Skip to main content

Prevention and Treatment of Necrotising Enterocolitis in Preterm Neonates

  • Chapter
  • First Online:
Nutrition for the Preterm Neonate

Abstract

Necrotising enterocolitis (NEC) is a potentially disastrous illness in preterm, especially extremely preterm (gestation under 28 weeks) neonates with significant mortality, and morbidity including long term neurodevelopmental impairment. With improved survival of neonates at the limits of viability, the size of the population at risk for NEC has increased in recent years. NEC is a common cause of death in preterm neonates who survive the first week of life. The estimated annual economic burden related to NEC is close a billion dollar in the USA. Prevention and treatment of NEC has thus become a priority. Recent research has improved the understanding of the role of innate immunity in the pathogenesis of NEC. As new frontiers like probiotics and lactoferrin continue to be explored, the impact of well-established simple strategies like antenatal glucocorticoid therapy, and early and preferential use of breast milk should not be forgotten for primary prevention of NEC. Clinical research is needed on feed intolerance, safety of minimal enteral feeds in terms of NEC, and benefits of standardised feeding regimens. Association of common clinical practices such as red cell transfusions, H2 receptor blockade, undue prolonged antibiotic treatment, and thickening of feeds with NEC also warrants attention. Evaluating potential strategies for secondary prophylaxis (e.g., pentoxifylline) is equally important considering the fact that almost the entire health burden of NEC is related to progression of the illness from Stage II to Stage III. A package of potentially better practices seems to be the most appropriate strategy for the prevention and treatment of NEC.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Similar content being viewed by others

References

  1. Neu J, Walker WA (2011) Necrotizing enterocolitis. N Engl J Med 364:255–264

    PubMed  CAS  Google Scholar 

  2. Berman L, Moss RL (2011) Necrotizing enterocolitis: an update. Semin Fetal Neonatal Med 16:145–150

    PubMed  Google Scholar 

  3. Rowe MI, Reblock KK, Kurkchubasche AG, Healey PJ (1994) Necrotizing enterocolitis in the extremely low birth weight infant. J Pediatr Surg 29:987–990

    PubMed  CAS  Google Scholar 

  4. Schulzke SM, Deshpande GC, Patole SK (2007) Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med 161:583–590

    PubMed  Google Scholar 

  5. Bisquera JA, Cooper TR, Berseth CL (2002) Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics 109:423–428

    PubMed  Google Scholar 

  6. Schnabl KL, Van Aerde JE, Thomson AB, Clandinin MT (2008) Necrotizing enterocolitis: a multifactorial disease with no cure. World J Gastroenterol 14:2142–2161

    PubMed  CAS  Google Scholar 

  7. Obladen M (2009) Necrotizing enterocolitis—150 years of fruitless search for the cause. Neonatol 96:203–210

    Google Scholar 

  8. Van Marter LJ, Dammann O, Allred EN, Leviton A, Pagano M, Moore M, Martin C (2002) Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 140:171–176

    PubMed  Google Scholar 

  9. Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R, Llanos A, Claud EC, Walker WA (2011) The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS ONE 6(3):e17776

    PubMed  CAS  Google Scholar 

  10. Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ (2004) Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci USA 101:7404–7408

    PubMed  CAS  Google Scholar 

  11. Morgan JA, Young L, McGuire W (2011) Pathogenesis and prevention of necrotizing enterocolitis. Curr Opin Infect Dis 24:183–189

    PubMed  Google Scholar 

  12. Lu J, Caplan MS, Saraf AP, Li D, Adler L, Liu X, Jilling T (2004) Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 286:G340–G350

    PubMed  CAS  Google Scholar 

  13. Lu J, Caplan MS, Li D, Jilling T (2008) Polyunsaturated fatty acids block platelet-activating factor-induced phosphatidylinositol 3 kinase/Akt-mediated apoptosis in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 294:G1181–G1190

    PubMed  CAS  Google Scholar 

  14. Claud EC, Lu J, Wang XQ, Abe M, Petrof EO, Sun J, Nelson DJ, Marks J, Jilling T (2008) Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 294:G1191–G1200

    PubMed  CAS  Google Scholar 

  15. Caplan MS, Sun XM, Hseuh W, Hageman JR (1990) Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr 116:960–964

    PubMed  CAS  Google Scholar 

  16. Morecroft JA, Spitz L, Hamilton PA, Holmes SJ (1994) Plasma cytokine levels in necrotizing enterocolitis. Acta Paediatr Suppl 396:18–20

