血清VEGF、sFlt-1、IL-4水平与妊娠期高血压疾病患者预后的关系研究

摘要 目的：探讨血清血管内皮生长因子（VEGF）、可溶性Fms样酪氨酸激酶-1（sFlt-1）、白细胞介素-4（IL-4）水平与妊娠期高血压疾病（HDP）患者分类及妊娠结局的关系。方法：选取2019年7月～2021年1月我院收治的204例HDP患者（HDP组），根据指南分类原则分为妊娠期高血压组（n=88）、子痫前期组（n=66）、子痫组（n=50），根据妊娠结局分为结局不良组和结局良好组，另选取同期100名于我院产检健康孕产妇为对照组。采用单因素及多因素Logistic回归和受试者工作特征（ROC）曲线分析HDP患者妊娠结局不良的影响因素及血清VEGF、sFlt-1、IL-4水平对妊娠结局不良的预测价值。结果： 与对照组比较，HDP组血清VEGF、IL-4水平降低，sFlt-1水平升高（P＜0.05）。妊娠期高血压组、子痫前期组、子痫组血清VEGF、IL-4水平依次降低，sFlt-1水平依次升高（P＜0.05）。204例HDP患者妊娠结局不良发生率为29.90%（61/204）。单因素分析显示，妊娠结局不良与年龄、不同疾病分类、SBP、DBP、尿蛋白、VEGF、sFlt-1、IL-4有关（P＜0.05）。多因素Logistic回归分析显示，HDP患者妊娠结局不良的独立危险因素与独立保护因素分别为子痫、sFlt-1升高与VEGF、IL-4升高（P＜0.05）。血清VEGF、sFlt-1、IL-4水平单独与联合预测HDP患者妊娠结局不良的曲线下面积（AUC）分别为0.766、0.774、0.770、0.905，VEGF、sFlt-1、IL-4联合预测HDP患者妊娠结局不良的AUC最大。结论：HDP患者血清VEGF、IL-4水平降低，sFlt-1水平升高，与HDP分类和妊娠结局不良有关，VEGF、sFlt-1、IL-4联合对HDP患者妊娠结局不良的预测价值较高。

Study on the Relationship between Serum VEGF, sFlt-1 and IL-4 Levels and the Severity and Prognosis of Patients with Hypertensive Disorders in Pregnancy

ABSTRACT Objective: To investigate the relationship between serum vascular endothelial growth factor (VEGF), soluble Fms-like tyrosine kinase-1 (sFlt-1) and interleukin-4 (IL-4) levels and the classification and pregnancy outcome of patients with hypertensive disorders of pregnancy (HDP). Methods: A total of 204 patients with HDP admitted to our hospital from July 2019 to January 2021 (HDP group) were selected and divided into pregnancy induced hypertension group (n=88), pre-eclampsia group (n=66), and eclampsia group (n=50) according to the guideline classification, and divided into poor outcome group and good outcome group according to the pregnancy outcome, and another 100 healthy pregnant women who delivered in our hospital during the same period were selected as the control group. Univariate and multivariate Logistic regression and receiver working characteristics (ROC) curves were used to analyze the influence factors of adverse pregnancy outcomes in HDP patients and the predictive value of serum VEGF, sFlt-1 and IL-4 levels. Results: Compared with the control group, the levels of serum VEGF and IL-4 in the HDP group decreased, the level of sFlt-1 increased (P<0.05). Serum VEGF and IL-4 levels decreased and sFlt-1 levels increased sequentially in the gestational hypertension, preeclampsia and eclampsia groups (P<0.05). The incidence of adverse pregnancy outcomes in 204 HDP patients was 29.90% (61/204). Single factor analysis showed, poor pregnancy outcomes were associated with age, classification of disease, SBP, DBP, urinary protein, VEGF, sFlt-1, and IL-4 (P<0.05). Multifactorial logistic regression analysis showed that eclampsia and elevated sFlt-1 were independent risk factors for poor pregnancy outcome in HDP patients, and elevated VEGF and IL-4 were independent protective factors (P<0.05). The area under the curve (AUC) for predicting adverse pregnancy outcomes in HDP patients with serum VEGF, sFlt-1, and IL-4 levels alone and in combination were 0.766, 0.774, 0.770 and 0.905, respectively and the AUC for poor pregnancy outcomes in HDP patients of the combination of VEGF, sFlt-1, and IL-4 predicts was the highest. Conclusion: Decreased serum VEGF and IL-4 levels and increased sFlt-1 levels in HDP patients are associated with HDP classification and poor pregnancy outcome, and the combination of VEGF, sFlt-1, and IL-4 has a high predictive value for poor pregnancy outcome in HDP patients.