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.
Background
Necrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis/prevention. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated the impact of two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP).
Methods
Infants born ≤32 weeks and/or ≤1500g were prospectively enrolled from 2009–2012. Starting within 72 hours of birth, 5 weekly whole blood specimens were collected to measure RP and serum iAP. Additional specimens were obtained at NEC onset (Bell stage II or III) and 24 hours later. Dichotomous cut-points for both biomarkers sought to maximize sensitivity. The Mann-Whitney U test highlighted differences in median biomarker levels between NEC and non-NEC infants. Chi-square or Fisher’s exact test highlighted categorical differences. The Kaplan-Meier method and Logrank test estimated the probability of developing NEC. The Cox proportional hazards model estimated hazard ratios.
Results
Of 177 infants, 8.5% developed NEC. Of these, 40% required surgery, 20% expired before discharge, 93% had “low” RP (≤2.3%), and 60% had high iAP (>0 U/L). Infants with “low” RP were significantly more likely to develop NEC [HR=11.0 (1.4–83); p=0.02], while those with “high” iAP showed a similar trend [HR=5.2 (0.7–42); p=0.12]. Median iAP levels were significantly higher at week 4 (p=0.02), preceding the average time to NEC onset by one week (35.7 ± 17.3 days).
Conclusion
Decreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.
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