    PubMed  CAS  Google Scholar 

  17. Morecroft JA, Spitz L, Hamilton PA, Holmes SJ (1994) Plasma interleukin-6 and tumour necrosis factor levels as predictors of disease severity and outcome in necrotizing enterocolitis. J Pediatr Surg 29:798–800

    PubMed  CAS  Google Scholar 

  18. Fitzgibbons SC, Ching Y, Yu D, Carpenter J, Kenny M, Weldon C, Lillehei C, Valim C, Horbar JD, Jaksic T (2009) Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 44:1072–1075 (discussion 1075–1076)

    Google Scholar 

  19. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045–1049

    PubMed  CAS  Google Scholar 

  20. Djeu JY, Matsushima K, Oppenheim JJ, Shiotsuki K, Blanchard DK (1990) Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. J Immunol 144:2205–2210

    PubMed  CAS  Google Scholar 

  21. Huber AR, Kunkel SL, Todd RF 3rd, Weiss SJ (1991) Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science 254:99–102

    PubMed  CAS  Google Scholar 

  22. Edelson MB, Bagwell CE, Rozycki HJ (1999) Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis. Pediatrics 103:766–771

    PubMed  CAS  Google Scholar 

  23. Nadler EP, Stanford A, Zhang XR, Schall LC, Alber SM, Watkins SC, Ford HR (2001) Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease. J Pediatr Surg 36:1122–1129

    PubMed  CAS  Google Scholar 

  24. Emami CN, Chokshi N, Wang J, Hunter C, Guner Y, Goth K, Wang L, Grishin A, Ford HR (2012) Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis. Am J Surg 203:428–435

    PubMed  CAS  Google Scholar 

  25. Fituch CC, Palkowetz KH, Goldman AS, Schanler RJ (2004) Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis. Acta Paediatr 93:1496–1500

    PubMed  CAS  Google Scholar 

  26. Fuller R (1991) Probiotics in human medicine. Gut 32:439–442

    PubMed  CAS  Google Scholar 

  27. Claud EC, Walker WA (2008) Bacterial colonization, probiotics, and necrotizing enterocolitis. J Clin Gastroenterol 42:S46–S52

    PubMed  Google Scholar 

  28. Walker WA (2008) Mechanisms of action of probiotics. Clin Infect Dis 46:S87–S91 (discussion S144–S151)

    Google Scholar 

  29. Martin CR, Walker WA (2008) Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis. Semin Perinatol 32:127–137

    PubMed  Google Scholar 

  30. Boirivant M, Strober W (2007) The mechanism of action of probiotics. Curr Opin Gastroen 23:679–692

    Google Scholar 

  31. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F et al (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229–241

    PubMed  CAS  Google Scholar 

  32. Ewaschuk JB, Blacker JL, Churchill TA et al (2007) Surface expression of Toll-like receptor 9 is upregulated on intestinal epithelial cells in response to pathogenic bacterial DNA. Infect Immun 75:2572–2579

    PubMed  CAS  Google Scholar 

  33. Veckman V, Miettinen M, Pirhonen J et al (2004) Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of TH1-type cytokines and chemokines in human monocyte-derived dendritic cells. J Leukoc Biol 75:764–771

    PubMed  CAS  Google Scholar 

  34. Lavasani S, Dzhambazov B, Nouri M et al (2010) A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS ONE 5:e9009

    PubMed  Google Scholar 

  35. O’Donovan DJ, Fernandes CJ (2004) Free radicals and diseases in premature infants. Antioxid Redox Signal 6:169–176

    PubMed  Google Scholar 

  36. Baker RD, Baker SS, LaRosa K (1995) Polarized Caco-2 cells. Effect of reactive oxygen metabolites on enterocyte barrier function. Dig Dis Sci 40:510–518

    CAS  Google Scholar 

  37. Clark DA, Fornabaio DM, McNeill H, Mullane KM, Caravella SJ, Miller MJ (1988) Contribution of oxygen-derived free radicals to experimental necrotizing enterocolitis. Am J Pathol 130:537–542

    PubMed  CAS  Google Scholar 

  38. Sheth PS, Basuroy S, Li C, Naren AP, Rao RK (2003) Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. J Biol Chem 278:49239–49245

    PubMed  CAS  Google Scholar 

  39. Rao RK, Polk DB, Seth A, Yan F (2009) Probiotics the good neighbour: guarding the gut mucosal barrier. Am J Infect Dis 5:188–192

