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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (04) : 433 -441. doi: 10.3877/cma.j.issn.1673-5250.2022.04.009

论著

腹部超声联合白细胞介素-6检测对新生儿坏死性小肠结肠炎的诊断及预后评估价值
郭建康1,†(), 柏艳红1, 梁优1, 余果1, 范志刚2   
  1. 1三二〇一医院超声医学科，汉中　723000
    2三二〇一医院肿瘤内一科，汉中　723000
  • 收稿日期:2021-12-30 修回日期:2022-06-21 出版日期:2022-08-01
  • 通信作者: 郭建康

Diagnostic and prognostic evaluation values of abdominal ultrasound combined with interleukin-6 detection in neonatal necrotizing enterocolitis

Jiankang Guo1,†(), Yanhong Bai1, You Liang1, Guo Yu1, Zhigang Fan2   

  1. 1Department of Ultrasound Medicine, 3201 Hospital, Hanzhong 723000, Shaanxi Province, China
    2Department of Oncology, 3201 Hospital, Hanzhong 723000, Shaanxi Province, China
  • Received:2021-12-30 Revised:2022-06-21 Published:2022-08-01
  • Corresponding author: Jiankang Guo
  • Supported by:
    Key R&D Program of Shaanxi Province(2021SF-044)
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引用本文：

郭建康, 柏艳红, 梁优, 余果, 范志刚. 腹部超声联合白细胞介素-6检测对新生儿坏死性小肠结肠炎的诊断及预后评估价值[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(04): 433-441.

Jiankang Guo, Yanhong Bai, You Liang, Guo Yu, Zhigang Fan. Diagnostic and prognostic evaluation values of abdominal ultrasound combined with interleukin-6 detection in neonatal necrotizing enterocolitis[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(04): 433-441.

目的

探讨腹部超声联合血清白细胞介素(IL)-6水平检测，对新生儿坏死性小肠结肠炎(NEC)的诊断及预后评估价值。

方法

选择2018年3月至2020年3月，于三二〇一医院新生儿重症监护病房(NICU)收治的138例NEC新生儿为研究对象，并纳入NEC组；将同期在该院出生并收入NICU的65例非NEC新生儿纳入非NEC组。根据Bell-NEC分级标准，将NEC组新生儿进一步分为疑似亚组(n＝79)和确诊亚组(n＝59)；根据治疗方法，将NEC组新生儿进一步分为内科治疗亚组(n＝94)和手术亚组(n＝44)。回顾性分析NEC组和非NEC组新生儿临床病例资料。采用χ2检验及独立样本t检验，对这些新生儿临床资料，包括入院时血清IL-6水平，以及NEC 2个亚组腹部超声辅助诊断NEC指标、血清IL-6水平等，进行统计学比较；采用多因素非条件logistic回归分析方法，分析影响NEC发生的独立危险因素；采用受试者工作特征(ROC)曲线，评估腹部超声、血清IL-6水平检测及二者联合检测，对NEC的诊断价值；根据ROC曲线的血清IL-6水平临界值和NEC内科治疗亚组与手术亚组新生儿比较中，差异有统计学意义的5项腹部超声检测指标，将NEC组新生儿分为A亚组(n＝18，血清IL-6>6.25 ng/mL＋5项超声检测指标均呈阳性)，B亚组(n＝25，血清IL-6≤6.25 ng/mL＋5项超声检测指标均呈阴性)和C亚组(n＝95，除A、B亚组之外的其余NEC新生儿)，采用Kaplan-Meier生存曲线分析，比较A、B、C亚组患儿的1年生存率。本研究经三二〇一医院医学伦理委员会审批(审批文号：〔2022〕004)。所有受试儿监护人对研究知情同意，并签署临床研究知情同意书。

