Antiangiogenic Biomarker Soluble Fms-like Tyrosine Kinase-1 in Pregnancy Complicated with Preeclampsia: A Cohort Study

Abstract

Introduction: Preeclampsia (PE) is one of the leading obstetric diseases with significant morbidity and mortality in both mother and foetus. The etiology of preeclampsia is unknown. It may result from several reasons with imbalance between angiogenic regulatory factors in maternal circulation as one of the factor. High circulatory levels of Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) are detectable several weeks before clinical presentation of preeclampsia. Aim: To determine association of serum levels of sFlt-1 with preeclampsia in second and third trimester of pregnancy. Materials and Methods: A prospective cohort study was conducted in the Department of Biochemistry in collaboration with the Department of Obstetrics and Gynaecology in a tertiary care hospital (Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India), from November 2018 to March 2021. The study participants were divided into two groups i.e, normotensive (group 1) and preeclamptic (group 2). The enrollment of participants was done during second trimester. Serum sFlt-1 concentration was measured in second trimester (24-28 weeks) and in third trimester (beyond 28 weeks) using Enzyme Linked Immunoassay (ELISA) kits. Receiver Operating Characteristics (ROC) curve analysis was done for evaluation of Area Under Curve (AUC), sensitivity and specificity using software defined cut-off values. Results: Total 60 participants were there in each group with maternal mean age of 25.8±3.2 years in group 1 and 30.6±5.5 years in group 2 (p-value <0.001). sFlt-1 levels were significantly higher in preeclampsia group both in second and third trimesters when compared with normotensive group with median 313.07 versus 65.150 (p-value <0.001) and 337.875 versus 76.925 (p-value <0.001), respectively. The ROC curve analysis using 190.5 ng/mL as cut-off point in second trimester showed sensitivity 90%, specificity 85%, AUC was 0.832, 95% CI (0.745-0.918) and in third trimester at cut-off point 271.5 ng/mL showed sensitivity 90%, specificity 90%, AUC was 0.884, 95% CI (0.817-0.951). Conclusion: The soluble Fms-Like Tyrosine Kinase-1-1 (sFlt-1), may serve as biomarker for early diagnosis and can improve prediction of preeclampsia

Keywords

• angiogenic imbalance
• clinical manifestations
• diagnosis
• early prediction
• second and third trimester