    Google Scholar 

  40. Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R (2009) Effect of probiotic and prebiotic on gastrointestinal motility in newborns. J Physiol Pharmacol 60:S27–S31

    Google Scholar 

  41. Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R (2008) The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns. J Pediatr 152:801–806

    PubMed  Google Scholar 

  42. Hoyos AB (1999) Reduced incidence of necrotising enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 3:197–202

    PubMed  CAS  Google Scholar 

  43. Deshpande G, Rao S, Patole S (2007) Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet 369:1614–1620

    PubMed  Google Scholar 

  44. Deshpande G, Rao S, Patole S, Bulsara M (2010) Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 125:921–930

    PubMed  Google Scholar 

  45. Patole S (2011) Safety and efficacy of probiotics in the neonatal period. Nestle symposium presentation at the 52nd annual meeting of the European society for pediatric research (ESPR), New Castle, UK

    Google Scholar 

  46. Guthmann F, Kluthe C, Bührer C (2010) Probiotics for prevention of necrotising enterocolitis: an updated meta-analysis. Klin Pediatr 222:284–290

    CAS  Google Scholar 

  47. Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T (2011) Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (3):CD005496

    Google Scholar 

  48. Wang Q, Dong J, Zhu Y (2012) Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very low-birth-weight infants: an updated meta-analysis. J Pediatr Surg 47:241–248

    PubMed  Google Scholar 

  49. Soll RF (2010) Probiotics: are we ready for routine use? Pediatrics 125:1071–1072

    PubMed  Google Scholar 

  50. Garland SM, Jacobs SE, Tobin JM (2010) On behalf of the ProPrems study group. A cautionary note on instituting probiotics into routine clinical care for premature infants. Pediatrics 126:e741–2

    PubMed  Google Scholar 

  51. Miller M, Wilks M, Fleming P, Costeloe K (2012) Should the use of probiotics in the preterm be routine? Arch Dis Child Fetal Neonatal Ed 97:F70–F74

    Google Scholar 

  52. Tarnow-Mordi WO, Wilkinson D, Trivedi A, Brok J (2010) Probiotics reduce all-cause mortality and necrotizing enterocolitis: it is time to change practice. Pediatrics 125:1068–1070

    PubMed  Google Scholar 

  53. Barrington KJ (2011) Review: probiotics prevented necrotising enterocolitis and reduced mortality in preterm neonates. Arch Dis Child Education Ed 96:199. doi: 10.1136/adc.2011.214569

    Google Scholar 

  54. Kliegman RM, Willoughby RE (2005) Prevention of necrotizing enterocolitis with probiotics. Pediatrics 115:171–172

    PubMed  Google Scholar 

  55. Chou IC, Kuo HT, Chang JS, Wu SF, Chiu HY, Su BH, Lin HC (2010) Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. J Pediatr 156:393–396

    PubMed  Google Scholar 

  56. Sari FN, Eras Z, Dizdar EA, Erdeve O, Oguz SS, Uras N, Dilmen U (2012) Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Am J Perinatol 29(8):579–586. doi: 10.1055/s-0032–1311981

    PubMed  Google Scholar 

  57. Prescott SL, Wiltschut J, Taylor A, Westcott L, Jung W, Currie H, Dunstan JA (2008) Early markers of allergic disease in a primary prevention study using probiotics: 2.5-year follow-up phase. Allergy 63:1481–1490

    PubMed  CAS  Google Scholar 

  58. Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N (2010) Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci 13:253–262

    PubMed  CAS  Google Scholar 

  59. Bode L (2012) Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 22(9):1147–1162. doi: 10.1093/glycob/cws074

    PubMed  CAS  Google Scholar 

  60. Bode L, Rudloff S, Kunz C, Strobel S, Klein N (2004) Human milk oligosaccharides reduce platelet-neutrophil complex formation leading to a decrease in neutrophil beta 2 integrin expression. J Leukoc Biol 76:820–826

    PubMed  CAS  Google Scholar 

  61. Bode L, Jantscher-Krenn E (2012) Structure-function relationships of human milk oligosaccharides. Adv Nutr 3(3):383S–391S. doi: 10.3945/an.111.001404

    PubMed  CAS  Google Scholar 

  62. Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N, Choudhury B, Grishin AV, Ford HR, Bode L (2011) The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut (Epub ahead of print)

    Google Scholar 

  63. Butel MJ, Waligora-Dupriet AJ, Szylit O (2002) Oligofructose and experimental model of neonatal necrotising enterocolitis. Br J Nutr 87:S213–S219

