The diagnostic value of placental leukemia inhibitory factor (LIF) and vascular endothelial growth factor (VEGF) levels and their combined use in the prediction of preeclampsia

Subject: Preeclampsia is one of the most important hypertensive disorders during pregnancy. It is important to detect a multisystemic, multifactorial, high-morbidity, and potentially fatal clinical condition such as preeclampsia before it is diagnosis. Currently, there is no gold standard screening test for the prediction of pre-eclampsia. In the present study, we aimed to determine the effectiveness of using LIF and VEGF molecules in predicting the development of preeclampsia. Materials and methods: In this prospective cohort study, a total of 60 pregnant women, 40 with preeclampsia and 20 without preeclampsia, who were followed up in the pregnancy outpatient clinic of Karadeniz Technical University, Department of Gynecology and Obstetrics, between 2020 and 2022, were included. The preeclampsia group was divided into four subgroups: severe or non-severe, early and late-onset. Placental tissue samples of the cases were examined. Cytoplasmic levels of LIF and VEGF were determined by immunohistochemical staining in cytotrophoblast, syncytiotrophoblast, decidual, villous stromal, and villous capillary cells and were calculated by H score. Statistical comparison was performed by ANOVA and logistic regression analyses. Sensitivity, specificity, and positive - negative predictive values were determined by ROC analysis. A multivariate logistic regression analyse was used. Results: Statistically significant differences were found in LIF and VEGF levels in the preeclampsia group compared to the control group. LIF levels of cytotrophoblast and syncytiotrophoblast were higher in the preeclampsia group. VEGF levels were higher in cytotrophoblasts, syncytiotrophoblasts and villous stromal cells in the preeclampsia group compared to the control group. No statistically significance found when early and late-onset preeclampsia compared among themselves. When LIF syncytiotrophoblast and VEGF syncytiotrophoblast levels were evaluated together, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the prediction of preeclampsia were 77.5%, 95%, 96.9% and 67.9%, respectively. When LIF cytotrophoblast and VEGF cytotrophoblast levels were evaluated together, sensitivity was found to be 82.5%, specificity 100%, positive predictive value (PPV) 100.0%, and negative predictive value (NPV) 74.1%. By taking the age or BMI as constants in multivariate logistic regression analysis, it was observed that LIF syncytiotrophoblast and VEGF syncytiotrophoblast are independent determining factors in predicting preeclampsia when LIF syncytiotrophoblast and VEGF syncytiotrophoblast are assessed alone or together. Conclusion: LIF and VEGF levels are increased in placental tissues in preeclampsia. LIF and VEGF levels are higher in cytotrophoblasts in early-onset preeclampsia and in syncytiotrophoblasts in late-onset preeclampsia. LIF levels are positively correlated with the severity of preeclampsia. We suggest that LIF and VEGF can be used alone or in combination as biomarkers for the prediction of preeclampsia.