Stool Biomarkers May Distinguish Necrotizing Enterocolitis in Infants
Stool samples from preterm infants can distinguish cases of confirmed necrotizing enterocolitis from non-affected infants, according to an ancillary analysis published October 23, 2026, in Pediatric Research (doi: 10.1038/s41390-026-05566-4). As reported by 2 Minute Medicine, the study examined 130 preterm infants born before 32 weeks of gestation in France to evaluate whether noninvasive fecal biomarkers could improve the detection of this severe gastrointestinal emergency.
Necrotizing enterocolitis affects approximately 2 to 7 percent of preterm infants admitted to neonatal intensive care units and carries high mortality rates, particularly when surgical intervention becomes necessary. Initial signs mimic other neonatal conditions such as sepsis and spontaneous intestinal perforation, meaning clinicians frequently confirm the diagnosis only after advanced intestinal injury has already occurred. Management currently relies on supportive measures including bowel rest and antibiotics, alongside preventive strategies such as human milk feeding and probiotic administration depending on local clinical practices.
Biomarker Concentrations in Affected and Control Infants
The study population comprised 42 infants with confirmed necrotizing enterocolitis at Bell stage II or higher and 88 preterm infants without the condition. Both groups shared a median gestational age of 28 weeks, while median birth weight reached 983 grams in the affected group and 973 grams in the control group. Stool collection occurred at the time of diagnosis for infants with the disease and at comparable postnatal ages for those without it, averaging 24 days and 28 days respectively. Out of 142 total collected samples, 12 were excluded due to insufficient material for laboratory testing.
Researchers measured six specific fecal biomarkers using enzyme-linked immunosorbent assay kits: fecal calprotectin, human beta-defensin-2, alpha-1-antitrypsin, secretory immunoglobulin A, cingulin, and eosinophil-derived neurotoxin. Concentrations differed significantly between the two groups for five of the six markers, with only cingulin showing no variation between cohorts. Infants with confirmed disease exhibited higher median concentrations of fecal calprotectin at 198 micrograms per gram compared to 77 micrograms per gram in controls.
Discriminatory Performance of Single and Multimarker Models
Secretory immunoglobulin A demonstrated the strongest individual discrimination between infants with necrotizing enterocolitis and healthy controls, yielding an area under the receiver operating characteristic curve of 0.82. Fecal calprotectin followed with an area under the curve of 0.74, while alpha-1-antitrypsin achieved 0.73. Combining multiple markers yielded modest performance improvements. A four-biomarker model incorporating alpha-1-antitrypsin, eosinophil-derived neurotoxin, human beta-defensin-2, and secretory immunoglobulin A produced an area under the curve of 0.83, while a complete-case model utilizing all six biomarkers reached 0.86 in 108 infants.
Because human milk exposure varied between the two groups at postnatal day three, investigators analyzed secretory immunoglobulin A concentrations relative to feeding type. Infants receiving exclusive donor human milk or exclusive mother’s own milk displayed higher fecal secretory immunoglobulin A levels than those receiving a combination of human milk and infant formula. The authors note that validation is now required in prospective cohorts of infants presenting with clinical signs suspicious for necrotizing enterocolitis alongside competing neonatal diagnoses.
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