Optimizing Nutritional Strategies to Prevent Necrotizing Enterocolitis and Growth Failure after Bowel Resection

Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20–50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.

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Challenge in diagnosis of late onset necrotizing enterocolitis in a term infant: a case report

BMC Pediatrics ◽

10.1186/s12887-021-02626-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gunadi ◽

Dian Nirmala Sirait ◽

Aditya Rifqi Fauzi ◽

Ninditya Nugroho ◽

Fadil Fahri ◽

...

Keyword(s):

Ct Scan ◽

Necrotizing Enterocolitis ◽

Intestinal Inflammation ◽

Late Onset ◽

Gastrointestinal Disease ◽

Early Recognition ◽

Ileocecal Valve ◽

Abdominal Distention ◽

Clinical Deterioration ◽

Wall Thickening

Abstract Background Necrotizing enterocolitis (NEC) is a common devastating inflammatory gastrointestinal disease and frequently occurs in premature infants. Here, we reported a case of late-onset NEC in a term neonate with good outcome after surgery for long-term follow-up. Case presentation Ten-week-old male came to emergency unit due to prolonged diarrhea and abdominal distention. He was born at gestational age of 40 weeks with birth weight and Apgar score of 2800 g and 7/8, respectively. He had no history of formula feeding. Two weeks before admitted to the hospital, the patient had frequent diarrhea with fever. He was found lethargic with abdominal distention, absence of bowel sounds and abdominal tenderness. Plain abdominal x-ray and CT scan showed gastric and intestinal dilatation and gasless colon, suggesting a small bowel obstruction, and bowel wall thickening indicating peritonitis, without any free subdiaphragmatic air (pneumoperitoneum). Moreover, the patient did not have a congenital heart disease. While in intensive medical treatment, he showed a continuous clinical deterioration. All findings were suggestive of intestinal inflammation with clinical deterioration, and we decided to perform an emergency exploratory laparotomy and found an ischemia along the jejunoileal with a perforation at 25 cm above the ileocecal valve. Subsequently, we performed a double-barrel ileostomy through a separate incision from the laparotomy. Histopathological findings confirmed the diagnosis of NEC. We closed the stoma at postoperative day 43. The patient was discharged uneventfully a month after stoma closure. Conclusion Abdominal CT scan might be useful to establish an early recognition of late-onset NEC; thus, immediate surgical intervention might be performed to decrease its morbidity and mortality. Moreover, late-onset NEC in term neonates might occur without any risk factors or significant co-morbidities.

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Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain

Science Translational Medicine ◽

10.1126/scitranslmed.aan0237 ◽

2018 ◽

Vol 10 (471) ◽

pp. eaan0237 ◽

Cited By ~ 29

Author(s):

Diego F. Niño ◽

Qinjie Zhou ◽

Yukihiro Yamaguchi ◽

Laura Y. Martin ◽

Sanxia Wang ◽

...

Keyword(s):

Necrotizing Enterocolitis ◽

Microglial Activation ◽

Gastrointestinal Disease ◽

Cognitive Impairments ◽

High Mobility ◽

Neurological Dysfunction ◽

Mucosal Inflammation ◽

Signaling Axis ◽

The Brain

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.

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Long-term follow-up after bowel resection for necrotizing enterocolitis: Factors affecting outcome

Journal of Pediatric Surgery ◽

10.1016/s0022-3468(98)90516-4 ◽

1998 ◽

Vol 33 (7) ◽

pp. 967-972 ◽

Cited By ~ 55

Author(s):

Alan P Ladd ◽

Frederick J Rescorla ◽

Karen W West ◽

L.R Scherer ◽

Scott A Engum ◽

...

Keyword(s):

Necrotizing Enterocolitis ◽

Bowel Resection ◽

Factors Affecting ◽

Long Term Follow Up

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Autoamputation of the Appendix Presenting as a Calcified Abdominal Mass Following Necrotizing Enterocolitis

Pediatric and Developmental Pathology ◽

10.1177/1093526616686256 ◽

2017 ◽

Vol 20 (4) ◽

pp. 335-339 ◽

Cited By ~ 1

Author(s):

Brent R Weil ◽

Alyaa Al-Ibraheemi ◽

Sara O Vargas ◽

Shawn J Rangel

Keyword(s):

Necrotizing Enterocolitis ◽

Bowel Resection ◽

Abdominal Mass ◽

Vermiform Appendix ◽

Male Child ◽

Transverse Mesocolon ◽

Abdominal Radiography ◽

Unusual Event ◽

Pathologic Evaluation ◽

History Of

Autoamputation of the appendix has previously been reported in the literature, but it is likely an unusual event. We report a 2-year-old male child who had previously undergone laparotomy and bowel resection for necrotizing enterocolitis. Two years later a calcified intra-abdominal mass was identified on abdominal radiography and ultrasonography. Eventual laparotomy revealed a densely calcified mass within the transverse mesocolon. The mass was uneventfully resected. Pathologic evaluation showed appendiceal tissue, consistent with prior autoamputation of the vermiform appendix. Autoamputation of the appendix has not to our knowledge previously been associated with a calcified mass nor been associated with a history of necrotizing enterocolitis, and these factors distinguish this case as noteworthy.

