探讨孕妇各种血浆叶酸代谢物异常与血浆、血浆外泌体及胎盘组织中血管内皮生长因子(VEGF)水平变化，在孕妇早发型子痫前期(EOPE)发生、发展中的作用及相关性分析。

选择2020年12月至2022年12月在徐州市妇幼保健院分娩的25例EOPE孕妇(研究组)及30例健康足月分娩孕妇(对照组)为研究对象。采用超高效液相色谱-串联质谱(UPLC-MS/MS)法检测2组孕妇的各种血浆叶酸代谢物水平，包括维生素B2(VitB2)，维生素B6(VitB6)，维生素B9(VitB9)，S-腺苷甲硫氨酸(SAM)，S-腺苷高半胱氨酸(SAH)、同型半胱氨酸(HCY)及甲硫氨酸(MET)。采用Spearman相关性分析，评估孕妇血浆叶酸代谢物HCY和MET与孕妇血压间的相关性。通过绘制孕妇各种血浆叶酸代谢物水平的受试者工作特征(ROC)曲线，并计算曲线下面积(AUC)，评估上述各指标对EOPE孕妇的预测效能，并根据约登指数最大原则，确定诊断孕妇发生EOPE的最佳临界值、敏感度及特异度。本研究经徐州市妇幼保健院伦理委员会批准[批准文号：XZFY2025-02-013K-01(J)]。

①研究组和对照组孕妇年龄、孕次、产次及人体质量指数(BMI)比较，差异均无统计学意义(P>0.05)。②研究组孕妇血浆、血浆外泌体及胎盘组织中VEGF水平，均显著低于对照组，并且差异均有统计学意义(P<0.05)。③研究组孕妇血浆叶酸代谢物中血浆HCY、SAM水平，均较对照组显著升高，而血浆MET水平，则较对照组显著降低，并且差异亦均有统计学意义(P<0.001)。2组孕妇血浆叶酸代谢物中，VitB2、VitB6、VitB9及SAH水平比较，差异均无统计学意义(P>0.05)。④研究组孕妇血浆叶酸代谢物中HCY水平，分别与孕妇的收缩压和舒张压呈正相关关系(r＝0.777、P＝0.014，r＝0.757、P<0.001)；孕妇血浆叶酸代谢物中MET水平，也与其收缩压和舒张压呈正相关关系(r＝0.692、P＝0.039，r＝0.498、P＝0.019)。⑤孕妇各种血浆叶酸代谢物水平的ROC曲线分析结果显示，HCY和MET水平对EOPE发生具有较好预测价值，均为EOPE发生的独立影响因素(ROC-AUC＝0.887，95%CI：0.795~0.980，P<0.001；ROC-AUC＝0.911，95%CI：0.756~1.000，P<0.001)，根据约登指数最大原则，HCY和MET水平对预测孕妇EOPE发生的最佳临界值分别是3 189.50 ng/mL和12.09 μmol/L，其预测叶酸代谢异常孕妇发生EOPE的敏感度分别为71.4%和72.7%，特异度分别为71.4%和64.4%。

EOPE孕妇存在明显叶酸代谢紊乱伴多来源VEGF(来源于孕妇血浆、血浆外泌体及胎盘组织中)表达下调，其中血浆叶酸代谢物HCY和SAM，可作为孕妇发生EOPE的潜在预测指标。因此，监测多来源VEGF水平变化或有助于叶酸代谢异常孕妇发生EOPE的早期诊断与风险预测。

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.