Fecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of necrotizing enterocolitis: A prospective study

Abstract

Background and purposeNecrotizing enterocolitis (NEC) is a critical gastrointestinal disease. We aim to explore the value of fecal human β-defensin 2 (HBD-2), Claudin-3, high-mobility group box-1 protein (HMGB-1), and resistin-like molecule β (Relmβ) as well as some laboratory metrics to predict the deterioration of NEC.MethodsInfants diagnosed with NEC at Stage II were enrolled in our study. Those who progressed to Stage III were included in the Stage III group and the rest were included in the Stage II group. Clinical data and laboratory metrics of the infants were collected. Fecal samples of HBD2, HMGB-1, Claudin-3, and Relmβ collected during their enrollment were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Student's t-test, the Mann–Whitney U test, the chi-square test, receiver operating characteristic (ROC), and logistic regression analysis were performed.ResultsSixty infants diagnosed with NEC at Stage II were enrolled in our study, with 27 in the Stage III group (n = 27) and 33 in the Stage II group (n = 33). Although many of these NEC cases were late preterm and term infants, the infants in the Stage III group had a lower gestational age (P < 0.05). The incidence of gestational diabetes mellitus, peritonitis, intestinal adhesion, and sepsis was higher and more infants in the Stage III group underwent surgeries (P < 0.05). The levels of HBD-2 and Claudin-3 were higher and neutrophil count was lower in the Stage III group than in the Stage II Group, and the area under the curve (AUC) was 0.754, 0,755, and 0.666, respectively (P < 0.05). HBD-2 ≥ 1649.02 ng/g and Claudin-3 ≥ 2488.71 pg/g were included in the multivariate stepwise logistic regression analysis (P < 0.05), and the AUC of the model was 0.805 (95% CI: 0.688–0.922).ConclusionFecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of NEC from Stage II to Stage III.

Neonatal complicated intraabdominal infection

“…As such, a specific biomarker or panel of biomarkers to specifically identify NEC would be ideal. Investigations continue for biomarkers of NEC, but widespread clinical application of these markers is limited (Table 1) [15 ▪ ,16–20]. Faecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of NEC from Stage II to Stage III but will need further validation [16].…”

Chromatin as alarmins in necrotizing enterocolitis

“…Patients with NEC have been shown to have higher expression of HMGB1 than healthy control counterparts (19,27). Levels of HMGB1 were not substantially different in patients with Stage II or Stage III NEC (when measured in the stool), or patients who were managed medically or surgically (when measured in the serum) (91,92). Nevertheless, HMGB1 levels in stool samples were higher in preterm neonates compared to full-term neonates with birth weight less than 2.5 kg, and early HMGB1 fecal levels were predictive of NEC risk, thus implicating stool HMGB1 as a potential clinical biomarker in this disease (29).…”