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

Ellen Machado Arlindo,Rodrigo Bernardes Cardoso,Mirela Foresti Jiménez,Marcos Wengrover Rosa,Catherine Primo Nogueira De Sá,Antonio Celso Koehler Ayub,Patrícia El Beitune,Régis Kreitchmann

doi:10.1055/s-0040-1713916

Abstract

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. 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. 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). 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.

Highlights

The hypertensive disorders of pregnancy are a leading cause of maternal and perinatal mortality and morbidity worldwide, especially in developing countries, affecting 10% of pregnancies, and have been responsible for high costs to the health system.[1,2,3] Pre-eclampsia and gestational hypertension are characterized by the new onset of hypertension (> 140 mm Hg systolic or > 90 mm Hg diastolic) after 20 weeks of gestation
Decreased concentrations of the circulating proangiogenic factor placental growth factor (PlGF) and increased concentrations of the antiangiogenic factor Soluble fms-like tyrosine kinase-1 (sFlt-1) have been observed in pre-eclamptic patients, suggesting that an imbalance between these factors has a fundamental role in the pathogenesis of pre-eclampsia.[12,13,14]
Evaluation of Angiogenic Factors (PlGF and sFlt-1) in Preeclampsia Diagnosis Sá et al 699 proteinuria collection to confirm or exclude pre-eclampsia, considering this test as the evaluation parameter used in our institution for the diagnosis of the disease

Summary

Introduction

The hypertensive disorders of pregnancy are a leading cause of maternal and perinatal mortality and morbidity worldwide, especially in developing countries, affecting 10% of pregnancies, and have been responsible for high costs to the health system.[1,2,3] Pre-eclampsia and gestational hypertension are characterized by the new onset of hypertension (> 140 mm Hg systolic or > 90 mm Hg diastolic) after 20 weeks of gestation. Pre-eclampsia is diagnosed by hypertension and the coexistence of one or more of the following conditions: proteinuria (urine protein/ creatinine > 0.3 mg/mg or > 300 mg/day); maternal organ dysfunction (renal insufficiency, liver involvement, neurological complications, hematological complications); and uteroplacental dysfunction (fetal growth restriction).[4,5] often accompanied by new onset proteinuria, hypertension and other signs or symptoms of pre-eclampsia may present in some women in the absence of proteinuria.[6]. Decreased concentrations of the circulating proangiogenic factor PlGF and increased concentrations of the antiangiogenic factor sFlt-1 have been observed in pre-eclamptic patients, suggesting that an imbalance between these factors has a fundamental role in the pathogenesis of pre-eclampsia.[12,13,14] Thereby, both sFlt-1 and PlGF have been suggested to be useful for the diagnosis of pre-eclampsia

Methods

Results

Discussion

Conclusion