    PubMed  CAS  Google Scholar 

  64. Srinivasjois R, Rao S, Patole S (2009) Prebiotic supplementation of formula in preterm neonates: a systematic review and meta-analysis of randomised controlled trials. Clin Nutr 28:237–242

    PubMed  CAS  Google Scholar 

  65. Westerbeek EA, Hensgens RL, Mihatsch WA, Boehm G, Lafeber HN, van Elburg RM (2011) The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants. Acta Paediatr 100:1426–1431

    PubMed  CAS  Google Scholar 

  66. Westerbeek EA, van den Berg JP, Lafeber HN, Fetter WP, Boehm G, Twisk JW, van Elburg RM (2010) Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 91:679–686

    PubMed  CAS  Google Scholar 

  67. Mihatsch WA, Hoegel J, Pohlandt F (2006) Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Acta Paediatr 95:843–848

    PubMed  Google Scholar 

  68. Modi N, Uthaya S, Fell J, Kulinskaya E (2010) A randomized, double-blind, controlled trial of the effect of prebiotic oligosaccharides on enteral tolerance in preterm infants (ISRCTN77444690). Pediatr Res 68:440–445

    PubMed  CAS  Google Scholar 

  69. Riskin A, Hochwald O, Bader D, Srugo I, Naftali G, Kugelman A, Cohen E, Mor F, Kaufman B, Shaoul R (2010) The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. J Pediatr 156:209–214

    PubMed  CAS  Google Scholar 

  70. Manzoni P, Rinaldi M, Cattani S et al (2009) Italian task force for the study and prevention of neonatal fungal infections, Italian society of neonatology. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 302:1421–1428

    PubMed  CAS  Google Scholar 

  71. Manzoni P, Stolfi I, Messner H et al (2012) Italian task force for the study and prevention of neonatal fungal infections—the Italian society of neonatology. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics 129:116–123

    PubMed  Google Scholar 

  72. Candy DCA, Devane SP (1997) Role of micro-organisms in necrotising enterocolitis. Semin Neonatol 2:255–262

    Google Scholar 

  73. Uauy RD, Fanaroff AA, Korones SB, Phillips EA, Phillips JB, Wright LL (1991) Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 119:630–638

    PubMed  CAS  Google Scholar 

  74. Patole S, Muller R (2004) Enteral feeding of preterm neonates—a survey of Australian neonatologists. J Matern Fetal Neonatal Med 16:309–314

    PubMed  CAS  Google Scholar 

  75. Klingenberg C, Embleton ND, Jacobs SE, O’Connell LA, Kuschel CA (2012) Enteral feeding practices in very preterm infants: an international survey. Arch Dis Child Fetal Neonatal Ed 97:F56–F61

    PubMed  Google Scholar 

  76. Patole SK, de Klerk N (2005) Impact of standardised feeding protocols on incidence of necrotising enterocolitis—a systematic review and meta analysis. Arch Dis Child Fetal Neonatal Ed 90:F147–F151

    PubMed  CAS  Google Scholar 

  77. Patole S, McGlone L, Muller R (2003) Virtual elimination of necrotising enterocolitis for 5 years—reasons? Med Hypotheses 61:617–622

    PubMed  CAS  Google Scholar 

  78. Kamitsuka MD, Horton MK, Williams MA (2000) The incidence of necrotizing enterocolitis after introducing standardized feeding schedules for infants between 1,250 and 2,500 g and less than 35 weeks of gestation. Pediatrics 105:379–384

    PubMed  CAS  Google Scholar 

  79. Brown EG, Sweet AY (1978) Preventing necrotizing enterocolitis in neonates. JAMA 24:2452–2454

    Google Scholar 

  80. Spritzer R, Koolen AM, Baerts W, Fetter WP, Lafeber HN, Sauer PJ (1988) A prolonged decline in the incidence of necrotizing enterocolitis after the introduction of a cautious feeding regimen. Acta Paediatr Scand 77:909–911

    PubMed  CAS  Google Scholar 

  81. Patole SK, Kadalraja R, Tuladhar R, Almonte R, Muller R, Whitehall JS (2000) Benefits of a standardised feeding regimen during a clinical trial in preterm neonates. Int J Clin Pract 54:429–431

    PubMed  CAS  Google Scholar 

  82. Premji SS, Chessell L, Paes B, Pinelli J, Jacobson K (2002) A matched cohort study of feeding practice guidelines for infants weighing less than 1,500 g. Adv Neonatal Care 2:27–36

    PubMed  Google Scholar 

  83. Kuzma-O’Reilly B, Duenas ML, Greecher C, Kimberlin L, Mujsce D, Miler D, Walker DJ (2003) Evaluation, development and implementation of potentially better practices in neonatal intensive care nutrition. Pediatrics 111:e461–e470

    PubMed  Google Scholar 

  84. McCallie KR, Lee HC, Mayer O, Cohen RS, Hintz SR, Rhine WD (2011) Improved outcomes with a standardized feeding protocol for very low birth weight infants. J Perinatol 31:S61–S67

    PubMed  CAS  Google Scholar 

  85. Street JL, Montgomery D, Alder SC, Lambert DK, Gerstmann DR, Christensen RD (2006) Implementing feeding guidelines for NICU patients < 2,000 g results in less variability in nutrition outcomes. JPEN J Parenter Enteral Nutr 30:515–518

    PubMed  Google Scholar 

  86. Christensen RD, Gordon PV, Besner GE (2010) Can we cut the incidence of necrotizing enterocolitis in half-today? Fetal Pediatr Pathol 29:185–198

    PubMed  CAS  Google Scholar 

  87. Celano P, Jumawan J, Horowitz C, Lau H, Koldovsky O (1977) Prenatal induction of sucrase activity in rat jejunum. Biochem J 162:469–472

    PubMed  CAS  Google Scholar 

  88. Moog F (1962) Developmental adaptations of alkaline phosphatises in the small intestine. Fed Proc 21:51–56

    PubMed  CAS  Google Scholar 

  89. Neu J, Ozaki CK, Angelides KJ (1986) Glucocorticoid-mediated alteration of fluidity of brush border membrane in rat small intestine. Pediatr Res 20:79–82

    PubMed  CAS  Google Scholar 

  90. Israel EJ, Schiffrin EJ, Carter EA, Freiberg E, Walker WA (1990) Prevention of necrotizing enterocolitis in the rat with prenatal cortisone. Gastroenterol 99:1333–1338

    CAS  Google Scholar 

  91. Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, Smith EO (1998) Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants. Pediatr Res 44:519–523

    PubMed  CAS  Google Scholar 

  92. Bousvaros A, Walker WA (1990) Development and function of the intestinal mucosal barrier. In: McDonald TT (ed) Ontogeny of the human system of the gut. CRC Press, Boca Raton, pp 2–22

    Google Scholar 

  93. Spencer T, McDonald TT (1990) The ontogeny of the immune system of the gut. CRC Press, Boca Raton, pp 23–50

    Google Scholar 

  94. Buchmiller TL, Shaw KS, Lam ML, Stokes R, Diamond JS, Fonkalsrud EW (1994) Effect of prenatal dexamethasone administration: fetal rabbit intestinal nutrient uptake and disaccharidase development. J Surg Res 57:274–279

    PubMed  CAS  Google Scholar 

  95. Nanthakumar NN, Young C, Ko JS, Meng D, Chen J, Buie T, Walker WA (2005) Glucocorticoid responsiveness in developing human intestine: possible role in prevention of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 288:G85–G92

    PubMed  CAS  Google Scholar 

  96. Bauer CR, Morrison JC, Poole WK, Korones SB, Boehm JJ, Rigatto H, Zachman RD (1984) A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy. Pediatrics 73:682–688

    PubMed  CAS  Google Scholar 

  97. Crowley P, Chalmers I, Keirse MJ (1990) The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 97:11–25

    PubMed  CAS  Google Scholar 

  98. Halac E, Halac J, Begue EF, Casanas JM et al (1990) Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. J Pediatr 117:132–138

    PubMed  CAS  Google Scholar 

  99. Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev (3):CD004454

    Google Scholar 

  100. ACOG Committee on Obstetric P (2011) ACOG committee opinion no 475: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 117:422–424

    Google Scholar 

  101. Carlo WA, McDonald SA, Fanaroff AA et al (2011) Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22–25 weeks’ gestation. JAMA 306:2348–2358

