Molecular markers of the second wave of trophoblast invasion as predictors of chronic placental insufficiency

BACKGROUND: Chronic placental insufficiency is a key factor of perinatal morbidity and mortality. This condition is caused by a disruption of the second wave of trophoblast invasion, accompanied by a deficiency in angiogenesis and activation of the hemostatic system. Currently, the possibility of early detection of women with a high risk of developing chronic placental insufficiency before clinical manifestations occur is of particular interest.

AIM: The aim of this study was to develop and validate a mathematical model at the stage of the second wave of trophoblast invasion (16–18 weeks of pregnancy) based on the assessment of immunological, angiogenic and coagulological markers for predicting the high risk of developing chronic placental insufficiency in women.

METHODS: This cross-sectional single-center study included pregnant women with complicated obstetric history. The levels of D-dimer, antithrombin III, soluble fms-like tyrosine kinase-1 activity / placental growth factor ratio, and antibodies to phospholipids were assessed in the study groups. The logistic regression method was used to build a prognostic model. Model performance was assessed by sensitivity, specificity, and area under the ROC curve.

RESULTS: This study enrolled 462 pregnant women. With a probability threshold of ≥0.332, the model demonstrated a sensitivity of 87.5%, a specificity of 75.0%, and AUC of 0.838 (p < 0.05). A relationship was found between the angiogenesis and coagulation profile parameters.

CONCLUSION: The developed mathematical model allows for highly accurate prediction of the risk of developing chronic placental insufficiency in the second wave of trophoblast invasion. Its use in clinical practice may contribute to early detection of high-risk patients and timely initiation of preventive therapy aimed at improving placental perfusion and reducing perinatal complications.