Skip to main content

Effect of Necrotizing Enterocolitis on Growth and Development in Preterm Neonates

  • Chapter
  • First Online:
Handbook of Growth and Growth Monitoring in Health and Disease

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AUS:

Abdominal ultrasound

CI:

Confidence interval

ELBW:

Extremely low birth weight

LBR:

Laparotomy with bowel resection

LPS:

Lipopolysaccharide

MedNEC:

Medically managed NEC

MRI:

Magnetic resonance imaging

NDI:

Neurodevelopmental impairment

NEC:

Necrotizing enterocolitis

OR:

Odds ratio

PAF:

Platelet activating factor

PI:

Pneumatosis intestinalis

PPD:

Primary peritoneal drainage

PVL:

Periventricular leukomalacia

SurgNEC:

Surgically managed NEC

TNF-α:

Tumor necrosis factor alpha

TPN:

Total parenteral nutrition

VLBW:

Very low birth weight

WMA:

White matter abnormality

References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Catlin A. Extremely long hospitalizations of newborns in the United States: data, descriptions, dilemmas. J Perinatol. 2006;26:742–8.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Flake AW. Necrotizing enterocolitis in preterm infants – is laparotomy necessary? N Engl J Med. 2006;354:2275–6.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Haque K, Mohan P. Pentoxifylline for neonatal sepsis. Cochrane Database Syst Rev. 2003;CD004205.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Henry MC, Moss RL. Necrotising enterocolitis. Semin Pediatr Surg. 2008;17:98–109.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Kliegman RM, Fanaroff AA. Neonatal necrotising enterocolitis in the absence of pneumatosis intestinalis. Am J Dis Child. 1982;136:618–20.

    PubMed  CAS  Google Scholar 

  • Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet 2006;368:1271–83.

    Article  PubMed  Google Scholar 

  • Lodha AK. Cytokine levels in neonatal necrotizing enterocolitis and long-term growth and neurodevelopment. Acta Paediatr. 2010;99:338–43.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Ni Choileain NN, Redmond HP. Cell response to surgery. Arch Surg. 2006;141:1132–40.

    Article  PubMed  Google Scholar 

  • Obladen M. Necrotising enterocolitis: 150 years of fruitless search for the causes. Neonatology 2009;96:203–10.

    Article  PubMed  Google Scholar 

  • Patole SK. Prevention of necrotising enterocolitis-Year 2004 and beyond. J Matern Fetal Neonatal Med. 2005a;17:69–80.

    Article  PubMed  Google Scholar 

  • Patole S. Prevention of necrotising enterocolitis-Year 2004 and beyond. J Matern Fetal Neonatal Med. 2005b;18:67–76.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Tan HL, Tantoco JG, Ee MZ. The role of diagnostic laparoscopy in micropremees with suspected necrotizing enterocolitis. Surg Endosc. 2007;21:485.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Wamer BW, Falcone RA. Images in clinical medicine: pneumatosis intestinalis. J Pediatr. 2003;143:543.

    Article  Google Scholar 

  • 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sanjay Patole .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Patole, S., Deshpande, G. (2012). Effect of Necrotizing Enterocolitis on Growth and Development in Preterm Neonates. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1795-9_33

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1794-2

  • Online ISBN: 978-1-4419-1795-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics