester of pregnancy for the individual prediction of preeclampsia. A retrospective designed study included 113 patients with preeclampsia and a control group of 95 normal, uncomplicated pregnancies. Patients were recruited in the third trimester of pregnancy at the Department of Gynecology and Obstetrics, General Hospital Celje, Slovenia, EU. Erythrocytes, leukocytes, thrombocytes, hemoglobin, hematocrit, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, urea, creatinine, uric acid, body mass index, parity, and age were evaluated to predict the occurrence of preeclampsia based on multivariate logistic regression model. When parameters such as uric acid and urea were included into logistic regression model, we correctly classified 79.6% patients. With additional four parameters (thrombocytes, hematocrit, aspartate aminotransferase and leukocytes) we correctly classified 83.8% patients with preeclampsia. Our findings confirmed that several standard biochemical and hematological parameters, when used as laboratory test panel have significant prognostic value in the prediction of preeclampsia.The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2009; 23(1):96-102. DOI:10.3109/14767050903156643 · 1.21 Impact Factor
Article: The need to redefine preeclampsia.[Show abstract] [Hide abstract]
ABSTRACT: Introduction: The current definition of preeclampsia is based on convention and not on maternal and/or perinatal outcomes. This article reviews some of the limitations of the conventional definition of preeclampsia and recent evidence suggesting that there is a dose-response relationship between the magnitude of uteroplacental ischemia and the timing of onset of preeclampsia. Areas covered: This clinical opinion reviews the limitations of the conventional cutoff for 24-h proteinuria during pregnancy, problems with blood pressure measurement in pregnant women and recent insights into the pathophysiology of preeclampsia including the role of angiogenic imbalances. Expert opinion: New criteria to redefine preeclampsia has to rely on studies that compare the degree of proteinuria, the severity of hypertension and perhaps the magnitude of angiogenic imbalances in relation with maternal and/or perinatal outcomes. We propose a hypothetical sub-classification of preeclampsia according to whether there is evidence of absolute or relative uteroplacental ischemia in view of the lack of placental pathology support for the cutoff of 34 weeks to sub-classify preeclampsia.Expert Opinion on Medical Diagnostics 07/2012; 6(4):347-357. DOI:10.1517/17530059.2012.691093