Abstract:

Objective　To explore the effect of Th1/Th2 cell balance on fetal intrauterine distress in patients with intrahepatic cholestasis of pregnancy (ICP), and provide reference for clinical prevention of fetal intrauterine distress. Methods　A total of 96 ICP patients admitted to Xi'an People's Hospital from January 2023 to January 2024 were selected as the case group, including 62 primiparas and 34 multiparas, aged (28.46±4.20) years, with a gestational age of (33.70±2.34) weeks. Another 96 healthy pregnant women during the same period were selected as the control group, including 66 primiparas and 30 multiparas, aged (27.60±4.12) years, with a gestational age of (32.85±2.42) weeks. The case group was subdivided into an occurrence group and a non-occurrence group based on whether fetal intrauterine distress had occurred. The levels of Th1 cytokines [tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] and Th2 cytokine [interleukin (IL) -4] were detected by enzyme-linked immunosorbent assay (ELISA), and IFN-γ/IL-4 and TNF-α/IL-4 were calculated. The differences in TNF-α, IFN-γ, IL-4, IFN-γ/IL-4, and TNF-α/IL-4 were compared between the case group and the control group, as well as between the occurrence group and the non-occurrence group. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of fetal intrauterine distress in ICP patients. The receiver operating characteristic curve (ROC) was drawn to analyze the predictive value of Th1/Th2 cytokines for fetal intrauterine distress in ICP patients. Independent sample t test and χ² test were used. Results　The levels of TNF-α, IFN-γ, IFN-γ/IL-4, and TNF-α/IL-4 in the case group were higher than those in the control group [(102.31±18.33) ng/L vs. (64.20±12.62) ng/L, (166.78±32.33) ng/L vs. (138.39±28.10) ng/L, (3.36±0.22) vs. (1.15±0.12), (2.06±0.12) vs. (0.53±0.08)], but the level of IL-4 was lower than that in the control group [(49.57±16.32) ng/L vs. (120.54±20.36) ng/L], with statistically significant differences (t=16.779, 6.494, 86.407, 103.943, and 26.649, all P<0.001). Among the 96 ICP patients, 22 cases (22.92%) experienced fetal intrauterine distress, including 8 cases of acute fetal distress and 14 cases of chronic fetal distress. The levels of total serum bile acids, total serum bilirubin, TNF-α, IFN-γ, IFN-γ/IL-4, and TNF-α/IL-4 in the occurrence group were higher than those in the non-occurrence group, but the level of IL-4 was lower than that in the non-occurrence group, with statistically significant differences (all P<0.05). Multivariate logistic regression analysis showed that total serum bile acids, TNF-α, IFN-γ, IL-4, IFN-γ/IL-4, and TNF-α/IL-4 were independent influencing factors for the occurrence of fetal distress in ICP patients (all P<0.05). The ROC curve was drawn, it was found that the areas under the curves (AUCs) of TNF-α, IFN-γ, and IL-4 in predicting fetal distress in ICP patients were all >0.70, and the AUCs of IFN-γ/IL-4 and TNF-α/IL-4 in predicting fetal distress were both >0.85. Conclusion　The shift of Th1/Th2 balance towards Th1 in ICP patients affects the risk of fetal intrauterine distress, and detecting IFN-γ/IL-4 and TNF-α/IL-4 helps to predict fetal intrauterine distress.

Key words:

Intrahepatic cholestasis of pregnancy, Fetal intrauterine distress, Th1 cytokines, Th2 cytokines

摘要：

目的　探讨辅助性T细胞（Th）1/Th2细胞平衡状态对妊娠期肝内胆汁淤积症（ICP）患者胎儿窘迫的影响，为临床预防胎儿窘迫提供参考依据。方法　选择2023年1月至2024年1月西安市人民医院收治的96例ICP患者作为病例组，其中初产妇62例、经产妇34例，年龄（28.46±4.20）岁，孕周（33.70±2.34）周。另选取同期健康体检孕妇96例作为对照组，其中初产妇66例、经产妇30例，年龄（27.60±4.12）岁，孕周（32.85±2.42）周。病例组依据是否发生胎儿窘迫分为发生组和未发生组。采用酶联免疫吸附试验检测Th1型细胞因子肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和Th2型细胞因子白细胞介素（IL）-4水平，并计算IFN-γ/IL-4和TNF-α/IL-4。比较病例组和对照组、发生组与未发生组之间的TNF-α、IFN-γ、IL-4、IFN-γ/IL-4和TNF-α/IL-4差异；采用单因素和多因素logistic回归分析ICP患者发生胎儿窘迫的影响因素；绘制受试者操作特征曲线（ROC）分析Th1/Th2细胞因子对ICP患者发生胎儿窘迫的预测价值。采用独立样本t检验、χ²检验。结果　病例组TNF-α、IFN-γ、IFN-γ/IL-4、TNF-α/IL-4均高于对照组［（102.31±18.33）ng/L比（64.20±12.62）ng/L、（166.78±32.33）ng/L比（138.39±28.10）ng/L、（3.36±0.22）比（1.15±0.12）、（2.06±0.12）比（0.53±0.08）］，IL-4低于对照组［（49.57±16.32）ng/L比（120.54±20.36）ng/L］，差异均有统计学意义（t=16.779、6.494、86.407、103.943、26.649，均P<0.001）。96例ICP患者中发生胎儿窘迫22例（22.92%），其中急性胎儿窘迫8例、慢性胎儿窘迫14例。发生组血清总胆汁酸、血清总胆红素、TNF-α、IFN-γ、IFN-γ/IL-4、TNF-α/IL-4均高于未发生组，IL-4低于未发生组，差异均有统计学意义（均P<0.05）。多因素logistic回归分析显示，血清总胆汁酸、TNF-α、IFN-γ、IL-4、IFN-γ/IL-4、TNF-α/IL-4均是ICP患者发生胎儿窘迫的独立影响因素（均P<0.05）。绘制ROC发现，TNF-α、IFN-γ、IL-4预测ICP患者发生胎儿窘迫的曲线下面积（AUC）均>0.70，IFN-γ/IL-4、TNF-α/IL-4预测胎儿窘迫的AUC均>0.85。结论　ICP患者Th1/Th2平衡向Th1偏移，增加ICP患者胎儿窘迫的发生风险，且检测IFN-γ/IL-4、TNF-α/IL-4有助于预测胎儿窘迫。

关键词:

妊娠期肝内胆汁淤积症, 胎儿窘迫, Th1细胞因子, Th2细胞因子