Defining necrotizing enterocolitis: current difficulties and future opportunities


Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in hospitalized infants. First classified through Bell staging in 1978, a number of additional definitions of NEC have been proposed in the subsequent decades. In this review, we summarize eight current definitions of NEC, and explore similarities and differences in clinical signs and radiographic features included within these definitions, as well as their limitations. We highlight the importance of a global consensus on defining NEC to improve NEC research and outcomes, incorporating input from participants at an international NEC conference. We also highlight the important role of patient-families in helping to redefine NEC.

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Fig. 1: Comparison of risk group, exclusion criteria, and systemic signs across NEC definitions.
Fig. 2: Comparison of intestinal signs and radiologic findings across NEC definitions.


  1. 1.

    Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 187, 1–7 (1978).

    CAS  Article  Google Scholar 

  2. 2.

    Battersby, C., Santhalingam, T., Costeloe, K. & Modi, N. Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review. Arch. Dis. Child Fetal Neonatal Ed. 103, F182–F189 (2018).

    Article  Google Scholar 

  3. 3.

    Walsh, M. C. & Kliegman, R. M. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr. Clin. N. Am. 33, 179–201 (1986).

    CAS  Article  Google Scholar 

  4. 4.

    Stoll, B. J. et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA 314, 1039–1051 (2015).

    CAS  Article  Google Scholar 

  5. 5.

    Walsh, M. C., Kliegman, R. M. & Hack, M. Severity of necrotizing enterocolitis: influence on outcome at 2 years of age. Pediatrics 84, 808–814 (1989).

    CAS  PubMed  Google Scholar 

  6. 6.

    Challis, P. et al. Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study. Acta Paediatr. 108, 835–841 (2019).

    Article  Google Scholar 

  7. 7.

    Gordon, P. V., Clark, R., Swanson, J. R. & Spitzer, A. Can a national dataset generate a nomogram for necrotizing enterocolitis onset? J. Perinatol. 34, 732–735 (2014).

    CAS  Article  Google Scholar 

  8. 8.

    Aschner, J. L., Deluga, K. S., Metlay, L. A., Emmens, R. W. & Hendricks-Munoz, K. D. Spontaneous focal gastrointestinal perforation in very low birth weight infants. J. Pediatr. 113, 364–367 (1988).

    CAS  Article  Google Scholar 

  9. 9.

    Gordon, P. V. Understanding intestinal vulnerability to perforation in the extremely low birth weight infant. Pediatr. Res. 65, 138–144 (2009).

    Article  Google Scholar 

  10. 10.

    Wadhawan, R. et al. Spontaneous intestinal perforation in extremely low birth weight infants: association with indometacin therapy and effects on neurodevelopmental outcomes at 18–22 months corrected age. Arch. Dis. Child Fetal Neonatal Ed. 98, F127–F132 (2013).

    Article  Google Scholar 

  11. 11.

    Ng, P. C. et al. Comparative miRNA expressional profiles and molecular networks in human small bowel tissues of necrotizing enterocolitis and spontaneous intestinal perforation. PLoS ONE 10, e0135737 (2015).

    Article  Google Scholar 

  12. 12.

    Gordon, P. V., Swanson, J. R., Attridge, J. T. & Clark, R. Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell’s criteria? J. Perinatol. 27, 661–671 (2007).

    CAS  Article  Google Scholar 

  13. 13.

    Juhl, S. M., Hansen, M. L., Gormsen, M., Skov, T. & Greisen, G. Staging of necrotising enterocolitis by Bell’s criteria is supported by a statistical pattern analysis of clinical and radiological variables. Acta Paediatr. 108, 842–848 (2019).

    Article  Google Scholar 

  14. 14.

    Di Napoli, A. et al. Inter-observer reliability of radiological signs of necrotising enterocolitis in a population of high-risk newborns. Paediatr. Perinat. Epidemiol. 18, 80–87 (2004).

    Article  Google Scholar 

  15. 15.

    Rehan, V. K. et al. Observer variability in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis. Clin. Pediatr. (Philos.). 38, 637–643 (1999).

    CAS  Article  Google Scholar 

  16. 16.

    Vermont Oxford Network. (2019).

  17. 17.

    Vermont Oxford Network. 2019 Manual of operations, Part 2, release 23.2. (2019).

  18. 18.

    Horbar, J. D. et al. Variation in performance of neonatal intensive care units in the United States. JAMA Pediatr. 171, e164396 (2017).

    Article  Google Scholar 

  19. 19.

    Centers for Disease Control and Prevention. CDC/NHSN surveillance definitions for specific types of infections. (2019).

  20. 20.

    Battersby, C., Longford, N., Costeloe, K. & Modi, N., Group UKNCNES. Development of a gestational age-specific case definition for neonatal necrotizing enterocolitis. JAMA Pediatr. 171, 256–263 (2017).

    Article  Google Scholar 

  21. 21.

    Battersby, C., Longford, N., Mandalia, S., Costeloe, K. & Modi, N., Group UKNCNEs. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012–13: a whole-population surveillance study. Lancet Gastroenterol. Hepatol. 2, 43–51 (2017).

