Necrotizing Enterocolitis in Premature Infants

Introduction and Epidemiology

Necrotizing enterocolitis (NEC), occurring in 1 to 3 per 1000 live births, is the most common gastrointestinal emergency in preterm infants with a mortality of 30-50%.^1-2 The disorder is characterised by a constellation of events including: ischemia of the intestinal mucosa, followed by inflammation, invasion of various enteric gas forming organisms, and leakage of gas into the intestinal muscularis and portal venous system.¹

The pathological process occurring in NEC is mainly attributable to intestinal infarction of the terminal ileum or colon, however, in severe cases the whole gastrointestinal tract can be affected.^3-4 Over time as the gastrointestinal tract heals, the bowel wall thickens forming fibrinous adhesions leading to stenosis.³ This multifactorial disease has various risk factors including: prematurity, overgrowth of microorganisms, impaired defences of the mucosa, and formula feeding.³

Clinical Presentation and Diagnosis

A challenge arises amongst clinicians to adequately diagnose NEC in the earliest stages, as the clinical presentation varies.⁵ The Modified Bell’s Staging Criteria (Figure 1) incorporates systemic, intestinal, and radiological signs to adequately diagnose, stage, and treat NEC.^2,5-6 Various signs and symptoms are exhibited, such as: bilious vomit, diarrhea, distended abdomen, lethargy, and abnormal vitals (temperature instability and bradycardia).^6,7 Laboratory investigations can support the diagnosis, such as: alterations in white blood cell count, thrombocytopenia, metabolic acidosis and hyperglycemia.^1,7 Additionally, a septic workup is performed when any signs or symptoms of sepsis is suspected.⁷ Plain film abdominal radiographs exhibit the pathognomonic, Pneumatosis intestinalis, indicating the presence of gas in the bowel wall originating from various pathogenic bacteria.^2,8

Figure 1: Bells Staging Criteria using systemic, intestinal and radiological signs used in the diagnosis and staging of Necrotizing Enterocolitis.^2,6

Management

Management of NEC depends on the stage of the disease. Infants with Bell’s Stage I or II are managed medically, with interventions including: bowel rest by withholding feeds and use of parental nutrition, ventilatory support, fluid resuscitation, electrolyte correction, acid-base correction and antibiotic administration.² Unfortunately, there is no consensus on which antibiotics should be used and is based on institutional protocol and culture and sensitivity results.²

In neonates with more advanced staging, deteriorating disease or intestinal perforation, acute surgical intervention can be implicated.^2,9-10 As laparotomy in neonates with advanced disease results in serious morbidity or mortality, percutaneous insertion of a peritoneal drain delays the use of laparotomy.¹⁰ Peritoneal drainage consists of: irrigation of the peritoneal cavity with saline, peritoneal fluid cultures and sensitivity, and placement of a Penrose drain over the abdomen.⁹

In regard to surgical treatment of NEC, the universally accepted consensus is to remove the necrotic intestine and treat intra-abdominal sepsis.² Classically, NEC is surgically managed by surgical resection of the necrotic intestine and placement of a stoma to allow the loops of bowel to heel and grow until a later stage in the infant’s life.¹⁰ However, stomas are poorly tolerated by preterm infants and predispose them to nutritional, electrolyte, and fluid abnormalities.² Alternatively, some surgeons prefer bowel resection and primary anastomosis.¹⁰ Short term complications of surgery include, NEC related mortality, anastomotic leak and short bowel syndrome.²

Complications

Various complications arise in NEC survivors, especially in neonates with advanced staging (Stage III) or in neonates requiring surgical intervention. These complications include neurodevelopmental impairment, compromised growth and decreased cognitive outcomes.¹¹ Additionally, multiple cohort studies show that NEC increases the requirement for prolonged intubation, sepsis, increased hospitalization, peri-ventricular leukomalacia and chronic lung disease.¹¹

