Effect of Necrotizing Enterocolitis on Growth and Development in Preterm Neonates

  • Sanjay Patole
  • Girish Deshpande


Necrotizing enterocolitis (NEC) is a potentially disastrous illness in preterm neonates with significant mortality and morbidity including need for surgery, prolonged dependence on parenteral nutrition, and survival with short bowel syndrome and its consequences. The incidence of NEC has not changed significantly despite the recent advances in neonatal intensive care. However, the improved standard of care means the absolute number of survivors of NEC has increased. Long-term growth and neurodevelopmental impairment in preterm, especially extremely low birth weight, neonates needing surgery for the illness is a significant issue. Systematic reviews of observational studies indicate that the risk of long-term neurodevelopmental impairment (NDI) is significantly higher in preterm very low birth weight (VLBW) neonates with ≥ Bell Stage II NEC vs no NEC (OR: 1.82; 95% CI: 1.46–2.27), and those requiring surgery are at a higher risk for NDI vs those managed medically (OR: 1.99; 95% CI: 1.26–3.14). Inflammatory cytokines like tumor necrosis factor alpha and platelet activating factor play an important role in the pathogenesis of NEC and sepsis, which are often associated with each other. Prolonged exposure of an immature and vulnerable brain to high levels of inflammatory cytokines, recurrent bouts of sepsis, and suboptimal nutrition during the critical early postnatal period explain the adverse effects on growth and neurodevelopment in survivors of surgical NEC. Despite decades of research the pathogenesis of NEC continues to remain poorly understood. Prevention of prematurity, the single most important risk factor for the illness, is difficult. However, antenatal glucocorticoids and preferential feeding with breast milk have been consistently shown to reduce the risk of NEC significantly. Prophylactic probiotic supplementation also significantly reduces the risk of NEC and all-cause mortality while facilitating feed tolerance in preterm VLBW neonates. Secondary prevention is equally important as almost all of the morbidity including long-term impairment of growth and neurodevelopment is faced by those in whom NEC progresses to a stage needing surgery. Early diagnosis, prompt surgical intervention, and an aggressive approach to management of sepsis and provision of optimal nutrition may minimize the adverse effects of NEC on growth and neurodevelopment of preterm neonates.


Short Bowel Syndrome Preterm Neonate Pneumatosis Intestinalis Neurodevelopmental Impairment Psychomotor Development Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Abdominal ultrasound


