A non-invasive and convenient pregnancy outcome prediction model for URSA: based on the characteristics of maternal peripheral blood inflammatory cytokines

Abstract Introduction: Recurrent unexplained miscarriage (URSA), which accounts for over 50% of recurrent abortion cases, is closely associated with maternal immune dysregulation, particularly an imbalance of inflammatory cytokines. However, the prognostic value of peripheral blood cytokine profiles in predicting outcomes of URSA remains incompletely elucidated. This study aimed to construct and validate a prediction model based on peripheral blood inflammatory cytokine levels to non-invasively assess the risk of pregnancy outcomes in patients with unexplained recurrent spontaneous abortion (URSA). Methods: A retrospective study design was adopted, enrolling 138 URSA patients and 124 healthy controls from the reproductive medicine outpatient department of Fujian Provincial Maternity and Children's Hospital between January 2020 and December 2024. By detecting the levels of 12 serum inflammatory cytokines, differences were compared between healthy controls and URSA patients, as well as between URSA patients with good and poor prognosis. LASSO analysis and logistic regression analysis were used to develop the model, which was validated in a training set (70%) and an internal validation set (30%). The model's performance, discriminative ability, and clinical applicability were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the model was visualized by constructing nomograms. Results: Significant differences in pro-inflammatory cytokines TNF-α, IFN-γ, IL10, IL6, and IL8 were observed among the normal control group, the URSA group, and the two URSA outcome groups. Among these, URSA patients with elevated TNF-α and IFN-γ levels and decreased IL10 levels had a significantly increased risk of miscarriage. A prediction model was developed based on these findings, with an AUC value of 0.887 (95% CI: 0.784–0.991). Conclusion: The pregnancy outcomes of URSA patients are closely related to the levels of peripheral blood inflammatory cytokines TNF-α, IFN-γ, and IL10. Elevated IFN-γ and TNF-α, along with decreased IL-10, are important markers of a poor prognosis.