    PubMed  CAS  Google Scholar 

  102. Lucas A, Cole TJ (1990) Breast milk and neonatal necrotising enterocolitis. Lancet 336:1519–1523

    PubMed  CAS  Google Scholar 

  103. Caplan MS, Amer M, Jilling T (2002) The role of human milk in necrotising enterocolitis. Adv Exp Med Biol 503:83–90

    PubMed  Google Scholar 

  104. Hanson LA (1999) Human milk and host defence: immediate and long-term effects. Acta Paediatr 88:42–46

    CAS  Google Scholar 

  105. Schanler RJ (2001) The use of human milk for premature infants. Pediatr Clin North Am 48:207–219

    PubMed  CAS  Google Scholar 

  106. Goldman AS (2000) Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J Nutr 130:426S–431S

    PubMed  CAS  Google Scholar 

  107. Caplan M, Hsueh W, Kelly A, Donovan M (1990) Serum PAF acetylhydrolase increases during neonatal maturation. Prostaglandins 39:705–714

    PubMed  CAS  Google Scholar 

  108. Rabinowitz SS, Dzakpasu P, Piecuch S, Leblanc P, Valencia G, Kornecki E (2001) Platelet-activating factor in infants at risk for necrotizing enterocolitis. J Pediatr 138:81–86

    PubMed  CAS  Google Scholar 

  109. Caplan MS, Sun XM, Hseuh W, Hageman JR (1990) Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr 116:960–964

    PubMed  CAS  Google Scholar 

  110. Amer MD, Hedlund E, Rochester J, Caplan MS (2004) Platelet activating factor concentration in the stool of human newborns: effects of enteral feeding and neonatal necrotizing enterocolitis. Biol Neonate 85:159–166

    PubMed  CAS  Google Scholar 

  111. Furukawa M, Narahara H, Yasuda K, Johnston JM (1993) Presence of platelet-activating factor-acetylhydrolase in milk. J Lipid Res 34:1603–1609

    PubMed  CAS  Google Scholar 

  112. Akisu M, Kultursay N, Ozkayin N, Coker I, Huseyinov A (1998) Platelet-activating factor levels in term and preterm human milk. Biol Neonate 74:289–293

    PubMed  CAS  Google Scholar 

  113. Dvorak B, Halpern MD, Holubec H et al (2003) Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model. Pediatr Res 53:426–433

    PubMed  CAS  Google Scholar 

  114. McGuire W, Anthony MY (2003) Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review. Arch Dis Child Fetal Neonatal Ed 88:F11–F14

    PubMed  CAS  Google Scholar 

  115. Sullivan S, Schanler RJ, Kim JH, Patel AL et al (2010) An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156:562–567

    PubMed  CAS  Google Scholar 

  116. Ganapathy V, Hay JW, Kim JH (2012) Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Breastfeed Med 7:29–37

    PubMed  Google Scholar 

  117. Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF (2009) Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J Perinatol 29:57–62

    PubMed  CAS  Google Scholar 

  118. Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O’Shea TM (2007) Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinatol 27:428–433

    PubMed  CAS  Google Scholar 

  119. Castellote C, Casillas R, Ramírez-Santana C, Pérez-Cano FJ, Castell M, Moretones MG, López-Sabater MC, Franch A (2011) Premature delivery influences the immunological composition of colostrum and transitional and mature human milk. J Nutr 141:1181–1187

    PubMed  CAS  Google Scholar 

  120. Zamora SA, Amin HJ, McMillan DD et al (1998) Plasma L-arginine concentration oxygenation index, and systemic blood pressure in premature infants. Crit Care Med 26:1271–6

    Google Scholar 

  121. Becker RM, Wu G, Galanko JA et al (2000) Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 137:785–793

    PubMed  CAS  Google Scholar 

  122. Amin HJ, Zamora SA, McMillan DD, Fick GH (2002) Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr 140:425–441

    PubMed  CAS  Google Scholar 

  123. Amin HJ, Soraisham AS, Sauve RS (2009) Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis. J Paediatr Child Health 45:219–223

    PubMed  Google Scholar 

  124. Bell EF, Acarregui MJ (2008) Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev (1):CD000503

    Google Scholar 

  125. Morag I, Goldman M, Kuint J, Heyman E (2007) Excessive weight gain as a possible predictor of necrotizing enterocolitis in premature infants. Isr Med Assoc J 9:24–27

    PubMed  Google Scholar 

  126. Botsford KB, Weinstein RA, Boyer KM, Nathan C, Carman M, Paton JB (1986) Gram-negative bacilli in human milk feedings: quantitation and clinical consequences for premature infants. J Pediatr 109:707–710

    PubMed  CAS  Google Scholar 

  127. Schreiner RL, Eitzen H, Gfell MA et al (1979) Environmental contamination of continuous drip feedings. Pediatrics 63:232–237

