Angiogenic Biomarker Placental Growth Factor (PLGF) in the Prediction and Diagnosis of Placental Dysfunction in Pre-eclampsia: A Cohort Study

Abstract

Introduction: Pre-eclampsia (PE), a pregnancy induced hypertensive disorder affects approximately 8-10% of all pregnancies in developing countries. A highly sensitive and specific marker for diagnosis of PE is the need of the hour as diagnostic criteria are still based on non-specific clinical symptoms, ultrasound, and laboratory findings. Imbalance in the placental release of various angiogenesis regulatory factors to the maternal circulation is one of the significant contributors to its clinical manifestations. Low levels of pro-angiogenic biomarker Placental Growth Factor (PLGF) are detectable several weeks before clinical presentation of PE. Aim: To determine the association of serum levels of PLGF with PE in second and third trimester of pregnancy. Materials and Methods: A prospective cohort study was performed in a tertiary care hospital from December 2018 to November 2021, on 130 patients by dividing study participants into two groups: Pre-eclamptic cases, Normotensive controls. At enrollment in second trimester (24-28 weeks) and during third trimester (beyond 28 weeks) serum PLGF concentration was measured by using the Enzyme-linked Immunosorbent Assay (ELISA) kit method. Data was statistically analysed. Student’s t-test was used for comparing differences between study groups. The chi-square test was used to compare qualitative categorical data. Evaluation of the Area Under the Curve (AUC), diagnostic accuracy, sensitivity and specificity was done by Receiver Operating Characteristics (ROC) curve analysis done using software defined cut-off values. Results: Total of 115 patients were analysed in the present study with 55 patients in group 1(mean age: 25.83±3.27 years) and 60 patients in group 2 (mean age: 30.52±5.63 years) When compared with normotensive group PLGF levels were significantly lower in pre-eclamptic group with median 16.27 ng/mL versus 12.20 ng/mL (p <0.001) in second and 14.05 ng/mL versus 10.50 ng/mL (p <0.001) in third trimesters respectively. ROC curve analysis using cut-off point of 14.91 ng/mL showed sensitivity 80%, specificity 96.7%, AUC 0.896, 95%CI:(0.832-.959) in second trimester and in third trimester at cut-off point of 13 ng/mL sensitivity 73%, specificity 96.7%, AUC 0.882 95% CI:(0.816-.948) was found. Conclusion: PLGF may be used as a biomarker for early prediction, diagnosis, and management of PE. It might serve as ideal discriminating biochemical markers of PE. In the near future, the clinical utility of disease specific angiogenic biomarker in early detection of PE might improve health outcomes by preventing adverse maternal and neonatal outcomes and serious complications.

Keywords

• angiogenic imbalance
• diagnostic marker
• maternal mortality
• pregnancy induced hypertension
• soluble fms-like tyrosine kinase-1