Evaluation of Angiogenic Factors (PlGF and sFlt-1) in Pre-eclampsia Diagnosis

Abstract

Objective Recent observations support the hypothesis that an imbalance between angiogenic factors has a fundamental role in the pathogenesis of pre-eclampsia and is responsible for the clinical manifestations of the disease. The goal of the present study was to evaluate the sensitivity, specificity, and the best accuracy level of Soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in maternal serum and protein/creatinine ratio in urine sample to define the best cutoff point of these tests to discriminate between the patients with gestational hypertension and the patients with pre-eclampsia, to evaluate the possibility of using them as diagnostic methods. Methods A prospective longitudinal study was performed, and blood samples were collected from 95 pregnant patients with hypertension to measure serum concentrations of biomarkers sFlt-1 and PlGF. Urine samples were collected for protein screening. Significance was set as p < 0.05. Results The sFlt-1/PlGF ratio demonstrated a sensitivity of 57.5% and a specificity of 60% using 50.4 as a cutoff point. The test that showed the best accuracy in the diagnosis of pre-eclampsia was protein/creatinine ratio, with a sensitivity of 78.9% and a specificity of 70% using 0.4 as a cutoff point and showing an area under the receiver operating characteristic curve of 0.80 (p < 0.001). Conclusion No studied laboratory test proved to be fairly accurate for the diagnosis of pre-eclampsia, except for the protein/creatinine ratio. The evidence is insufficient to recommend biomarkers sFlt-1 and PlGF to be used for the diagnosis of pre-eclampsia.

Evaluation of the angiogenic factors sFlt‐1, PlGF, and the sFlt‐1/PlGF ratio in preeclampsia and associated features

“…42 In contrast to our finding, a recent Brazilian study concluded that the evidence was insufficient for the use of sFlt-1 and PlGF in PE diagnosis. 16 The apparent contradictions between our findings and other studies are attributed to differences in the sample size, ethnic/racial background, and technical differences. 24,43 Moreover, the gestational age, the analyte type (total vs. free fraction), and the definition of PE were not uniform among all reported studies.…”

“…In addition, a US study suggested that ratios were lower than those among women in whom term preeclampsia later developed at 33 through 36 weeks ( P = 0.006) and 37 through 42 weeks ( P = 0.004) 42 . In contrast to our finding, a recent Brazilian study concluded that the evidence was insufficient for the use of sFlt‐1 and PlGF in PE diagnosis 16 . The apparent contradictions between our findings and other studies are attributed to differences in the sample size, ethnic/racial background, and technical differences 24,43 …”

“…10,14,43 Normal pregnancy is linked with a fine balance between sFLT-1 and PlGF levels. This balance is disrupted in PE, 6,16,35 causing damage to the placental vasculature, leading to reduced blood flow and hypoxia. 7,17 Correlation studies were performed for assessing the effect of sFLT-1, PlGF, and their ratio on maternal (dysmenorrhea, hypertension, C-section delivery) and baby (APGAR score, baby weight) outcomes.…”

“…These angiogenic factors can be monitored in plasma or serum, and the ratio of sFlt‐1/PlGF is used as an indicator of the state of angiogenesis 10,15 . The varied serum levels of sFlt‐1 and PlGF linked with overt PE, even before its onset, assign a diagnostic/prognostic role of these factors in PE diagnosis according to the timing (early onset vs. late‐onset) and development of complications 10,16–18 . Lower PlGF levels combined with relatively high sFlt1 levels were reported in PE cases compared to women with uncomplicated pregnancies 14,18,19 .…”

“…10,15 The varied serum levels of sFlt-1 and PlGF linked with overt PE, even before its onset, assign a diagnostic/prognostic role of these factors in PE diagnosis according to the timing (early onset vs. late-onset) and development of complications. 10,[16][17][18] Lower PlGF levels combined with relatively high sFlt1 levels were reported in PE cases compared to women with uncomplicated pregnancies. 14,18,19 Other studies have shown that a heightened sFlt-1/PlGF ratio precipitates an enhanced risk of PE, but there are racial-ethnic differences in the secretion of mid-trimester maternal levels of these factors.…”