The relationship between reticulated platelets, intestinal alkaline phosphatase, and necrotizing enterocolitis

Abstract

BackgroundNecrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP). MethodsInfants born ≤32weeks and/or ≤1500g were prospectively enrolled from 2009 to 2012. Starting within 72hours 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 24hours later. Dichotomous cut-points were calculated for both biomarkers. Non-parametric (Mann-Whitney) and Chi-square tests were used to test differences between groups. Differences in Kaplan-Meier curves were examined by log-rank test. The Cox proportional hazards model estimated hazard ratios. ResultsA total of 177 infants were enrolled in the study, 15 (8.5%) of which developed NEC (40% required surgery and 20% died). 14 (93%) NEC infants had “low” (≤2.3%) reticulated platelets, and 9 (60%) had “high” iAP (>0 U/L) in at least one sample before onset. Infants with “low” RP were significantly more likely to develop NEC [HR=11.0 (1.4–83); P=0.02]. Infants with “high” iAP were at increased risk for NEC, although not significant [HR=5.2 (0.7–42); P=0.12]. Median iAP levels were significantly higher at week 4 preceding the average time to NEC onset by one week (35.7±17.3days; P=0.02). ConclusionDecreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.