Serum Markers of Necrotizing Enterocolitis: A Systematic Review

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The aim of the study was to systematically review the diagnostic utility of serum biomarkers for the diagnosis of necrotizing enterocolitis (NEC).


We conducted an electronic and manual search of the available evidence. We included studies reporting data on the diagnostic accuracy of “serum” biomarkers for the diagnosis of NEC, available until January 2016.


We selected 22 studies from the 1296 articles retrieved. Only S100 A8/A9 protein and apolipoprotein-CII showed high sensitivity (100% and 96.4%, respectively) and specificity (90% and 95%, respectively) in the studies using Bell stage II NEC as target condition. High sensitivity and specificity were reported for interleukin-10 (100% and 90%), interleukin1-receptor antagonist (100% and 91.7%), intestinal fatty acid–binding protein (100% and 91%) and ischemia-modified albumin (94.7% and 92%), when tested to predict the evolution from definite to advanced NEC. Given the amount of uncertainty, the limited availability of data and heterogeneity among the populations in the different studies, we were unable to perform a meta-analysis. Major concerns about the applicability stemmed from the spectrum of patients enrolled and the inclusion of diseases different from Bell stage ≥2 NEC as target conditions.


We identified only few markers with good diagnostic accuracy and found an overall low quality of the studies on serum NEC biomarkers. In conclusion, data supporting their use are insufficient.

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