Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention? (original) (raw)
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Recent Potential Noninvasive Biomarkers in Necrotizing Enterocolitis
Gastroenterology Research and Practice, 2019
Necrotizing enterocolitis (NEC) is a rare but devastating gastrointestinal disease that predominately affects preterm neonates. Numerous studies have revealed that NEC is strongly associated with very low birth weight, degree of prematurity, formula feeding, infection, hypoxic/ischemic injury, and enteric dysbiosis. Given these clinical associations, the search for a deeper understanding of disease pathogenesis has led to an intense interest in the discovery and development of noninvasive biomarkers of NEC from stool, urine, and serum. Biomarkers for NEC may serve at least two general purposes of urgent unmet need: to improve diagnostic accuracy and disease prediction and to reveal the mechanism of the disease. This review will provide an overview of recent research focused on clinical NEC and highlight the advances that were made within the past five years towards the development of noninvasive diagnostic biomarkers.
Annals of Surgery, 2010
Necrotizing enterocolitis (NEC) remains one of the most frequent gastrointestinal diseases in the neonatal intensive care unit, with a continuing unacceptable high mortality and morbidity rates. Up to 20% to 40% of infants with NEC will need surgical intervention at some point. Although the exact pathophysiology is not yet elucidated, prematurity, use of formula feeding, and an altered intestinal microbiota are supposed to induce an inflammatory response of the immature intestine. The clinical picture of NEC has been well described. However, an early diagnosis and differentiation against sepsis is challenging. Besides, it is difficult to timely identify NEC cases that will deteriorate and need surgical intervention. This may interfere with the most optimal treatment of infants with NEC. In this review, we discuss the pathogenesis, diagnosis, and treatment of NEC with a focus on the role of microbiota in the development of NEC. An overview of different clinical prediction models and biomarkers is given. Some of these are promising tools for accurate diagnosis of NEC and selection of appropriate therapy. (Inflamm Bowel Dis 2015;21:436-444)
2015
Necrotizing enterocolitis (NEC) is an inflammatory disease of the intestine primarily affecting preterm infants. Currently, the diagnosis of NEC is based on a constellation of non-specific clinical symptoms and signs, radiologic findings, and laboratory data (Bell's staging criteria). However, a definitive diagnosis of NEC is difficult because of its similarity in presentation to other clinical conditions. Biomarkers measured in stool samples will better reflect inflammation and pathology specific to the intestine. Certain stool markers are able to identify inflammatory bowel disease in pediatric and …
Frontiers in Pediatrics, 2021
Background: Necrotizing enterocolitis (NEC) is a fatal disease where current diagnostic tools are insufficient for preventing NEC. Early predictive biomarkers could be beneficial in identifying infants at high risk of developing NEC.Objective: To explore early biomarkers for predicting NEC in extremely preterm infants (EPIs).Methods: Blood samples were collected on day 2 (median 1.7; range 1.5–2.0) from 40 EPI (median 25 gestational weeks; range 22–27): 11 developed NEC and 29 did not (controls). In each infant, 189 inflammatory, oncological, and vascular proteomic biomarkers were quantified through Proximity Extension Assay. Biomarker expression and clinical data were compared between the NEC group and Controls. Based on biomarker differences, controls were sorted automatically into three subgroups (1, 2, and 3) by a two-dimensional hierarchical clustering analysis.Results: None of the biomarkers differed in expression between all controls and the NEC group. Two biomarkers were hig...
Frontiers in Pediatrics, 2020
Necrotizing Enterocolitis (NEC) is a catastrophic disease affecting predominantly premature infants and is characterized by high mortality and serious long-term consequences. Traditionally, diagnosis of NEC is based on clinical and radiological findings, which, however, are non-specific for NEC, thus confusing differential diagnosis of other conditions such as neonatal sepsis and spontaneous intestinal perforation. In addition, by the time clinical and radiological findings become apparent, NEC has already progressed to an advanced stage. During the last three decades, a lot of research has focused on the discovery of biomarkers, which could accurately predict and make an early diagnosis of NEC. Biomarkers used thus far in clinical practice include acute phase proteins, inflammation mediators, and molecules involved in the immune response. However, none has been proven accurate enough to predict and make an early diagnosis of NEC or discriminate clinical from surgical NEC or other n...
Biomarkers for necrotizing enterocolitis and sepsis
2012
Aspects of the invention include methods, compositions, and kits for diagnosing Necrotizing Enterocolitis (NEC), for diagnosing sepsis, for providing a prognosis for a patient with NEC, and for predicting responsiveness of a patient with NEC to medical intervention. These methods find use in a number of applications, such as diagnosing and treating infants who are suspected of having NEC, intestinal perforation (IP), or sepsis.
Necrotizing enterocolitis is associated with neonatal intestinal injury
Journal of Pediatric Surgery, 2011
PURPOSE: We hypothesized that a subset of premature newborns has subclinical, intestinal mucosal compromise that predisposes to the development of necrotizing enterocolitis (NEC) days or weeks later. METHODS: Fifty-five newborns of 23 to 36 weeks' gestational age were identified, and urine was collected over the first 90 hours of life. The urinary concentration of intestinal fatty acid binding protein (iFABP(u)), a sensitive marker for intestinal injury, was determined. The diagnosis of NEC was based upon clinical condition, pathology, and/or imaging findings. RESULTS: Neonatal iFABP(u) exceeded 800 pg/mL in 27 subjects, including 9 of 9 who subsequently developed stage 2 or 3 NEC. This degree of iFABP(u) elevation, but not asphyxia, was significantly associated with the development of NEC (P < .01). CONCLUSION: In this population of premature newborns, there was a substantial incidence of intestinal mucosal compromise. All infants who subsequently developed stage 2 or 3 NEC had an elevated iFABP(u). This finding suggests a model for the pathogenesis of some cases of NEC, whereby perinatal mucosal injury predisposes to further damage when feedings are initiated. In addition, neonatal iFABP(u) assessment may represent a tool to identify infants at the highest risk for NEC and allow for the institution of focused, preventive measures.
Journal of Clinical Investigation, 2010
Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.