Pro-angiogenic vascular endothelial growth factor (VEGF), placental growth factor (PIGF) and anti-angiogenic factor, soluble FMS like tyrosine kinase-1 (sFlt-1) in preeclampsia – A case control study

Abstract

Background: Pregnancies that are complicated by Preeclampsia (PE) range from three to eight percent. Perinatal and neonatal mortality rate is about ten percent worldwide in developing countries due to PE. This is a multisystem disorder that leads to an increase in maternal and fetal morbidity and mortality. PE is due to impaired placentation that results in placental hypoxia, and endothelial dysfunction, It is characterized by decreased maternal circulating pro-angiogenic proteins like vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), increased anti-angiogenic proteins sFlt-1, before the onset of clinical signs of PE. Oxidative stress also is implicated in the pathogenesis of PE. Studies have demonstrated low VEGF, PlGF, sFlt-1 and sFlt-1: PIGF ratio as a PE predictor but the clinical utility of these parameters is not yet generally established and only few studies have focused on neonatal outcomes. Aim: The aim of the study was to determine diagnostic criteria for diagnosis of PE using pro-angiogenic VEGF, PIGF and anti-angiogenic sFlt-1 factors. Objectives: The present study was undertaken to compare maternal VEGF, PIGF, sFlt-1 and sFlt-1:PIGF ratio in PE and normal healthy pregnant women, know the correlation between VEGF, PIGF, sFlt-1 and sFlt-1:PIGF ratio with severity of PE, to find its best cut-off value of these parameters for diagnosis of PE by ROC curve analysis and to study association with neonatal birth weight and APGAR score. Methods: This was a case control study, conducted at tertiary care hospital, in Karnataka, India. The study was approved by Institutional ethics committee. Informed consent was obtained from all the participants. Forty singleton primigravida pregnant women aged 18-35 years, 20 or more weeks of gestation, diagnosed as PE andclassified as mild/severe PE and 40 healthy pregnant women as controls were selected for the study, based on America college of obstetricians and gynecologists guidelines. VEGF, PIGF and sFlt-1 were estimated by ELISA method. All the participants were visited again to note the neonatal birth weight and APGAR score. Analysis was done using SPSS software version 19. Results: Maternal serum VEGF and PIGF were significantly (p=0.0003, p<0.0001respectively) higher in PE patients than controls and there was significant decrease in mild PE than severe PE (p=0.0465, p=0.0049 respectively) patients. Maternal serum sFlt-1 and sFlt-1:PIGF ratio were significantly higher (p<0.0001) in PE patients than normal healthy pregnant women. Best cut-off value of VEGF, PIGF, sFlt-1 and sFlt-1:PIGF ratio were 150.0 pg/ml, 105.65 pg/ml, 1843 pg/ml and 28.54 respectively , and under the curve were 0.734, 0.802, 0.945 and 0.922. Birth weight and APGAR score had significant (p=0.000) correlation with sFlt-1 and sFlt-1:PIGF ratio. Conclusion: There was a significant decrease in angiogenic factors, significant increase in anti-angiogenic factor and sFlt1:PIGF ratio in PE than healthy pregnant women. There was significant correlation between severity of PE and PIGF, sFlt1 and sFlt-1:PIGF ratio. PIGF, sFlt1 and sFlt-1:PIGF ratio with mentioned cut-off values are better markers and can be used as diagnostic markers in PE. PIGF, sFlt1 and the ratio can be used as prognostic markers with mentioned criterion values for immediate birth outcomes.