To explore the role and clinical relevance of folate metabolites and alterations in vascular endothelial growth factor (VEGF) expression in the development and progression of early-onset preeclampsia (EOPE).

A total of 25 pregnant women with EOPE (study group) and 30 healthy full-term pregnant women (control group), who delivered at Xuzhou Maternal and Child Health Hospital from December 2020 to December 2022, were enrolled in this study. The levels of folate metabolites, including vitamin B2 (VitB2), vitamin B6 (VitB6), vitamin B9 (VitB9), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), and methionine (MET), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation analysis was used to assess the relationship between HCY and MET levels and blood pressure. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the predictive performance of each indicator for EOPE. The optimal cutoff values, sensitivity, and specificity were determined based on the maximum Youden index. This study was approved by the Ethics Committee of Xuzhou Maternal and Child Health Hospital [Approval No. XZFY2025-02-013K-01(J)].

① There were no statistically significant differences in age, gravidity, parity, or BMI between the study and control groups (P>0.05). ② VEGF levels in plasma, plasma-derived exosomes, and placental tissues were significantly lower in the study group than in the control group, with statistically significant differences between groups (P<0.05). ③ Among the folate metabolites, plasma HCY and SAM levels were significantly higher in the study group than in the control group, while plasma MET levels were significantly lower; the differences between groups were statistically significant (P<0.001). However, there were no statistically significant differences in VitB2, VitB6, VitB9, and SAH levels between the two groups (P>0.05). ④ In the study group, plasma HCY levels were positively correlated with both systolic and diastolic blood pressure (r=0.777, P=0.014; r=0.757, P<0.001); plasma MET levels were also positively correlated with systolic and diastolic blood pressure (r=0.692, P=0.039; r=0.498, P=0.019). ⑤ ROC curve analysis showed that plasma HCY and MET levels had good predictive value for the occurrence of EOPE, with AUCs of 0.887 (95%CI: 0.795-0.980, P<0.001) and 0.911 (95%CI: 0.756-1.000, P<0.001), respectively. Based on the maximum Youden index, the optimal cutoff values for HCY and MET were 3 189.50 ng/mL and 12.09 μmol/L, respectively, with sensitivities of 71.4% and 72.7%, and specificities of 71.4% and 64.4%, respectively.

Pregnant women with EOPE exhibit significant folate metabolism disorders and downregulated VEGF expression from multiple sources. Plasma HCY and SAM may serve as potential predictive indicators. Monitoring changes in these markers may aid in the early identification and risk prediction of EOPE.