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

Abstract

ObjectiveNecrotizing 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.Patients and methodsWe 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 (AMC) were recorded. Diagnostic accuracy of AMC values was tested using receiver-operator characteristics (ROC).ResultsWe compared 69 cases and 257 controls (median 27 weeks, range 26–29 in both groups). In stage II NEC, AMC decreased from median 1.7 × 109/L (interquartile range (IQR) 0.98–2.4) to 0.8 (IQR 0.62–2.1); p <0.05. In stage III NEC, monocyte counts decreased from median 2.1 × 109/L (IQR 0.1.5–3.2) to 0.8 (IQR 0.6–1.9); p <0.05. There was no change in AMC 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 AMC of >20% indicated NEC with sensitivity of 0.70 (95% CI 0.57–0.81) and specificity of 0.71 (95% CI 0.64–0.77).ConclusionsWe have identified a fall in blood monocyte concentration as a novel biomarker for NEC in VLBW infants.

Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis

“…These findings are consistent with existing data from preclinical and clinical studies on cytokine expression in plasma and tissue samples (6, 22–24). Increased expression of the leukocyte receptors CD14 and CD11b can be explained by the monocyte/macrophage infiltration in NEC lesions (6, 7, 21, 25). We also detected increased NF-κB1 and IκB expression in our murine and human datasets, which is consistent with existing information that single nucleotide polymorphisms (SNPs) of NF-κB1 (g.-24519delATTG) and IκB (g.-1004A>G) are over-represented in patients with NEC.…”

Pathogenesis of NEC: Role of the innate and adaptive immune response

“…During the intestinal damage that accompanies NEC, blood monocytes are recruited to the damaged intestine and an acute drop in blood monocyte counts can be observed and may be useful as a biomarker for NEC in VLBW infants 236 . After entering the damaged intestine, blood monocytes rapidly differentiate into pro-inflammatory M1-type macrophages.…”

Immunologic and Hematological Abnormalities in Necrotizing Enterocolitis

“…142,143 Because preterm infants have a limited circulating monocyte pool 144 and lack significant reservoirs of mature monocytes in the bone marrow or elsewhere, 145 we asked whether the migration of circulating monocytes into NEC lesions could result in an acute drop in peripheral blood monocyte counts that may distinguish early NEC from other causes of feeding intolerance. 146 We compared the absolute monocyte counts (AMC) at the onset of feeding intolerance with the last available pre- symptomatic AMC. In patients who developed stage II NEC, the AMC fell from median 1.7 × 10 9 /L (interquartile range, IQR 0.98-2.4) to median 0.8 (IQR 0.62-2.1, p <0.05), whereas in those who developed stage III NEC dropped their AMCs from median 2.1 × 10 9 /L (IQR 0.15-3.2) to median 0.8 (IQR 0.6-1.9, p <0.05).…”