Fecal High-Mobility Group Box 1 as a Marker of Early Stage of Necrotizing Enterocolitis in Preterm Neonates

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.

Selective targeting of MD2 attenuates intestinal inflammation and prevents neonatal necrotizing enterocolitis by suppressing TLR4 signaling

“…HMGB1 is an important proinflammatory cytokine and inflammatory transmitter (65-67). The increased expression of HMGB1 leads to enhancement of the inflammatory response in the tissue and promotes the development of NEC (68,69). The present study showed that targeting MD2 to block the activation of TLR4 reduces excessive inflammatory storms, intestinal barrier function injury and intestinal cell apoptosis in NEC patients.…”

“…HMGB1 is an important proinflammatory cytokine and inflammatory transmitter ( 65 – 67 ). The increased expression of HMGB1 leads to enhancement of the inflammatory response in the tissue and promotes the development of NEC ( 68 , 69 ).…”

Complementary Feeding and Growth in Infants Born Preterm: A 12 Months Follow-Up Study

“…Morbidity was defined as the presence of at least one of the major prematurity-related complications, such as necrotizing enterocolitis (NEC) Bell-Stage ≥ 2, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), sepsis proven by positive culture, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD) of at least moderate grade. Diagnosis of NEC, BPD, IVH, PVL, ROP, and sepsis were performed according to standard criteria by physicians caring for the babies and were blinded of the study aims [ 22 , 23 , 24 , 25 , 26 ]. Extrauterine growth restriction (EUGR) with longitudinal definition was defined as the loss of 1 standard deviation from birth to 36 weeks of PMA [ 27 ].…”

Early Enteral Feeding Improves Tolerance of Parenteral Nutrition in Preterm Newborns

“…Specifically, we collected data regarding intrauterine growth restriction (IUGR), pregnancy-induced hypertension, antenatal corticosteroids administration (as an intramuscular steroid cycle in two doses of 12 mg over a 24 h period), GA, birth weight, to be small for GA (SGA), sex, type of delivery, twin's pregnancy, pH at birth, Apgar score at 5 min after birth and respiratory distress syndrome. Data regarding nutritional intake and prematurity-related morbidities (NEC, bronchopulmonary dysplasia, sepsis proven by positive culture, retinopathy of prematurity, periventricular leukomalacia and intraventricular hemorrhage before and after 7 days of age) [27][28][29][30][31] were also collected during the entire hospital stay.…”