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Objective: To investigate the relationship between serum 25-hydroxyvitamin D [25 (OH)D], insulin growth factor binding protein 1 (IGFBP-1), signal transducer and activator of transcription 4 (STAT4) and spontaneous abortion in patients with severe preeclampsia (PE). Methods: 150 severe PE patients who were treated in the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2022 were selected. Patients were divided into occurrence group (n=41) and non-occurrence group (n=109) according to whether spontaneous abortion occurred within 28 weeks of pregnancy. The levels of serum 25 (OH)D, IGFBP-1 and STAT4were compared between two groups. The clinical data in two groups were collected, and the influencing factors of spontaneous abortion in severe PE patients were analyzed by multivariate Logistic regression. The predictive value of serum 25 (OH)D, IGFBP-1 and STAT4 levels for spontaneous abortion in severe PE patients were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of 25 (OH)D and IGFBP-1 in occurrence group were lower than those in non-occurrence group, and the level of STAT4 was higher than that in non-occurrence group (P＜0.05). Spontaneous abortion in severe PE patients was not related to age, gestational age of PE onset, pre-pregnancy body mass index (BMI), delivery history, systolic blood pressure (SBP), diastolic blood pressure (DBP), platelet count (PLT) and creatinine (Scr) (P＞0.05), but was related to abortion history, D-dimer (D-D), albumin (ALB), homocysteine (Hcy) and fibrinogen (P＜0.05). Multivariate logistic regression analysis showed that, the decrease of 25 (OH)D, the decrease of IGFBP-1, the increase of STAT4, abortion history, the increase of D-D, the decrease of ALB and the increase of Hcy were the risk factors of spontaneous abortion in severe PE patients, while the increase of fibrinogen was the protective factor of spontaneous abortion in severe PE patients (P＜0.05). The area under the curve (AUC) of combined detection of serum 25 (OH)D, IGFBP-1 and STAT4 in predicting spontaneous abortion was 0.960, which was higher than that of single index prediction. Conclusion: The decrease of serum 25 (OH)D and IGFBP-1 and the increase of STAT4 level in severe PE patients are likely to lead to spontaneous abortion, the occurrence of spontaneous abortion is also relate to abortion history, D-D, ALB, Hcy, fibrinogen level and other factors. [ABSTRACT FROM AUTHOR]