Abstract / Summary
Abstract Background Zonulin is an endogenous regulator of intestinal epithelial tight junctions and a biomarker of intestinal permeability. This study evaluated the predictive value of fecal zonulin levels for the early identification of necrotizing enterocolitis (NEC) risk in premature infants. Methods This single-center prospective cohort study included 91 premature infants (gestational age 22–32 weeks) and 25 term controls followed for 2 months. Fecal zonulin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using stool samples collected on postnatal days 3, 7, and 14. The primary receiver operating characteristic (ROC) analysis was performed at the patient level, with a sample-level ROC analysis conducted as a sensitivity analysis. Multivariate logistic regression was performed as an exploratory analysis because of the limited number of NEC events. Results NEC developed in 10 of 91 (11.0%) premature infants at a mean postnatal age of 12.5 ± 0.35 days. Mean fecal zonulin concentrations on postnatal day 7 were significantly higher in infants who subsequently developed NEC than in those who did not (618.4 ± 89.9 ng/mL vs 343.5 ± 76.7 ng/mL; p < 0.05). Patient-level ROC analysis for day 7 fecal zonulin demonstrated an area under the curve (AUC) of 0.81, with 85% sensitivity and 72% specificity at a cutoff value of 490 ng/mL. Sample-level ROC analysis (sensitivity analysis) yielded an AUC of 0.995, with 100% sensitivity and 94.5% specificity at a cutoff value of 548.2 ng/mL. Exploratory multivariate logistic regression identified fecal zonulin as an independent predictor of NEC; however, these findings should be interpreted cautiously because of the limited number of NEC events. Conclusions Elevated fecal zonulin concentrations on postnatal day 7 are associated with subsequent development of NEC in premature infants and may represent a promising noninvasive biomarker for early risk stratification. Larger multicenter studies are warranted to validate these findings.