    PubMed  CAS  Google Scholar 

  128. Carrion V, Egan EA (1990) Prevention of neonatal necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 11:317–323

    PubMed  CAS  Google Scholar 

  129. Guillet R, Stoll BJ, Cotton CM et al (2006) Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 117:e137–e142

    PubMed  Google Scholar 

  130. Terrin G, Passariello A, De Curtis M et al (2012) Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 129:e40–e45

    PubMed  Google Scholar 

  131. Faix RG, Polley TZ, Grasela TH (1988) A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. J Pediatr 112:271–277

    PubMed  CAS  Google Scholar 

  132. Brotschi B, Baenziger O et al (2009) Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J Perinat Med 37:701–705

    PubMed  Google Scholar 

  133. Bohnhorst B, Müller S, Dördelmann M, Peter CS, Petersen C, Poets CF (2003) Early feeding after necrotizing enterocolitis in preterm infants. J Pediatr 143:484–487

    PubMed  Google Scholar 

  134. Chan KL, Ng SP, Chan KW, Wo YH, Tam PK (2003) Pathogenesis of neonatal necrotizing enterocolitis: a study of the role of intraluminal pressure, age and bacterial concentration. Pediatr Surg Int 19:573–577

    PubMed  CAS  Google Scholar 

  135. Garstin WL, Kenny BD, McAneaney D, Patterson CC, Boston VV (1987) The role of intraluminal tension and pH in the development of necrotizing enterocolitis: an animal model. J Pediatr Surg 22:205–207

    PubMed  CAS  Google Scholar 

  136. Dolgin SE et al (1998) Alterations in respiratory status: early signs of severe necrotizing enterocolitis. J Pediatr Surg 33:856–858

    PubMed  CAS  Google Scholar 

  137. Dzakovic A, Notrica DM, Smith EO, Wesson DE, Jaksic T (2001) Primary peritoneal drainage for increasing ventilatory requirements in critically ill neonates with necrotizing enterocolitis. J Pediatric Surg 36:730–732

    CAS  Google Scholar 

  138. Pourcyrous M, Korones SB, Yang W, Boulden TF, Bada HS (2005) C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis. Pediatrics 116:1064–1069

    PubMed  Google Scholar 

  139. Hallstrom M, Koivisto AM, Janas M, Tammela O (2006) Laboratory parameters predictive of developing necrotizing enterocolitis in infants born before 33 weeks of gestation. J Pediatr Surg 41:792–798

    PubMed  Google Scholar 

  140. Kenton AB, O’Donovan D, Cass DL, Helmrath MA, Smith EO, Fernandes CJ et al (2005) Severe thrombocytopenia predicts outcome in neonates with necrotizing enterocolitis. J Perinatol 25:14–20

    PubMed  Google Scholar 

  141. Ververidis M, Kiely EM, Spitz L, Drake DP, Eaton S, Peirro A (2001) The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis. J Pediatr Surg 36:799–803

    PubMed  CAS  Google Scholar 

  142. Harris MC, D’Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L (2005) Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing enterocolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr 147:462–468

    PubMed  CAS  Google Scholar 

  143. Srinivasjois R, Nathan E, Doherty D, Patole S (2010) Prediction of progression of definite necrotising enterocolitis to need for surgery or death in preterm neonates. J Matern Fetal Neonat Med 23:695–700

    CAS  Google Scholar 

  144. Moss RL, Kalish LA, Duggan C et al (2008) Clinical parameters do not adequately predict outcome in necrotizing enterocolitis: a multi-institutional study. J Perinatol 28:665–674

    PubMed  CAS  Google Scholar 

  145. Kenton AB, Hegemier S, Smith EO, O’Donovan DJ, Brandt ML, Cass DL et al (2005) Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity. J Perinatol 25:173–177

    PubMed  Google Scholar 

  146. Mohamed A, Shah PS (2012) Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics 129:529–540

    PubMed  Google Scholar 

  147. Tepas JJ 3rd, Leaphart CL, Plumley D, Sharma R, Celso BG, Pieper P, Quilty J, Esquivia-Lee V (2010) Trajectory of metabolic derangement in infants with necrotizing enterocolitis should drive timing and technique of surgical intervention. J Am Coll Surgeons 210:847–852, 852–854

    Google Scholar 

  148. Bohnhorst B, Kuebler JF, Rau G, Gluer S, Ure B, Doerdelmann M (2011) Portal venous gas detected by ultrasound differentiates surgical NEC from other acquired neonatal intestinal diseases. Eur J Pediatr Surg 21:12–17

