母血和脐血炎症指标对组织学绒毛膜羊膜炎的诊断效能

Diagnostic efficacy of inflammatory markers in maternal and umbilical cord blood in histologic chorioamnionitis

目的探讨母血和脐血白细胞介素6（interleukin，IL-6）、C反应蛋白（C-reactiveprotein，CRP）、中性粒细胞与淋巴细胞比值（neutrophil-to-lymphocyte ratio，NLR）和降钙素原（procalcitonin，PCT）等炎症指标在组织学绒毛膜羊膜炎（histologicchorioamnionitis，HCA）中的诊断价值。方法收集2014年1月至2017年7月疑似绒毛膜羊膜炎病例102例为研究对象。根据产后胎盘病理组织学检查，分为HCA组48例和无绒毛膜羊膜炎的对照组（54例）。检测2组母血和脐血血细胞计数，以及IL-6、NLR、CRP和PCT水平。采用t检验、Mann-WhitneyU检验或矿检验（或Fisher精确概率法）对数据进行比较。相关性分析应用Pearson相关分析和偏相关分析，多因素分析采用双变量Logistic回归。对单项指标直接绘制受试者工作特性（receiver operating characteristic，ROC）曲线；联合指标则先以Logistic回归计算相关指标回归方程，再计算对应联合预测概率，然后绘制ROC曲线计算诊断价值。结果（1）HCA组母血IL-6和NLR水平f6．95（2．40～13．50）与3．90（2．30～9．20）pg／ml，z=-5．147；5．03（1．92～9．20）与3．94（1．85～11．17），z=-3．097]，以及脐血白细胞计数、中性粒细胞计数、CRP、IL-6和NLR水平均高于对照组f（9．4±2．0）×10^99／L与（8．6±1．4）×109／L，t=-2．522；（6．87±1．62）×10^9／L与（5．99±1．26）×10^9／L，t=-3．071；12．30（0．50-89．04）与3．18（0．50-88．93）mg／L，z=-4．519；（8．78±2．56）与（4．78±1．45）Pg／ml，t=-7．025；（4．45±1．36）与（3．78±1．22），t=-3．0201（P值均〈0．05）。（2）Logistic回归分析发现，母血IL一6、母血NLR、脐血CRP和脐血IL一6的升高是HCA的独立危险因素[OR（95％CI）分别为1．65（1．32～2．06）、1．34（1．02～1．77）、1．05（1．00～1．11）和2．39（1．72～3．32），P值均〈0．05]。母血IL-6与脐血IL-6、母血NLR与脐血CRP均呈正相关（相关系数分别为0．680和0．230，P值均〈0．05）。（3）单项指标诊断HCA价值方面，脐血IL-6诊断HCA的价值最高，其后依次为母血IL-6、脐血CRP和母血NLR（ROC曲线下面积为0．904、0．796、0．760、0．678）。2项指标联合检测时，“母血NLR＋脐血IL-6”的诊断价值依次高于母血IL-6＋脐血CRP、母血IL-6＋母血NLR，以及母血NLR＋脐血CRP（ROC曲线下面积为0．917、0．870、0．823、0．791）。3项指标联合检测诊断时，“母血IL-6＋母血NLR＋脐血IL-6”这一组合的诊断价值高于“母血IL-6＋母血NLR＋脐血CRP”（ROC曲线下面积为0．919和0．836）。（4）HCA组中，13例（27．1％）发生新生儿并发症；对照组2例（3．7％）发生新生儿并发症（P〈0．05）。结论母血NLR、IL-6，以及脐血NLR、IL-6、CRP水平和脐血白细胞与中性粒细胞计数变化与HCA有关。这些指标中的2项联合检测诊断效能高于各单项指标，而3项联合检测可提高诊断准确性和真实性。

Objective To explore the clinical value of maternal and umbilical blood inflammatory markers, interleukin 6 （IL-6）, neutrophil to-lymphocyte ratio （NLR）, C-reactive protein （CRP） and pro calcitonin （PCT）, in the diagnosis of histologic chorioamnionitis （HCA）. Methods A total of 102 suspected ehorioamnionitic cases were enrolled from January 2014 to July 2017. They were assigned into two groups based upon postpartum histopathological examination of placenta： HCA group （48 eases） and control group （54 cases）. Maternal and umbilical blood samples were collected for routine blood test and tested for IL 6, NLR, CRP and PCT levels. T, Mann-Whitney U or Chi-square （or Fisher＇s exact） test was used for data comparison. Meaningful indicators in maternal and umbilical cord blood were analyzed by logistic regression analysis and correlation analysis. At the same time, receiver operating characteristic （ROC） curve was drawn to evaluate their diagnostic values. Results （1） IL-6 level and NLR in maternal blood in HCA group were higher than those in control group [6.95 （2.40-13.50） vs 3.90 （2.30 9.20） pg/ml, Z= - 5.147; 5.03 （1.92-9.20） vs 3.94 （1.85- 11.17）, Z= - 3.097; both P〈0.05], and the levels of white blood cells, neutrophile granulocytes, CRP and IL-6 as well as NLR in umbilical cord blood were also higher [（9.4 ± 2.0）×10^9/L vs （8.6 ±1.4）×10^9/L, t= - 2.522; （6.87 ±1.62）×10^9/L vs （5.99±1.26）×10^9/L, t= - 3.071; 12.30 （0.50 89.04） vs 3.18 （0.50-88.93） mg/L, Z= - 4.519; （8.78±2.56） vs （4.78±1.45） pg/ml, t= - 7.025; （4.45±1.36） vs （3.78±1.22）, t= - 3.020; all P〈0.05]. （2） Logistic regression analysis showed that elevated levels of IL 6 and NLR in maternal blood and CRP and IL-6 in umbilical cord blood were independent risk factors for HCA [OR （95%C/）： 1.65 （1.32-2.06）, 1.34 （1.02-1.77）, 1.05 （1.00-1.11） and 2.39 （1.72-3.32）, all P〈0.05]. Positive correlations were found between the levels of IL 6 in maternal and umbilical cord blood, and between NLR in maternal blood and CRP level in umbilical cord blood （correlation coefficient： 0.680 and 0.230, both P〈0.05）. （3） IL-6 level in umbilical blood was of the greatest value in the diagnosis of HCA among all single markers, followed by IL-6 in maternal blood, CRP in umbilical blood and NLR in maternal blood [area under the ROC curve （AUC）： 0.904, 0.796, 0.760 and 0.678]. When two indexes were combined, NLR in maternal blood＋IL-6 in umbilical cord blood showed the highest diagnostic value, followed by, IL-6 in maternal blood＋CRP in umbilical cord blood, IL-6＋NLR in maternal blood and NLR in maternal blood＋CRP in umbilical cord blood （AUC： 0.917, 0.870, 0.823 and 0.791）. When three indexes was used in combination, the diagnostic value of IL-6 in maternal and umbilical cord blood＋NLR in maternal blood was higher than that of IL-6 and NLR in maternal blood＋CRP in umbilical cord blood （AUC： 0.919 and 0.836）. （4） There were 13 cases （27.1%） with neonatal complications in HCA group and two （3.7%） in control group （P〈0.05）. Conclusions Changes in NLR and IL-6 levels in maternal blood and NLR, IL-6 and CRP levels, and white blood cells and neutrophile granulocytes counts in umbilical cord blood are associated with HCA. The diagnostic efficacy of two indexes combined is superior to that of single index, while the combination of three indexes can significantly improve the diagnostic accuracy and authenticity.