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Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00196.2001 ◽

2002 ◽

Vol 282 (1) ◽

pp. G156-G164 ◽

Cited By ~ 178

Author(s):

Bohuslav Dvorak ◽

Melissa D. Halpern ◽

Hana Holubec ◽

Catherine S. Williams ◽

Debra L. McWilliam ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Mrna Expression ◽

Necrotizing Enterocolitis ◽

Rat Model ◽

Transforming Growth Factor ◽

Gastrointestinal Disease ◽

Neonatal Rat ◽

Epidermal Growth ◽

Neonatal Rat Model

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-α mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.

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Intestinal Rehabilitation after Extensive Bowel Resection in Post-Gastrectomy Patients

Surgical Metabolism and Nutrition ◽

10.18858/smn.2015.6.2.33 ◽

2015 ◽

Vol 6 (2) ◽

pp. 33-37

Author(s):

Seung Rim Han ◽

Sanghoon Lee ◽

Chae-Youn Oh ◽

Hyun-Jung Kim ◽

Hyo Jung Park ◽

...

Keyword(s):

Bowel Resection ◽

Intestinal Rehabilitation

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Identification of Inflammatory Genes, Pathways, and Immune Cells in Necrotizing Enterocolitis of Preterm Infant by Bioinformatics Approaches

BioMed Research International ◽

10.1155/2021/5568724 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Lili Zhang ◽

Lizhen Sun ◽

Mingli Wu ◽

Jie Huang

Keyword(s):

Gene Expression ◽

B Cells ◽

Rna Sequencing ◽

Necrotizing Enterocolitis ◽

Immune Cells ◽

Gastrointestinal Disease ◽

Gene Set Enrichment Analysis ◽

High Morbidity ◽

Expression Levels ◽

Gene Expression Levels

Background. Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal disease-causing high morbidity and mortality in premature infants. However, the underlying mechanism of the pathogenesis of NEC is still not fully understood. Methods. RNA sequencing of intestinal specimens from 9 NEC and 5 controls was employed to quantify the gene expression levels. RNA sequencing was employed to quantify the gene expression levels. DESeq2 tool was used to identify the differentially expressed genes. The biological function, pathways, transcription factors, and immune cells dysregulated in NEC were characterized by gene set enrichment analysis. Results. In the present study, we analyzed RNA sequencing data of NECs and controls and revealed that immune-related pathways were highly activated, while some cellular responses to external stimuli-related pathways were inactivated in NEC. Moreover, B cells, macrophages M1, and plasma cells were identified as the major cell types involved in NEC. Furthermore, we also found that inflammation-related transcription factor genes, such as STAT1, STAT2, and IRF2, were significantly activated in NEC, further suggesting that these TFs might play critical roles in NEC pathogenesis. In addition, NEC samples exhibited heterogeneity to some extent. Interestingly, two subgroups in the NEC samples were identified by hierarchical clustering analysis. Notably, B cells, T cells, Th1, and Tregs involved in adaptive immune were predicted to highly infiltrate into subgroup I, while subgroup II was significantly infiltrated by neutrophils. The heterogeneity of immune cells in NEC indicated that both innate and adaptive immunes might induce NEC-related inflammatory response. Conclusions. In summary, we systematically analyzed inflammation-related genes, signaling pathways, and immune cells to characterize the NEC pathogenesis and samples, which greatly improved our understanding of the roles of inflammatory responses in NEC.

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Recent Potential Noninvasive Biomarkers in Necrotizing Enterocolitis

Gastroenterology Research and Practice ◽

10.1155/2019/8413698 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Kewei Wang ◽

Guozhong Tao ◽

Zhen Sun ◽

Karl G. Sylvester

Keyword(s):

Necrotizing Enterocolitis ◽

Very Low Birth Weight ◽

Gastrointestinal Disease ◽

Unmet Need ◽

Preterm Neonates ◽

Diagnostic Biomarkers ◽

The Past ◽

Clinical Associations ◽

Noninvasive Biomarkers ◽

Urine And Serum

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.

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