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粪便钙卫蛋白对新生儿坏死性小肠结肠炎诊断作用的Meta分析
谢艳秋, 任常军, 王雄, 相淑雯, 王小星, 郝玲
中国当代儿科杂志 ›› 2021, Vol. 23 ›› Issue (4) : 381-389.
PDF(1932 KB)
PDF(1932 KB)
粪便钙卫蛋白对新生儿坏死性小肠结肠炎诊断作用的Meta分析
Role of fecal calprotectin in the diagnosis of neonatal necrotizing enterocolitis: a Meta analysis
目的 通过Meta分析的方法探讨粪便钙卫蛋白（FC）对新生儿坏死性小肠结肠炎（NEC）的诊断作用。方法 检索Web of Science、Cochrane Library，PubMed、Embase、中国知网（CNKI）、维普期刊数据库、万方数据库、中国生物医学文献数据库，并结合手动检索作为补充，搜索时间为建库至2020年5月。采用QUADAS标准评估纳入文献的质量；采用Meta-Disc 1.4和Stata 15.0软件行Meta分析，包括评价特异度、敏感度、似然比和诊断比值比，进行敏感性分析及异质性测试，绘制综合受试者工作特征（SROC）曲线及Fagan图。结果 共纳入15篇文献，包括1 719例新生儿。其中，低质量文献4篇，高质量文献2篇，其余均为中等质量。纳入研究间异质性较高，不存在阈值效应及发表偏倚。应用随机效应模型分析结果显示：FC对NEC诊断的汇总特异度、灵敏度分别为0.80（95% CI：0.78~0.82）、0.86（95% CI：0.83~0.89），阴性似然比、阳性似然比、诊断比值比分别为0.19（95% CI：0.14~0.26）、4.71（95% CI：3.57~6.23）、29.56（95% CI：17.98~48.61）。SROC曲线下面积为0.9131，Q*指数为0.8456。Fagan图显示FC不增高时NEC发生概率为13%，FC增高时NEC发生概率提高为86%。Meta回归分析发现异质性来源于其他非协变量因素。结论 FC对NEC的早期诊断具有较高的潜力及效能。FC测定可用于NEC的诊断，但应与临床表现及其他相关实验室检查相结合。
Objective To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis. Methods Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted. Results A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95%CI:0.78-0.82) and a sensitivity of 0.86 (95%CI:0.83-0.89) in the diagnosis of NEC, with a negative likelihood ratio of 0.19 (95%CI:0.14-0.26), a positive likelihood ratio of 4.71 (95%CI:3.57-6.23), and a diagnostic odds ratio of 29.56 (95%CI:17.98-48.61). The area under the SROC curve was 0.9131 and the Q* index was 0.8456. The Fagan diagram showed that the post-test probability of NEC indicated by negative FC was 13%, while that indicated by positive FC was 86%. The Meta regression analysis showed that the heterogeneity came from other non-threshold factors. Conclusions FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.
坏死性小肠结肠炎 / 钙卫蛋白 / 诊断价值 / Meta分析 / 新生儿
Necrotizing enterocolitis / Calprotectin / Diagnosis / Meta analysis / Neonate
[1] Knell J, Han SM, Jaksic T, et al. Current status of necrotizing enterocolitis[J]. Curr Probl Surg, 2019, 56(1):11-38.
[2] Bellodas Sanchez J, Kadrofske M. Necrotizing enterocolitis[J]. Neurogastroenterol Motil, 2019, 31(3):e13569.
[3] Qian T, Zhang R, Zhu L, et al. Necrotizing enterocolitis in low birth weight infants in China:mortality risk factors expressed by birth weight categories[J]. Pediatr Neonatol, 2017, 58(6):509-515.
[4] Thakkar HS, Lakhoo K. Necrotizing enterocolitis[J]. Surgery (Oxford), 2019, 37(11):628-631.
[5] Garg BD, Sharma D, Bansal A. Biomarkers of necrotizing enterocolitis:a review of literature[J]. J Matern Fetal Neonatal Med, 2018, 31(22):3051-3064.
[6] Ayling, RM, Kok K. Fecal calprotectin[M]//Makowski GS. Advances in clinical chemistry. Amsterdam:Elsevier, 2018, 87:161-190.
[7] Goldstein GP, Sylvester KG. Biomarker discovery and utility in necrotizing enterocolitis[J]. Clin Perinatol, 2019, 46(1):1-17.
[8] MacQueen BC, Christensen RD, Yost CC, et al. Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps[J]. J Perinatol, 2016, 36(10):862-869.
[9] Vernia F, Di Ruscio M, Stefanelli G, et al. Is fecal calprotectin an accurate marker in the management of Crohn's disease?[J]. J Gastroenterol Hepatol, 2020, 35(3):390-400.