结果

①NEC组早产儿比例，羊水胎粪污染及新生儿脓毒症发生率，入院时血清IL-6水平，母亲妊娠期糖尿病、胎膜早破及感染发生率，以及开奶时间，均高于或长于非NEC组，而母乳喂养率及预防性益生菌使用率，则均低于非NEC组，并且上述差异均有统计学意义(P<0.05)。②多因素非条件logistic回归分析：早产(OR＝2.624，95%CI：1.269~3.451，P＝0.035)，羊水胎粪污染(OR＝1.847，95%CI：1.358~2.634，P＝0.028)，新生儿脓毒症(OR＝4.006，95%CI：3.039~5.138，P＝0.022)，母亲妊娠期糖尿病(OR＝1.653，95%CI：1.142~2.869，P＝0.012)，非单纯母乳喂养(OR＝1.480，95%CI：1.028~2.366，P＝0.006)，未预防性使用益生菌(OR＝3.318，95%CI：1.235~3.959，P<0.001)，血清IL-6>6.25 ng/mL(OR＝2.314，95%CI：1.497~4.247，P＝0.018)，均为影响NEC发生的独立危险因素。③NEC确诊亚组患儿肠壁增厚、门静脉积气、肠管扩张、肠管充气减少、肠道蠕动消失、腹腔积液(透声差)、肠壁血流灌注减少腹部超声检出率，均高于NEC疑似亚组，并且差异均有统计学意义(P<0.05)。④ROC曲线分析显示，腹部超声联合血清IL-6水平诊断NEC的ROC曲线下面积(AUC)为0.854(95%CI：0.781~0.927，P<0.001)。二者联合检测诊断NEC的ROC-AUC、敏感度、特异度、阳性预测值及阴性预测值，均分别高于腹部超声、血清IL-6水平检测，并且差异均有统计学意义(P<0.05)。⑤NEC手术亚组肠壁增厚、肠管扩张、肠管充气减少、肠道蠕动消失及腹腔积液(透声差)腹部超声检出率，以及入院时血清IL-6水平，均显著高于内科治疗亚组，并且差异均有统计学意义(P<0.05)。⑥B亚组患儿1年生存率为88.0%，分别高于A亚组(55.6%)和C亚组(69.5%)，并且差异均有统计学意义(P<0.05)。

结论

腹部超声联合血清IL-6水平检测，可提高NEC诊断率，并且对患儿预后有较好预测价值。

关键词: 超声检查, 白细胞介素6, 小肠结肠炎，坏死性, 诊断, 预后, 婴儿，新生
Objective

To investigate diagnostic and prognostic evaluation values of abdominal ultrasonography combined with serum interleukin(IL)-6 level in neonatal necrotizing enterocolitis (NEC).

Methods

A total of 138 neonates with NEC treated in neonatal intensive care unit (NICU) of 3201 Hospital from March 2018 to March 2020 were enrolled into NEC group, and 65 newborns born in the same hospital and treated in NICU also during the same period were selected into non-NEC group. According to Bell-NEC grading standard, neonates in NEC group were furtherly divided into suspected subgroup (n=79) and diagnosed subgroup (n=59). According to treatment methods, neonates in NEC group were furtherly divided into medical treatment subgroup (n=94) and operation subgroup (n=44). The clinical data of neonates in two groups were retrospectively analyzed. Clinical data (including serum IL-6 level at admission) of neonates between NEC group and non-NEC group, also abdominal ultrasonography diagnostic indexes of NEC and serum IL-6 level of neonates between NEC subgroups were statistically compared by chi-square test and independent-samples t test. Independent risk factors of NEC in neonates were analyzed by multivariate non-conditional logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of abdominal ultrasonography, serum IL-6 level and their combination for NEC. According to critical value of serum IL-6 level of ROC curve and five abdominal ultrasonography indexes with statistically significant differences between NEC medical treatment subgroup and operation subgroup, neonates in NEC group were divided into subgroup A (n=18, serum IL-6>6.25 ng/mL + with all of positive five ultrasonography indexes), and subgroup B (n=25, serum IL-6≤6.25 ng/mL + with all of negative five ultrasonography indexes), and subgroup C (n=95, other NEC neonates except subgroup A and B). Kaplan-Meier survival curve analysis was used to compare the 1-year survival rates of subgroups A, B and C. This study was approved by the Medical Ethics Committee of 3201 Hospital (Approval No.[2022]004). All guardians of subjects gave informed consent to the study and signed informed consents for clinical study.