As substantial financial burdens and reduced quality of life for the patient and the families and are experienced, preventative strategies are required in the management of NEC.² Efforts to reduce the incidence of NEC include reducing exposure to various risk factors and encouraging use of human milk.¹² Additional preventative measures includes use of: early recognition of NEC signs and symptoms, histamine 2 blockers, and antibiotics.¹²

References

1. Schanler RJ, Abrams SA, Kim MS. Clinical features and diagnosis of necrotizing enterocolitis in newborns [Internet]. 2016 Nov [cited 2017 Dec 28]. Available from: https://www-uptodate-com.proxy.library.rcsi.ie/contents/clinical-features-and-diagnosis-of-necrotizing-enterocolitis-in-newborns?search=necrotizing%20enterocolitis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
2. Zani A, Pierro A. Necrotizing enterocolitis: controversies and challenges [Internet]. 2015 Nov [cited 2017 Dec 28]. 4(F100 Faculty Rev):1373. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753995/
3. Schanler RJ, Abrams SA, Kim MS. Pathology and pathogenesis of necrotizing enterocolitis in newborns [Internet]. Nov 2016 [cited 2017 Dec 28]. Available from: https://www-uptodate-com.proxy.library.rcsi.ie/contents/pathology-and-pathogenesis-of-necrotizing-enterocolitis-in-newborns?source=see_link
4. Ballance WA, Dahms BB, Shenker N, Kligman RM. Pathology of neonatal necrotizing enterocolitis: a ten-year experience [Internet]. 1990 July [cited 2017 Dec 28]; 117 (1 Pt 2): S6-13). Available from: https://www-ncbi-nlm-nih-gov.proxy.library.rcsi.ie/pubmed?term=2362230
5. Gregory KE, DeForge CE, Natale KM, Phillips M, Van Marter LJ. Necrotizing enterocolitis in the premature infant [Internet]. 2011 June [cited 2017 Dec 28]; 11(3):155-166. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759524/
6. Franklin AL, Cappiello CD, Gordish- Dressman H, Tatari-Calderone Z, Vukmanovic S, Rais-Bahrami K, et al. Are immune modulating single nuceloride polymorphisms associated with necrotizing enterocolitis [Internet]? 2015 Dec [cited 2017 Dec 28]. Available from: https://www.nature.com/articles/srep18369#t1
7. Seattle Children’s Hospital. Digestive and gastrointestinal conditions: necrotizing enterocolitis [Internet]. (undated) Available from: http://www.seattlechildrens.org/medical-conditions/digestive-gastrointestinal-conditions/necrotizing-enterocolitis-symptoms/
8. Esposito F, Mamone R, Di Serafino M, Mercogliano C, Vitale V, Vallone G, et al. Diagnostic imaging features of necrotizing enterocolitis: a narrative review [Internet]. 2017 June [cited 2017 Dec 28]; 7(3):336-344. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537125/
9. Schanler RJ, Abrams SA, Kim MS. Management of necrotizing enterocolitis [Internet]. 2017 Nov [cited 2017 Dec 28]. Available from: https://www-uptodate-com.proxy.library.rcsi.ie/contents/management-of-necrotizing-enterocolitis-in-newborns?search=necrotizing%20enterocolitis&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H7
10. Thakkar HS, Lakhoo K. The surgical management of necrotising enterocolitis (NEC) [Internet]. 2016 Jun [cited 2017 Dec 28]; 97:25-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27032753
11. Arnold M, Moore SW, Silder D, Kirsten GF. Long-term outcome of surgically managed necrotizing enterocolitis in a developing country [Internet]. 2010 March [cited 2017 Dec 28]; 26:355-360. Available from: https://www.researchgate.net/publication/41762136_Long-term_outcome_of_surgically_managed_necrotizing_enterocolitis_in_a_developing_country
12. Schanler RJ, Abrams SA, Kim MS. Prevention of necrotizing enterocolitis in newborns [Internet]. 2017 Nov [cited 2017 Dec 28]. Available from: https://www-uptodate-com.proxy.library.rcsi.ie/contents/prevention-of-necrotizing-enterocolitis-in-newborns?search=necrotizing%20enterocolitis&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5#H9