B族链球菌孕妇感染血清炎症因子、Th1/Th2、β-hCG的变化及其对胎膜早破、妊娠结局的预测价值

Changes of serum inflammatory factors, Th1/Th2, and β-hCG in pregnant women with GBS infection and their predictive value in occurrence of PROM and pregnancy outcome

摘要:

目的 探讨B族链球菌孕妇感染血清炎症因子、Th1/Th2、β-绒毛膜促性腺激素（β-hCG）变化及对胎膜早破发生、妊娠结局的预测价值。方法 选取2016年3月—2019年1月攀枝花市妇幼保健院收治的168例B族链球菌感染孕妇（GBS感染组）及200例无B族链球菌感染孕妇（无GBS感染组）。根据是否发生胎膜早破将B族链球菌感染组孕妇分为无胎膜早破组147例、胎膜早破组21例，比较B族链球菌感染与未感染者、胎膜早破与无胎膜早破者血清炎症因子、Th1/Th2细胞因子［干扰素-γ（IFN-γ）、IL-2、IL-4、IL-10］、β-hCG水平、胎膜早破发生率、妊娠结局、新生儿Apgar评分。采用Logistic回归性分析影响胎膜早破发生的因素，采用受试者工作特征（ROC）曲线及ROC下面积（AUC）分析各指标预测胎膜早破发生的价值，采用Pearson法分析各指标与新生儿Apgar评分的相关性。结果 B族链球菌感染者IL-1、TNF-α、IFN-γ、IL-2、β-hCG水平及胎膜早破发生率、不良妊娠结局发生率较无B族链球菌感染者高，IL-4、IL-10水平较无B族链球菌感染者低（P <0.05）；胎膜早破组患者IL-1、TNF-α、IFN-γ、IL-2、β-hCG水平较无胎膜早破组患者高，IL-4、IL-10水平及新生儿Apgar评分较无胎膜早破组患者低（P <0.05）；高IL-1水平［O^R=3.161（95% CI：2.551，3.916）］、TNF-α水平［O^R=1.985（95% CI：1.367，2.883）］、IFN-γ水平［O^R=1.526（95% CI：1.269，1.834）］、IL-2水平［O^R=1.809（95% CI：1.112，2.943）］及β-hCG水平［O^R=2.944（95% CI：1.819，4.765）］是胎膜早破发生的危险因素（P <0.05），高IL-4水平［O^R=0.397（95% CI：0.204，0.771）］与IL-10水平［O^R=0.545（95% CI：0.531，0.559）］是胎膜早破的保护因素（P <0.05）；预测胎膜早破的AUC IFN-γ> IL-2 >β-hCG> IL-4 > IL-1 > TNF-α > IL-10，截断值依次为>12.99 ng/ml（敏感性为61.90%，特异性为82.31%）、> 10.6 ng/ml（敏感性为85.71%，特异性为55.10%）、>13 280.64 IU/L（敏感性为90.48%，特异性为46.26%）、< 2.12 ng/ml（敏感性为71.43%，特异性为62.59%）、>0.4 ng/ml（敏感性为66.67%，特异性为69.39%）、>435.56 pg/ml（敏感性为95.24%，特异性为31.97%）、<2.12 ng/ml（敏感性为47.62%，特异性为73.47%）；IL-1、TNF-α、IFN-γ、IL-2、β-hCG水平与新生儿Apgar评分呈负相关，IL-4、IL-10水平与新生儿Apgar评分呈正相关（P <0.05）。结论 B族链球菌感染孕妇血清IL-1、TNF-α炎症因子与β-hCG水平较高，Th1/Th2失衡，检测外周血各指标水平，可预测胎膜早破的发生及妊娠结局。

Abstract:

Objective To explore the changes of serum inflammatory factors, Th1/Th2, and β-chorionic gonadotropin (β-hCG) in pregnant women with group B streptococcus (GBS) infection and their predictive value for the occurrence of premature rupture of membranes (PROM) and pregnancy outcomes.Methods A total of 168 pregnant women with GBS infection and 200 pregnant women without GBS infection who were admitted to our hospital from March 2016 to January 2019 were selected. According to whether PROM occurred, pregnant women with GBS infection were divided into non-PROM group (n = 147) and PROM group (n = 21). The serum inflammatory factors and Th1/Th2 cytokines [interferon-γ (IFN-γ), IL-2, IL-4, IL-10], β-hCG levels, incidence of PROM, pregnancy outcomes, and neonatal Apgar score of patients with and without GBS infection and PROM were compared. Logistic regression analysis was used to analyze the factors affecting the occurrence of PROM; receiver operating characteristic (ROC) curve and area under ROC (AUC) were used to analyze the value of PROM; and Pearson was used to analyze the correlation between each index and the Apgar score of the newborn.Results The levels of IL-1, TNF-α, IFN-γ, IL-2, β-hCG, and the incidences of PROM and adverse pregnancy outcomes were higher in GBS infected persons than in those without GBS infection (P < 0.05). The levels of IL-4 and IL-10 were lower than in those without GBS infection (P < 0.05). The levels of IL-1, TNF-α, IFN-γ, IL-2, and β-hCG were higher in PROM patients than in patients without PROM (P < 0.05). The levels of IL-4 and IL-10, and Apgar scores of neonates were lower than those of patients without PROM (P < 0.05). High IL-1 level [O^R = 3.161 (95% CI: 2.551, 3.916)] and TNF-α level [O^R = 1.985 (95% CI: 1.367, 2.883)], IFN-γ level [O^R = 1.526 (95% CI: 1.269, 1.834)], IL-2 level [O^R = 1.809 (95% CI: 1.112, 2.943)], and β-hCG level [O^R= 2.944 (95% CI: 1.819, 4.765)] were risk factors for PROM, and high IL-4 level [O^R = 0.397, (95% CI: 0.204, 0.771)] and IL-10 level [O^R = 0.545 (95% CI: 0.531, 0.559) ]were protective factors for PROM (P < 0.05). The predicted AUC of PROM was IFN-γ > IL-2 > β-hCG> IL-4> IL-1> TNF-α> IL-10, and the cut-off value were > 12.99 ng/ml (sensitivity was 61.90%, specificity was 82.31%), > 10.6 ng/ml (sensitivity was 85.71%, specificity was 55.10%), >13 280.64 IU/L (sensitivity was 90.48%, specificity was 46.26%), < 2.12 ng/ml (sensitivity was 71.43%, specificity was 62.59%), > 0.4 ng/ml (sensitivity was 66.67%, specificity was 69.39%), >435.56 pg/ml (sensitivity was 95.24%, specificity was 31.97%), < 2.12 ng/ml (sensitivity was 47.62%, specificity was 73.47%), respectively. The levels of IL-1, TNF-α, IFN-γ, IL-2, and β-hCG were negatively correlated with the Apgar scores of newborns, and the levels of IL-4 and IL-10 were positively correlated with Apgar scores of newborns (P < 0.05).Conclusion High levels of serum IL-1, TNF-α inflammatory factors, β-hCG, as well as Th1/Th2 imbalance, appear in GBS-infected pregnant women, and the detection of peripheral blood index levels can predict the occurrence of PROM and pregnancy outcome.