Results

① The proportion of premature infants, incidence of amniotic fluid meconium contamination and neonatal sepsis, serum IL-6 level at admission, incidence of maternal gestational diabetes, premature rupture of membranes and infection, and starting time of breast-feeding in NEC group were higher or longer than those in non-NEC group, while breast-feeding rate and utilization rate of probiotics were lower than those in non-NEC group, and all the differences were statistically significant (P<0.05). ② Multivariate logistic regression analysis showed that preterm birth (OR=2.624, 95%CI: 1.269-3.451, P=0.035), amniotic fluid meconium contamination (OR=1.847, 95%CI: 1.358-2.634, P=0.028), neonatal sepsis (OR=4.006, 95%CI: 3.039-5.138, P=0.022), maternal gestational diabetes mellitus (OR=1.653, 95%CI: 1.142-2.869, P=0.012), non-exclusive breastfeeding (OR=1.480, 95%CI: 1.028-2.366, P=0.006), no probiotics prophylaxis (OR=3.318, 95%CI: 1.235-3.959, P<0.001) and serum IL-6>6.25 ng/mL (OR=2.314, 95%CI: 1.497-4.247, P=0.018) were all independent risk factors of NEC in neonates. ③ Abdominal ultrasonography detection rates of intestinal wall thickening, portal venous air accumulation, intestinal dilatation, reduced intestinal inflation, intestinal peristalsis disappearance, peritoneal effusion (poor ultrasound transmission) and reduced intestinal wall blood perfusion in NEC diagnosed subgroup were higher than those in NEC suspected subgroup, and the differences were statistically significant (P<0.05). ④ ROC curve analysis showed that the area under curve (AUC) of ROC of abdominal ultrasonography combined with serum IL-6 level in diagnosis of NEC was 0.854 (95%CI: 0.781-0.927, P<0.001). The ROC-AUC, sensitivity, specificity, positive predictive value and negative predictive value of their combination for diagnosis of NEC were higher than those of abdominal ultrasonography and serum IL-6 level, respectively, and the differences were statistically significant (P<0.05). ⑤ Abdominal ultrasonography detection rates of intestinal wall thickening, intestinal dilation, reduced intestinal inflation, intestinal peristalsis disappearance and peritoneal effusion (poor ultrasound transmission), and serum IL-6 level at admission in NEC operation subgroup were significantly higher than those in NEC medical treatment subgroup, and the differences were statistically significant (P<0.05). ⑥ The 1-year survival rate of subgroup B was 88.0%, which was higher than that of subgroup A (55.6%) and subgroup C (69.5%), respectively, and the differences were statistically significant (P<0.05).

Conclusion

Abdominal ultrasonography combined with serum IL-6 level can improve diagnostic rate of neonatal NEC, and has good prognostic evaluation values for NEC children.

