血清肠脂肪酸结合蛋白质在新生儿坏死性小肠结肠炎诊治中的临床探讨

Clinical study of serum intestinal fatty acid-binding protein level in diagnosis and treatment of neonatal necrotizing enterocolitis

目的探究血清肠脂肪酸结合蛋白质(intestinaI fatty acid-binding protein,IFABP)在新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis,NEC)临床诊治中的应用价值。方法采用病例对照研究方法,以2018年5月至2019年12月福建省妇幼保健院新生儿科收治的早产NEC患儿40例为病例组,按照1∶1匹配方法,选取在性别、胎龄、出生体重与病例组相近的同期住院非NEC早产患儿40例作为对照组。根据修正Bell分期标准,将病例组进一步细分为NECⅠ期组、Ⅱ期组及NECⅢ期组,对病例组发病24h及经积极治疗后发病72h采集2次血液标本;对照组在病例组第1次采血相近日龄采血1次,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测各组血清I-FABP水平,比较两次采血各组I-FABP水平差异。结果共收治病例组:NECⅠ期组19例,NECⅡ期组11例,NECⅢ期组10例。NECⅠ期组、NECⅡ期组及Ⅲ期组发病24h血清I-FABP水平分别为3.296(1.927,3.599)ng/ml、16.093(13.117,24.094)ng/ml和23.595(18.665,25.868)ng/ml,均高于对照组1.485(0.962,2.459)ng/ml,差异均有统计学意义(Z对照组-NEC I期组=﹣3.244,P<0.05;Z对照组-NECⅡ期组=﹣5.038,P<0.05;Z对照组-NECⅢ期组=﹣4.851,P<0.05)。血清I-FABP水平与NEC临床分期的Spearman等级相关系数为0.817,P<0.05。经积极治疗后发病72h血清I-FABP水平在NECⅠ期组和NECⅡ+Ⅲ期组[分别为0.952(0.723,1.025)ng/ml和1.049(0.962,3.353)ng/ml]均较发病24h[分别为3.296(1.927,3.599)ng/ml、16.998(13.171,22.495)ng/ml]明显下降,差异均有统计学意义(ZNEC I期组治疗前-NEC I期组治疗后=﹣4.832,P<0.05;ZNECⅡ+Ⅲ期组治疗前-NECⅡ+Ⅲ期组治疗后=﹣4.333,P<0.05)。受试者工作特征曲线分析I-FABP诊断NEC的最佳界值为2.953ng/ml,灵敏度82.5%,特异度85.0%,对判断重度NEC的最佳界值为16.488g/ml,灵敏度100%,特异度91.4%。结论I-FABP可能成为NEC早期诊断,尤其是病情严重程度判断的临床指标之一,对疾病监测及肠道恢复判断具有一定的临床参考价值。

Objective To explore the value of serum intestinal fatty acid-binding protein(I-FABP)in necrotizing enterocolitis(NEC).Methods We conducted a case-control study on preterm infants with stageⅠtoⅢNEC,and compared them with 1:1 matched(gender,gestational age and birth weight)controls tested negative for NEC.They were admitted to the neonatal department of Fujian Maternity and Child Health Hospital from May 2018 to December 2019.Blood samples were collected twice at 24h and 72h after the onset of the disease in the case group;the blood was collected in control group at approximately the same age as it was firstly collected in the case group.Enzyme-linked immunosorbent assay(ELISA)was used for the detection and measurement of the included neonates’I-FABP in serum.Results A total of 40 cases were treated in the study period,including 19 cases in NEC stageⅠ,11 cases in NEC stageⅡ,and 10 cases in NEC stageⅢ.There were significantly higher median levels of serum I-FABP at 24h after the onset of NEC among patients in NEC stageⅠ,ⅡandⅢ[3.296(1.927,3.599),16.093(13.117,24.049)ng/ml,and 23.595(18.655,25.868)ng/ml,respectively]compared with control group[1.485(0.962,2.459)ng/ml]with P˂0.05 for all[Zcontrol-NECⅠgroup=﹣3.244,P˂0.05;Zcontrol-NECⅡgroup=﹣5.038,P˂0.05;Zcontrol-NECⅢgroup=﹣4.851,P˂0.05].The Spearman’s rank correlation coefficient between serum I-FABP concentration and NEC clinical stage was 0.817(P˂0.05).The median value of serum I-FABP of NEC stageⅠ,ⅡandⅢcases at 72h after the onset of NEC[0.952(0.723,1.025)ng/ml,1.049(0.962,3.353)ng/ml,respectively]were significantly lower after treatment than those at 24h after the onset of the disease[3.296(1.927,3.599)ng/ml and 16.998(13.171,22.495)ng/ml]with P˂0.05 for all(ZNECⅠfor 24h-NECⅠfor 72h=﹣4.832,P˂0.05;ZNECⅡ+Ⅲfor 24h-NECⅡ+Ⅲfor 72h=﹣4.333,P˂0.05).Cut-off values for predicting NEC were estimated to be 2.953 ng/ml with 82.5%sensitivity and 85.0%specificity.Cut-off values in discriminating severe NEC from mild NEC were 16.488ng/ml with 100%sensitivity and 91.4%specificity.Conclusion Serum I-FABP may become one of the clinical indicators for early diagnosis of NEC,especially the severity of the disease.It has certain clinical reference value for disease monitoring and intestinal recovery.