新生儿脐血浆多种细胞因子水平检测与早发型新生儿败血症的相关性研究

Correlation between the Detection of Multiple Cytokine Levels in Neonatal Umbilical Cord Plasma and Early-onset Neonatal Sepsis

目的分析新生儿脐带血血浆多种细胞因子表达水平与早发型新生儿败血症(early-onset neonatal sepsis,EONS)的相关性,旨在筛选出对新生儿早发型败血症有较大诊断价值的细胞因子。方法以2021年9月~2023年6月在延安市人民医院出生的足月新生儿和早产新生儿(胎龄均≥32周)310例作为受试对象,根据临床体征、实验室检查和血培养结果分为三组:无败血症基础对照组、新生儿早发型败血症血培养阳性组和新生儿早发型败血症血培养阴性组;在受试对象出生后立即采集脐带血,测定血浆细胞因子IL-2,IL-4,IL-6,IL-9,IL-10,IL-21,IFN-γ和TNF-α的表达水平,筛选出表达水平较高(关联性较高)的细胞因子,用受试者工作特征(receiver operating characteristic,ROC)曲线分析其单独检测和联合检测对新生儿早发型败血症诊断的特异度和敏感度。结果患儿脐血浆上述8种细胞因子中,IL-6,IL-9和IL-21浓度在新生儿早发型败血症血培养阳性组(392.6±258.7 pg/ml,11.9±7.5 pg/ml,29.1±16.8 pg/ml)和新生儿早发型败血症血培养阴性组(353.8±244.5 pg/ml,10.4±6.3 pg/ml,27.7±19.2 pg/ml)显著高于无败血症基础对照组(34.9±25.1 pg/ml,5.9±4.5 pg/ml,10.8±10.1 pg/ml),差异具有统计学意义(t=23.961,20.732;15.174,17.824;22.466,21.193,均P<0.05),其中IL-6浓度升高最为明显。新生儿早发型败血症血培养阳性组与新生儿早发型败血症血培养阴性组的细胞因子表达水平差异无统计学意义(t=0.276~3.377,均P>0.05)。ROC曲线分析,IL-6,IL-9,IL-21截断值分别为123.0 pg/ml,3.60 pg/ml和6.00 pg/ml,IL-6,IL-9和IL-21单独检测ROC曲线下面积分别为0.876(95%CI:0.786~0.955),0.782(95%CI:0.667~0.875)和0.825(95%CI:0.737~0.913),三种细胞因子联合检测,ROC曲线下面积为0.930(95%CI:0.875~0.997),IL-6,IL-9和IL-21联合检测能显著地提高检测的特异度和敏感度,差异具有统计学意义(Z=2.137,2.391,2.257,均P<0.05)。新生儿早发型败血症血培养阳性组与新生儿早发型败血症血培养阴性组的细胞因子表达水平差异均无统计学意义(t=0.276~3.377,均P>0.05)。结论新生儿早发型败血症患儿脐血浆细胞因子IL-6,IL-9和IL-21显著升高,联合检测IL-6,IL-9和IL-21对新生儿早发型败血症有较好的诊断价值。

Objective To investigate correlation between the expression level of multiple cytokine levels in neonatal umbilical cord plasma and early-onset sepsis for screening out the cytokines with good diagnostic value for early-onset neonatal sepsis(EONS).Methods Full-term neonates and preterm neonates(Gestational age≥32 weeks)of 310 cases between September 2021 and June 2023 were selected as study subjects.According to clinical signs,laboratory results and blood culture,these subjects were divided into 3 groups:control group without sepsis,EONS blood culture positive group and EONS blood culture negative group.Umbilical cord blood plasma of all subjects was collected within 72 hours after birth.The expression levels of cytokines IL-2,IL-4,IL-6,IL-9,IL-10,IL-21,IFN-γand TNF-αwere determined,and cytokines with high expression levels(high correlation)were screened out.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the selected cytokines in the diagnosis of neonatal early-onset sepsis.Results Among the 8 cytokines mentioned above,the concentrations of IL-6,IL-9 and IL-21 in cord blood plasma of neonatal early-onset sepsis positive blood culture patients(392.6±258.7pg/ml,11.9±7.5pg/ml,29.1±16.8 pg/ml)and negative blood culture patients(353.8±244.5pg/ml,10.4±6.3pg/ml,27.7±19.2pg/ml)were higher than those of the control group(34.9±25.1pg/ml,5.9±4.5pg/ml,10.8±10.1pg/ml),with significant differences(t=23.961,20.732;15.174,17.824;22.466,21.193,all P<0.01),and the increase of IL-6 concentration was the most obvious.ROC curve analysis(the cut-off values of IL-6,IL-9 and IL-21:123.0 pg/ml,3.60 pg/ml,6.00 pg/ml,respectively)showed that the areas under the ROC curve for IL-6,IL-9 and IL-21 alone detection were 0.876(95%CI:0.786~0.955),0.782(95%CI:0.667~0.875)and 0.825(95%CI:0.737~0.913),respectively.The area under the ROC curve for the combined detection of IL-6,IL-9 and IL-21 was 0.930(95%CI:0.875~0.997).The combined detection of IL-6,IL-9 and IL-21 improved the specificity and sensitivity of the test than IL-6,IL-9 and IL-21 alone detection,and the differences were statistically significant(Z=2.137,2.391,2.257,all P<0.05).There was no significant difference in cytokine expression between positive blood culture and negative blood culture neonates with early-onset sepsis(t=0.276~3.377,all P>0.05).Conclusion The cytokines expression of IL-6,IL-9 and IL-21 in neonatal umbilical cord plasma of neonatal early-onset sepsis were increased.Combined detection of IL-6,IL-9 and IL-21 has good diagnostic value for early-onset neonatal sepsis.