Abstract
The present study was undertaken to evaluate the performance of intestinal fatty-acid-binding protein (i-FABP) in the diagnosis of newborn necrotizing enterocolitis (NEC) and prediction of surgical NEC. A comprehensive literature search was performed in PubMed and EMBASE to identify potential relevant studies. QUADAS-2 tool was used to assess the quality of the included studies. The sensitivity, specificity and other measurements of accuracy of i-FABP were pooled. Summary receiver operating characteristic curves (SROC) and area under the curve (AUC) were used to summarize overall diagnostic performance. After screening 150 titles and abstracts, followed by 32 full-text publications, 14 studies were included. The sample size, sensitivity, specificity, diagnostic odds ratio (DOR) and AUC were: plasma i-FABP 217, 0.64(95% CI 0.53 to 0.74), 0.91(95% CI 0.84 to 0.95), 14.22 (95%CI 6.42 to 31.52) and 0.84; urinary i-FABP 211, 0.64(95% CI 0.53 to 0.74), 0.73(95% CI 0.64 to 0.80), 6.35 (95%CI 3.17 to 12.72) and 0.81; urinary i-FABP/Cr 165, 0.78(95% CI 0.65 to 0.88), 0.75(95% CI 0.65 to 0.82), 6.35 (95%CI 3.17 to 12.72) and 0.81; plasma i-FABP for surgical NEC 45, 0.71(95% CI 0.51 to 0.87), 0.76(95% CI 0.50 to 0.93), 7.58 (95%CI 0.87 to 65.82) and 0.80. Plasma i-FABP is a promising biomarker in the diagnosis of NEC with high specificity and DOR; but its usefulness is limited because of medium sensitivity. The urinary i-FABP and urinary i-FABP/Cr add little value in the diagnosis. The findings were somewhat limited by the quality and small size of some of the studies included.
Similar content being viewed by others
References
Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007;92:F193–8.
Benkoe TM, Mechtler TP, Weninger M, Pones M, Rebhandl W, Kasper DC. Serum levels of interleukin-8 and gut-associated biomarkers in diagnosing necrotizing enterocolitis in preterm infants. J Pediatr Surg. 2014;49:1446–51.
Pott J, Hornef M. Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep. 2012;13:684–98.
van de Poll MC, Derikx JP, Buurman WA, et al. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection. World J Surg. 2007;31:2033–8.
Thuijls G, Derikx JP, van Wijck K, et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg. 2010;251:1174–80.
Guthmann F, Borchers T, Wolfrum C, Wustrack T, Bartholomaus S, Spener F. Plasma concentration of intestinal- and liver-FABP in neonates suffering from necrotizing enterocolitis and in healthy preterm neonates. Mol Cell Biochem. 2002;239:227–34.
Schurink M, Kooi EM, Hulzebos CV, et al. Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study. PLoS One. 2015;10:e0121336.
Lieberman JM, Sacchettini J, Marks C, Marks WH. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery. 1997;121:335–42.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.
Derikx JP, Evennett NJ, Degraeuwe PL, et al. Urine based detection of intestinal mucosal cell damage in neonates with suspected necrotising enterocolitis. Gut. 2007;56:1473–5.
Gollin G, Stadie D, Mayhew J, et al. Early detection of impending necrotizing enterocolitis with urinary intestinal fatty acid-binding protein. Neonatology. 2014;106:195–200.
Evennett N, Cerigioni E, Hall NJ, Pierro A, Eaton S. Smooth muscle actin as a novel serologic marker of severe intestinal damage in rat intestinal ischemia-reperfusion and human necrotising enterocolitis. J Surg Res. 2014;191:323–30.
Gregory KE, Winston AB, Yamamoto HS, et al. Urinary intestinal fatty acid binding protein predicts necrotizing enterocolitis. J Pediatr. 2014;164:1486–8.
Ng EW, Poon TC, Lam HS, et al. Gut-associated biomarkers L-FABP, I-FABP, and TFF3 and LIT score for diagnosis of surgical necrotizing enterocolitis in preterm infants. Ann Surg. 2013;258:1111–8.
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 Pediatr Surg. 2012;47:1640–5.
Aydemir C, Dilli D, Oguz SS, et al. Serum intestinal fatty acid binding protein level for early diagnosis and prediction of severity of necrotizing enterocolitis. Early Hum Dev. 2011;87:659–61.
Mannoia K, Boskovic DS, Slater L, Plank MS, Angeles DM, Gollin G. Necrotizing enterocolitis is associated with neonatal intestinal injury. J Pediatr Surg. 2011;46:81–5.
Evennett NJ, Hall NJ, Pierro A, Eaton S. Urinary intestinal fatty acid-binding protein concentration predicts extent of disease in necrotizing enterocolitis. J Pediatr Surg. 2010;45:735–40.
Edelson MB, Sonnino RE, Bagwell CE, Lieberman JM, Marks WH, Rozycki HJ. Plasma intestinal fatty acid binding protein in neonates with necrotizing enterocolitis: a pilot study. J Pediatr Surg. 1999;34:1453–7.
Thuijls G, van Wijck K, Grootjans J, et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann Surg. 2011;253:303–8.
Gollin G, Zieg PM, Cohn SM, Lieberman JM, Marks WH. Intestinal mucosal injury in critically ill surgical patients: preliminary observations. Am Surg. 1999;65:19–21.
Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. J Perinatol. 2003;23:278–85.
Luig M. Lui K; NSW & ACT NICUS group. Epidemiology of necrotizing enterocolitis–part II: risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41:174–9.
Walter SD, Sinuff T. Studies reporting ROC curves of diagnostic and prediction data can be incorporated into meta-analyses using corresponding odds ratios. J Clin Epidemiol. 2007;60:530–4.
Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. Beta-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52:750–70.
Contributions
GY: Literature search, evaluation of studies, data analysis; YW: Evaluation of studies; GY and YW: Wrote the article; XJ: Guided the research and will act as guarantor for the paper.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
None.
Source of Funding
None.
Rights and permissions
About this article
Cite this article
Yang, G., Wang, Y. & Jiang, X. Diagnostic Value of Intestinal Fatty-Acid-Binding Protein in Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. Indian J Pediatr 83, 1410–1419 (2016). https://doi.org/10.1007/s12098-016-2144-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12098-016-2144-9