Key words: Ultrasonography, Interleukin-6, Enterocolitis, necrotizing, Diagnosis, Prognosis, Infant, newborn
表1 NEC组和非NEC组新生儿临床资料比较
组别 例数 发病日龄(d，±s) 男性[例数(%)] 出生胎龄(周，±s) 出生体重(kg，±s) 分娩方式[例数(%)] 生后1 min Apgar评分(分，±s)
剖宫产 自然分娩
NEC组 138 13.5±7.0 80(58.0) 34.9±5.0 1.9±0.7 35(25.4) 103(74.6) 8.0±1.5
非NEC组 65 12.9±6.4 36(55.4) 35.4±5.2 1.8±0.7 12(18.5) 53(81.5) 7.6±1.5
统计量   t＝0.585 χ2＝0.121 t＝0.656 t＝0.864 χ2＝0.827 t＝1.773
P值   0.559 0.728 0.512 0.389 0.363 0.078
组别 例数 早产[例数(%)] 新生儿并发症[例数(%)]
窒息a 呼吸窘迫综合征a 肺炎a 羊水胎粪污染 脓毒症 低血糖症a
NEC组 138 90(65.2) 14(10.1) 13(9.4) 10(7.3) 37(26.8) 44(31.9) 8(5.8)
非NEC组 65 26(40.0) 1(1.5) 1(1.5) 0(0) 5(7.7) 6(9.2) 3(4.6)
统计量   χ2＝11.474 χ2＝3.608 χ2＝3.136 χ2＝3.528 χ2＝9.844 χ2＝12.215 χ2<0.001
P值   0.001 0.058 0.077 0.060 0.002 <0.001 0.988
组别 例数 新生儿并发症[例数(%)] 母亲妊娠期合并症[例数(%)]
感染性休克a 高胆红素血症a 妊娠期高血压疾病 妊娠期糖尿病 妊娠期胆汁淤积症a 胎膜早破 感染b
NEC组 138 7(5.1) 5(3.6) 15(10.9) 48(34.8) 7(5.1) 48(34.8) 34(24.6)
非NEC组 65 1(1.5) 1(1.5) 5(7.7) 11(16.9) 2(3.1) 13(20.0) 8(12.3)
统计量   χ2＝1.458 χ2＝0.140 χ2＝0.502 χ2＝6.836 χ2＝0.078 χ2＝5.653 χ2＝4.094
P值   0.412 0.708 0.479 0.009 0.780 0.017 0.043
组别 例数 喂养方式[例数(%)] 开奶时间(生后min，±s) 预防性使用益生菌[例数(%)]c 入院时血清IL-6水平(ng/mL，±s)
母乳喂养 人工喂养 混合喂养
NEC组 138 27(19.6) 81(58.7) 30(21.7) 34.8±5.5 20(14.5) 8.7±1.9
非NEC组 65 33(50.8) 26(40.0) 6(9.2) 30.3±5.3 28(43.1) 3.1±1.5
统计量   χ2＝21.385 t＝5.502 χ2＝19.997 t＝20.885
P值   <0.001 <0.001 <0.001 <0.001
表2 影响NEC发生的多因素非条件logistic回归分析结果a
影响因素 B SE Wald值 P值 OR值 OR值95%CI
早产(vs足月产) 0.965 0.886 1.186 0.035 2.624 1.269~3.451
羊水胎粪污染(vs无羊水胎粪污染) 0.614 0.562 1.192 0.028 1.847 1.358~2.634
新生儿脓毒症(vs无脓毒症) 1.388 1.351 1.055 0.022 4.006 3.039~5.138
母亲妊娠期糖尿病(vs无该病) 0.503 0.428 1.379 0.012 1.653 1.142~2.869
非单纯母乳喂养(vs母乳喂养) 0.392 0.349 1.262 0.006 1.480 1.028~2.366
未预防性使用益生菌(vs预防性使用益生菌) 1.199 1.053 1.297 <0.001 3.318 1.235~3.959
血清IL-6>6.25 ng/mL(vs血清IL-6≤6.25 ng/mL) 0.839 0.796 1.111 0.018 2.314 1.497~4.247
常数项 －2.830 1.088 6.767 <0.001 0.059 —
表3 NEC疑似亚组与确诊亚组新生儿腹部超声检查结果比较[例数(%)]
组别 例数 肠壁增厚 肠壁间积气 门静脉积气 肠管扩张 肠管充气减少 腹腔游离气体a 肠道蠕动减慢 肠道蠕动消失 腹腔积液(透声好) 腹腔积液(透声差) 肠壁血流灌注减少
NEC疑似亚组 79 14(17.7) 30(38.0) 3(3.8) 19(24.1) 22(27.9) 0(0) 39(49.4) 8(10.1) 36(45.6) 6(7.6) 0(0)
NEC确诊亚组 59 32(54.2) 24(40.7) 27(45.8) 24(40.7) 27(45.8) 3(5.1) 22(37.3) 19(32.2) 24(40.7) 35(59.3) 23(39.0)
χ2值   20.266 0.104 34.962 4.353 4.734 2.063 1.998 10.460 0.329 43.275 36.956
P值   <0.001 0.748 <0.001 0.037 0.030 0.151 0.158 0.001 0.566 <0.001 <0.001
图1 腹部超声、血清IL-6水平检测及二者联合检测，诊断NEC的ROC曲线比较注：IL为白细胞介素，NEC为坏死性小肠结肠炎。ROC为受试者工作特征
表4 NEC内科治疗亚组和手术亚组新生儿腹部超声检测结果及血清IL-6水平比较
组别 例数 肠壁增厚[例数(%)] 肠壁间积气[例数(%)] 门静脉积气[例数(%)] 肠管扩张[例数(%)] 肠管充气减少[例数(%)] 腹腔游离气体[例数(%)]a
NEC内科治疗亚组 94 17(18.1) 36(38.3) 15(16.0) 21(22.3) 26(27.7) 0(0)
NEC手术亚组 44 22(50.0) 18(40.9) 13(29.6) 19(43.2) 20(45.5) 2(4.6)
统计量   χ2＝15.057 χ2＝0.086 χ2＝3.422 χ2＝6.325 χ2＝4.271 —
P值   <0.001 0.770 0.064 0.012 0.039 0.183
组别   肠道蠕动减慢[例数(%)] 肠道蠕动消失[例数(%)] 腹腔积液(透声好) [例数(%)] 腹腔积液(透声差) [例数(%)] 肠壁血流灌注减少[例数(%)] 入院时血清IL-6水平(ng/mL，±s)
NEC内科治疗亚组 94 38(40.4) 3(3.2) 40(42.6) 7(7.5) 10(10.6) 7.5±1.7
NEC手术亚组 44 21(47.7) 17(38.6) 20(45.5) 24(54.6) 10(22.7) 9.3±1.8
统计量   χ2＝0.653 χ2＝30.385 χ2＝0.103 χ2＝38.171 χ2＝3.534 t＝5.689
P值   0.419 <0.001 0.749 <0.001 0.060 <0.001
图2 A、B、C亚组NEC患儿生存曲线分析注：A亚组患儿为血清IL-6>6.25 ng/mL＋肠壁增厚＋肠管扩张＋肠管充气减少＋肠道蠕动消失＋腹腔积液(透声差)；B亚组患儿为血清IL-6≤6.25 ng/mL＋无肠壁增厚＋无肠管扩张＋无肠管充气减少＋无肠道蠕动消失＋无腹腔积液(透声差)；C亚组患儿为A、B亚组之外的其余NEC患儿。NEC为坏死性小肠结肠炎，IL为白细胞介素
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