[10] Heida A, Park KT, van Rheenen PF. Clinical utility of fecal calprotectin monitoring in asymptomatic patients with inflammatory bowel disease:a systematic review and practical guide[J]. Inflamm Bowel Dis, 2017, 23(6):894-902.
[11] Wang KW, Tao GZ, Sun Z, et al. Recent potential noninvasive biomarkers in necrotizing enterocolitis[J]. Gastroenterol Res Pract, 2019, 2019:8413698.
[12] Whiting PF, Weswood ME, Rutjes AW, 等. QUADAS评价:一种用于诊断性研究的质量评价工具(修订版)[J]. 中国循证医学杂志, 2007, 7(7):531-536.
[13] 田云粉, 李利, 米弘瑛, 等. 肠型脂肪酸结合蛋白和粪钙卫蛋白联合检测在足月新生儿坏死性小肠结肠炎中的应用价值[J]. 中国当代儿科杂志, 2016, 18(11):1080-1083.
[14] 周金君, 李双双, 张小华, 等. 肠脂酸结合蛋白联合粪钙卫蛋白检测在新生儿坏死性小肠结肠炎中的意义[J]. 世界最新医学信息文摘, 2018, 18(57):157.
[15] 万倩. 粪钙卫蛋白与新生儿坏死性小肠结肠炎的相关性研究[D]. 兰州:兰州大学, 2014.
[16] 赖淑华, 杨长仪. 粪钙卫蛋白在早期诊断早产儿坏死性小肠结肠炎中的临床价值[J]. 海峡预防医学杂志, 2017, 23(1):98-101.
[17] 姜燕, 李和勤, 白亚飞, 等. 尿肠型脂肪酸结合蛋白与粪钙卫蛋白在诊断早产儿喂养不耐受及坏死性小肠结肠炎中的价值[J]. 广西医学, 2016, 38(5):660-663.
[18] Zhang M, Zhang XT, Zhang JY. Diagnostic value of fecal calprotectin in preterm infants with necrotizing enterocolitis[J]. Clin Lab, 2016, 62(5):863-869.
[19] Elfarargy MS, El Farargy MS, Atef MM, et al. Early biomarkers in neonatal necrotizing enterocolitis:a pilot study[J]. J Popul Ther Clin Pharmacol, 2019, 26(3):e1-e8.
[20] Barekatain B, Saneian H, Ebrahimi A, et al. Evaluation and comparison of stool calprotectin level in necrotizing enterocolitis infected and noninfected neonates of <1500 g[J]. J Clin Neonatol, 2019, 8(2):90-95.
[21] Zoppelli L, Güttel C, Bittrich HJ, et al. Fecal calprotectin concentrations in premature infants have a lower limit and show postnatal and gestational age dependence[J]. Neonatology, 2012, 102(1):68-74.
[22] Abdelkader M, Mesbah BE, Khashana A. Fecal calprotectin level in neonates with necrotizing enterocolitis[J]. Iran J Neonatol, 2019, 10(3):7-13.
[23] Aydemir O, Aydemir C, Sarikabadayi YU, et al. Fecal calprotectin levels are increased in infants with necrotizing enterocolitis[J]. J Matern Fetal Neonatal Med, 2012, 25(11):2237-2241.
[24] Campeotto F, Baldassarre M, Butel MJ, et al. Fecal calprotectin:cutoff values for identifying intestinal distress in preterm infants[J]. J Pediatr Gastroenterol Nutr, 2009, 48(4):507-510.
[25] Thuijls G, Derikx JP, van Wijck K, et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis[J]. Ann Surg, 2010, 251(6):1174-1180.
[26] Reisinger KW, Van der Zee DC, Brouwers HA, et al. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis[J]. J Pediatr Surg, 2012, 47(9):1640-1645.
[27] MacQueen BC, Christensen RD, Yost CC, et al. Reference intervals for stool calprotectin in preterm neonates and their utility for the diagnosis of necrotizing enterocolitis[J]. J Perinatol, 2018, 38(10):1379-1385.
[28] Zhu XL, Tang XG, Qu F, et al. Bifidobacterium may benefit the prevention of necrotizing enterocolitis in preterm infants:a systematic review and meta-analysis[J]. Int J Surg, 2019, 61:17-25.
[29] Underwood MA. Probiotics and the prevention of necrotizing enterocolitis[J]. J Pediatr Surg, 2019, 54(3):405-412.
[30] Albanna EA, Ahmed HS, Awad HA. Stool calprotectin in necrotizing enterocolitis[J]. J Clin Neonatol, 2014, 3(1):16-19.
[31] Yoon JM, Park JY, Ko KO, et al. Fecal calprotectin concentration in neonatal necrotizing enterocolitis[J]. Korean J Pediatr, 2014, 57(8):351-356.
