Abstract
Introduction: An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC.Materials and Methods: A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital “Umberto I” in Rome, from July 2015 to December 2016. Stool samples obtained from cases (preterm newborns with NEC) and controls (newborns without NEC) were collected at the enrolment (T0) and within 7–14 days after the first sample collection (T1). HMGB1, extracted and measured with western blot, was reported as densitometry units (DUS).Results: HMGB1 levels in 30 cases (n = 28—Bell stage 1, n = 2 Bell stage 2) were higher [T0: 21,462 DUS (95% CI, 16,370–26,553 DUS)—T1: 17,533 DUS (95% CI, 13,052–22,014 DUS)] than in 30 preterm controls [T0: 9,446 DUS (95% CI, 6,147–12,746 DUS)—T1: 9,261 DUS (95% CI, 5,126–13,396 DUS), p < 0.001). Preterm newborns showed significant higher levels of HMGB1 (15,690 DUS (95% CI, 11,929–19,451 DUS)] in comparison with 30 full-term neonates with birth weight >2,500 g [6,599 DUS (95% CI, 3,141–10,058 DUS), p = 0.003]. Multivariate analysis showed that the risk of NEC was significantly (p = 0.012) related to the HMGB1 fecal levels at T0.Conclusions: We suggest fecal HMGB1 as a reliable marker of early NEC in preterm neonates. This study supports further investigation on the role of fecal HMGB1 assessment in managing preterm newborns at risk of NEC. Further studies are advocated to evaluate diagnostic accuracy of this marker in more severe forms of the disease.
Highlights
An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis
We have previously shown in patients with inflammatory bowel disease (IBD) that fecal high-mobility group box protein 1 (HMGB1) is a robust non-invasive biomarker of mucosal inflammation and healing, suggesting its potential role in the diagnostic approach and monitoring intestinal inflammation in children [24, 25]
Fecal HMGB1 values in the first week of life in newborns at term of gestation or with birth weight (BW) >2,500 g [gestational age (GA), 38 weeks; BW, 3,194 g] were significantly lower than in preterm newborns or with BW
Summary
An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC. Despite significant improvements have occurred in neonatal intensive care, the administration of enteral feedings in preterm infants is a challenging step [1]. Enteral nutrition (EN) should always be the preferred method in neonatal feeding. The interpretation of early signs of NEC is still an undefined issue in preterm nutritional care, biomarkers helpful in identifying newborns at risk of developing NEC are warranted [5, 8, 11,12,13,14]. No biomarker has sufficient predictive value for clinical purposes [14, 15]
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