Confidence interval


Extremely low birth weight


Laparotomy with bowel resection




Medically managed NEC


Magnetic resonance imaging


Neurodevelopmental impairment


Necrotizing enterocolitis


Odds ratio


Platelet activating factor


Pneumatosis intestinalis


Primary peritoneal drainage


Periventricular leukomalacia


Surgically managed NEC


Tumor necrosis factor alpha


Total parenteral nutrition


Very low birth weight


White matter abnormality


  1. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.PubMedCrossRefGoogle Scholar
  2. Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics. 2002;109:423–8.PubMedCrossRefGoogle Scholar
  3. Bohnhorst B, Muller S, Dordelmann M, Peter CS, Petersen C, Poets CF. Early feeding after necrotizing enterocolitis in preterm infants. J Pediatr. 2003;143:484–7.PubMedCrossRefGoogle Scholar
  4. Cakir M, Mungan I, Karahan C, Can G, Okten A. Necrotizing enterocolitis increases the bone resorption in premature infants. Early Hum Dev. 2006;82:405–9.PubMedCrossRefGoogle Scholar
  5. Caplan MS, Sun XM, Hseuh W, Hageman JR. Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr. 1990;116:960–4.PubMedCrossRefGoogle Scholar
  6. Catlin A. Extremely long hospitalizations of newborns in the United States: data, descriptions, dilemmas. J Perinatol. 2006;26:742–8.PubMedCrossRefGoogle Scholar
  7. Cooke RJ, Ainsworth SB, Fenton AC. Postnatal growth retardation: a universal problem in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2004;89: F428–30.PubMedCrossRefGoogle Scholar
  8. Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet 2007;369:1614–20.PubMedCrossRefGoogle Scholar
  9. di Napoli A, Di Lallo D, Perucci CA, Schifano P, Orzalesi M, Franco F, De Carolis MP. Inter-observer reliability of radiological signs of necrotising enterocolitis in a population of high-risk newborns. Paediatr Perinat Epidemiol. 2004;18:80–7.PubMedCrossRefGoogle Scholar
  10. Doyle LW, Callanan C, Carse E, Charlton M, Drew J, Ford G. The Victorian Infant Collaborative Study Group. Surgery and the tiny baby: sensorineural outcome at 5 years of age. J Paediatr Child Health. 1996;32:167–72.CrossRefGoogle Scholar
  11. Flake AW. Necrotizing enterocolitis in preterm infants – is laparotomy necessary? N Engl J Med. 2006;354:2275–6.PubMedCrossRefGoogle Scholar
  12. Flidel-Rimon O, Blanski D, Shinwell ES. The fear of necrotizing enterocolitis versus achieving optimal growth in preterm infants – an opinion. Acta Pediatr. 2006;95:1341–4.CrossRefGoogle Scholar
  13. Haque K, Mohan P. Pentoxifylline for neonatal sepsis. Cochrane Database Syst Rev. 2003;CD004205.Google Scholar
  14. Harris MC, D’Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L. Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing enterocolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr. 2005;147:462–8.PubMedCrossRefGoogle Scholar
  15. Henry MC, Moss RL. Necrotising enterocolitis. Semin Pediatr Surg. 2008;17:98–109.PubMedCrossRefGoogle Scholar
  16. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005;115:696–703.PubMedCrossRefGoogle Scholar
  17. Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CL, Schonberger LB. Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol. 2006;20:498–506.PubMedCrossRefGoogle Scholar
  18. Hsueh W, Caplan MS, Sun X, Tan X, MacKendrick W, Gonzalez-Crussi F. Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis. Acta Paediatr. 1994;Suppl 396:11–17.CrossRefGoogle Scholar
  19. Hsueh W, Caplan MS, Qu XW, Tan XD, DePlaen IG, Gonzalez-Crussi F. Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr Dev Pathol. 2003;6:6–23.PubMedCrossRefGoogle Scholar
  20. Kim WY, Kim WS, Kim IO, Kwon TH, Chang W, Lee EK. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr Radiol. 2005;35:1056–61.PubMedCrossRefGoogle Scholar
  21. Kliegman RM, Fanaroff AA. Neonatal necrotising enterocolitis in the absence of pneumatosis intestinalis. Am J Dis Child. 1982;136:618–20.PubMedGoogle Scholar
  22. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet 2006;368:1271–83.PubMedCrossRefGoogle Scholar
  23. Lodha AK. Cytokine levels in neonatal necrotizing enterocolitis and long-term growth and neurodevelopment. Acta Paediatr. 2010;99:338–43.PubMedCrossRefGoogle Scholar
  24. Morris BH, Landry SH, Smith KE, Swank PR, Denson SE. Feeding, medical factors, and developmental outcome in premature infants. Clin Pediatr. 1999;38:451–7.CrossRefGoogle Scholar
  25. Moss RL, Dimmitt RA, Barnhart DC, Sylvester KG, Brown RL, Powell DM, Islam S, Langer JC, Sato TT, Brandt ML, Lee H, Blakely ML, Lazar EL, Hirschl RB, Kenney BD, Hackam DJ, Zelterman D, Silverman BL. Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation. N Engl J Med. 2006;354:2225–34.PubMedCrossRefGoogle Scholar
  26. Ni Choileain NN, Redmond HP. Cell response to surgery. Arch Surg. 2006;141:1132–40.PubMedCrossRefGoogle Scholar
  27. Obladen M. Necrotising enterocolitis: 150 years of fruitless search for the causes. Neonatology 2009;96:203–10.PubMedCrossRefGoogle Scholar
  28. Patole SK. Prevention of necrotising enterocolitis-Year 2004 and beyond. J Matern Fetal Neonatal Med. 2005a;17:69–80.PubMedCrossRefGoogle Scholar
  29. Patole S. Prevention of necrotising enterocolitis-Year 2004 and beyond. J Matern Fetal Neonatal Med. 2005b;18:67–76.PubMedCrossRefGoogle Scholar
  30. Petrosyan M, Guner YS, Williams M, Grishin A, Ford HR. Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr Surg Int. 2009;25:309–18.PubMedCrossRefGoogle Scholar
  31. Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007;92:F193–8.PubMedCrossRefGoogle Scholar
  32. Rees CM, Eaton S, Kiely EM, Wade AM, McHugh K, Pierro A. Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial. Ann Surg. 2008;248:44–51.PubMedCrossRefGoogle Scholar
  33. Rowe MI, Reblock KK, Kurkchubasche AG, Healey PJ. Necrotizing enterocolitis in the extremely low birth weight infant. J Pediatr Surg. 1994;29:987–90; discussion 990–1.PubMedCrossRefGoogle Scholar
  34. Schulzke S, Deshpande GC, Patole SK. Neurodevelopmental outcome of very low birth weight infants with necrotizing enterocolitis – a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007;161:583–90.PubMedCrossRefGoogle Scholar
  35. Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW, Inder TE. Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term. J Pediatr. 2008;153:170–5.PubMedCrossRefGoogle Scholar
  36. Soraisham AS, Amin HJ, Al-Hindi MY, Singhal N, Sauve RS. Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight b or =1250 g? J Pediatr Child Health. 2006;42:499–504.CrossRefGoogle Scholar
  37. Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004;292:2357–65.PubMedCrossRefGoogle Scholar
  38. Tan HL, Tantoco JG, Ee MZ. The role of diagnostic laparoscopy in micropremees with suspected necrotizing enterocolitis. Surg Endosc. 2007;21:485.PubMedCrossRefGoogle Scholar
  39. Travadi J, Patole S, Charles A, Doherty D, Dvorak B, Simmer K. Pentoxifylline reduces the incidence of necrotising enterocolitis in a neonatal rat model. Pediatr Res. 2006;60:185–9.PubMedCrossRefGoogle Scholar
  40. Volpe JJ. Postnatal sepsis, necrotizing enterocolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J Pediatr. 2008;153:160–3.PubMedCrossRefGoogle Scholar
  41. Wamer BW, Falcone RA. Images in clinical medicine: pneumatosis intestinalis. J Pediatr. 2003;143:543.CrossRefGoogle Scholar
  42. Young C, Sharma R, Handfield M, Mai V, Neu J. Biomarkers for infants at risk for necrotizing enterocolitis: clues to prevention? Pediatr Res. 2009;65:91–7.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.King Edward Memorial Hospital for Women, Centre for Neonatal Research and Education, University of Western AustraliaSubiacoAustralia
  2. 2.King Edward Memorial Hospital for WomenSubiacoAustralia

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