    Article  Google Scholar 

  22. 22.

    Gephart, S. M. et al. Changing the paradigm of defining, detecting, and diagnosing NEC: perspectives on Bell’s stages and biomarkers for NEC. Semin. Pediatr. Surg. 27, 3–10 (2018).

    Article  Google Scholar 

  23. 23.

    Gordon, P. V., Swanson, J. R., MacQueen, B. C. & Christensen, R. D. A critical question for NEC researchers: can we create a consensus definition of NEC that facilitates research progress? Semin. Perinatol. 41, 7–14 (2017).

    Article  Google Scholar 

  24. 24.

    Ji, J. et al. A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis. PLoS ONE 9, e89860 (2014).

    Article  Google Scholar 

  25. 25.

    Caplan, M. S. et al. Necrotizing enterocolitis: using regulatory science and drug development to improve outcomes. J. Pediatr. 212, 208–215.e1 (2019).

    Article  Google Scholar 

  26. 26.

    Kane, A. F., Bhatia, A. D., Denning, P. W., Shane, A. L. & Patel, R. M. Routine supplementation of Lactobacillus rhamnosus GG and risk of necrotizing enterocolitis in very low birth weight infants. J. Pediatr. 195, 73–9 e2 (2018).

    Article  Google Scholar 

  27. 27.

    van Druten, J., Khashu, M., Chan, S. S., Sharif, S. & Abdalla H. Abdominal ultrasound should become part of standard care for early diagnosis and management of necrotising enterocolitis: a narrative review. Arch. Dis. Child Fetal Neonatal Ed. 104, F551–F559 (2019).

    Article  Google Scholar 

  28. 28.

    Cuna, A. C. et al. Bowel ultrasound for the diagnosis of necrotizing enterocolitis: a meta-analysis. Ultrasound Q. 34, 113–118 (2018).

    PubMed  Google Scholar 

  29. 29.

    Janssen Lok, M. et al. Value of abdominal ultrasound in management of necrotizing enterocolitis: a systematic review and meta-analysis. Pediatr. Surg. Int. 34, 589–612 (2018).

    Article  Google Scholar 

  30. 30.

    Ng, P. C. An update on biomarkers of necrotizing enterocolitis. Semin. Fetal Neonatal Med. 23, 380–386 (2018).

    Article  Google Scholar 

  31. 31.

    Brown, J. V. E., Meader, N., Cleminson, J. & McGuire, W. C-reactive protein for diagnosing late-onset infection in newborn infants. Cochrane Database Syst. Rev. 1, CD012126 (2019).

    PubMed  Google Scholar 

  32. 32.

    Hornik, C. P. et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr. Infect. Dis. J. 31, 799–802 (2012).

    Article  Google Scholar 

  33. 33.

    Rajkomar, A., Dean, J. & Kohane, I. Machine learning in medicine. N. Engl. J. Med. 380, 1347–1358 (2019).

    Article  Google Scholar 

  34. 34.

    Irles, C. et al. Estimation of neonatal intestinal perforation associated with necrotizing enterocolitis by machine learning reveals new key factors. Int. J. Environ. Res. Public Health 15, 2509 (2018).

    CAS  Article  Google Scholar 

  35. 35.

    The Infant Journal. SIGNEC Sixth International Conference on Necrotising Enterocolitis. (2019).

  36. 36.

    Inspire. NEC Society connects: necrotizing enterocolitis support group and discussion community. (2019).

  37. 37.

    Jensen, E. A. et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach. Am. J. Respir. Crit. Care Med. 200, 751–759 (2019).

    CAS  Article  Google Scholar 

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R.M.P. received funding from the NIH under awards: KL2 TR000455, UL1 TR000454, and K23 HL128942. The NIH had no role in: (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Publication of this article was sponsored by the Necrotizing Enterocolitis (NEC) Society, Patient-Centered Outcomes Research Institute, and National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development under award number R13 HD098853.

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R.M.P., J.F., S.J.M., M.K., and M.S.C. all made substantial contributions to conception of the article, drafting the article, critical revisions, and approve of the final version to be published.

Corresponding author

Correspondence to Ravi Mangal Patel.

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Competing interests

R.M.P. has received honoraria and travel support from Mednax, Inc., partial travel support from Danone Nutricia to attend a meeting, and consulted for Shipman & Goodwin, LLP and serves on the data-monitoring committee of the Connection Study conducted by Premier Research/Infant Bacterial Therapeutics. None of these entities had any role in this manuscript. S.J.M. received lecture fees from Abbott, grant support from Evolve Biosystems and the Carver College of Medicine at the University of Iowa for unrelated work. M.K. received an educational grant from Danone Nutricia to organize a conference on NEC. M.S.C. received consulting fees from Sigma Tau Pharmaceuticals and lecture fees from Mead Johnson Nutrition. The remaining authors declare no competing interests.

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The Emory University Institutional Review board evaluated the audience response questions and deemed this to not be human subjects research.

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Patel, R.M., Ferguson, J., McElroy, S.J. et al. Defining necrotizing enterocolitis: current difficulties and future opportunities. Pediatr Res 88, 10–15 (2020).

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