Acute drop in blood monocyte count differentiates NEC from other causes of feeding intolerance

Abstract

Objective: Necrotizing enterocolitis (NEC) is characterized by macrophage infiltration into affected tissues. Because intestinal macrophages are derived from recruitment and in situ differentiation of blood monocytes in the gut mucosa, we hypothesized that increased recruitment of monocytes to the intestine during NEC reduces the blood monocyte concentration and that this fall in blood monocytes can be a useful biomarker for NEC.

Study design: We reviewed medical records of very-low-birth-weight (VLBW) infants treated for NEC and compared them with a matched control group comprised of infants with feeding intolerance but no signs of NEC. Clinical characteristics and absolute monocyte counts (AMCs) were recorded. Diagnostic accuracy of AMC values was tested using receiver-operator characteristics (ROC).

Result: We compared 69 cases and 257 controls (median 27 weeks, range 26 to 29 in both the groups). In stage II NEC, AMCs decreased from median 1.7 × 10(9) l(-1) (interquartile range (IQR) 0.98 to 2.4) to 0.8 (IQR 0.62 to 2.1); P < 0.05. In stage III NEC, monocyte counts decreased from median 2.1 × 10(9) l(-1) (IQR 0.1.5 to 3.2) to 0.8 (IQR 0.6 to 1.9); P < 0.05. There was no change in AMCs in control infants. ROC of AMC values showed a diagnostic accuracy (area under the curve) of 0.76. In a given infant with feeding intolerance, a drop in AMCs of > 20% indicated NEC with sensitivity of 0.70 (95% confidence interval (CI) 0.57 to 0.81) and specificity of 0.71 (95% CI 0.64 to 0.77).

Conclusion: We have identified a fall in blood monocyte concentration as a novel biomarker for NEC in VLBW infants.

Figure 1. Longitudinal change in peripheral blood AMC in control and NEC groups

Box-whisker plots show AMC in (A) controls, (B) infants with NEC stage II, and (C) those with NEC stage III. Data were compared by repeated measures ANOVA on ranks with Dunnett’s test using AMC prior to feeding intolerance as the comparison group.

Figure 2. Diagnostic accuracy of decreased peripheral blood AMC as a test for NEC

Receiver-operator characteristics of the ratio of AMC in infants at the time of feeding intolerance vs. AMC in the most recent CBC drawn prior to the onset of feeding intolerance show that a >20% drop in AMC correctly identified NEC in 76% cases (depicted by the area under the curve). A cut-off value of 0.8 (marked by broken lines in the figure) provided 70% sensitivity and 70.6% specificity.