    PubMed  CAS  Google Scholar 

  149. Dilli D, Suna Oguz S, Erol R, Ozkan-Ulu H, Dumanli H, Dilmen U (2011) Does abdominal sonography provide additional information over abdominal plain radiography for diagnosis of necrotizing enterocolitis in neonates? Pediatr Surg Int 27:321–327

    PubMed  Google Scholar 

  150. McBride WJ, Roy S, Brudnicki A, Stringel G (2010) Correlation of complex ascites with intestinal gangrene and perforation in neonates with necrotizing enterocolitis. J Pediatr Surg 45:887–889

    PubMed  Google Scholar 

  151. Kim HY, Kim IO, Kim WS, Kang GH (2011) Bowel sonography in sepsis with pathological correlation: an experimental study. Pediatr Radiol 41:237–243

    PubMed  CAS  Google Scholar 

  152. Rao SC, Basani L, Simmer K, Samnakay N, Deshpande G (2011) Peritoneal drainage versus laparotomy as initial surgical treatment for perforated necrotizing enterocolitis or spontaneous intestinal perforation in preterm low birth weight infants. Cochrane Database Syst Rev (6):CD006182

    Google Scholar 

  153. Pike K, Brocklehurst P, Jones D, Kenyon S, Salt A, Taylor D, Marlow N (2012) Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: the ORACLE children study. Arch Dis Child Fetal Neonatal Ed (Epub ahead of print)

    Google Scholar 

  154. Patole S (2005) Prevention of necrotising enterocolitis—year 2004 and beyond. J Matern Fetal Neonat Med 17:69–80

    Google Scholar 

  155. Young C, Sharma R, Handfield M, Mai V, Neu J (2009) Biomarkers for infants at risk for necrotizing enterocolitis: clues to prevention? Pediatr Res 65:91R–97R

    PubMed  CAS  Google Scholar 

  156. Evennett N, Alexander N, Petrov M, Pierro A, Eaton S (2009) A systematic review of serologic tests in the diagnosis of necrotizing enterocolitis. J Pediatr Surg 44:2192–2201

    PubMed  Google Scholar 

  157. Thuijls G, Derikx JP, van Wijck K et al (2010) Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg 251:1174–1180

    PubMed  Google Scholar 

  158. Evennett NJ, Hall NJ, Pierro A, Eaton S (2010) Urinary intestinal fatty acid-binding protein concentration predicts extent of disease in necrotizing enterocolitis. J Pediatr Surg 45:735–740

    PubMed  Google Scholar 

  159. Aydemir O, Aydemir C, Sarikabadayi YU et al (2012) Fecal calprotectin levels are increased in infants with necrotizing enterocolitis. J Matern Fetal Neonat Med (Epub ahead of print)

    Google Scholar 

  160. Ayşe Selimoğlu M, Temel I, Yildirim C, Ozyalin F, Aktaş M, Karabiber H (2011) The role of fecal calprotectin and lactoferrin in the diagnosis of necrotizing enterocolitis. Pediatr Crit Care Med (Epub ahead of print)

    Google Scholar 

  161. Lam HS, Wong SP, Cheung HM, Chu WC, Wong RP, Chui KM, Liu FY, Li K, Fok TF, Ng PC (2011) Early diagnosis of intra-abdominal inflammation and sepsis by neutrophil CD64 expression in newborns. Neonatol 99:118–124

    CAS  Google Scholar 

  162. Tayman C, Tonbul A, Kahveci H, Uysal S, Koseoğlu B, Tatli MM, Dilmen U (2011) C5a, a complement activation product, is a useful marker in predicting the severity of necrotizing enterocolitis. Tohoku J Exp Med 224:143–150

    PubMed  CAS  Google Scholar 

  163. Pierro A, Hall N, Ade-Ajayi A, Curry J, Kiely EM (2004) Laparoscopy assists surgical decision making in infants with necrotizing enterocolitis. J Pediatr Surg 39:902–906

    PubMed  CAS  Google Scholar 

  164. Travadi J, Patole S, Charles A, Dvorak B, Doherty D, Simmer K (2006) Pentoxifylline reduces the incidence and severity of necrotizing enterocolitis in a neonatal rat model. Pediatr Res 60:185–189

    PubMed  CAS  Google Scholar 

  165. Nowicki PT, Dunaway DJ, Nankervis CA et al (2005) Endothelin-1 in human intestine resected for necrotizing enterocolitis. J Pediatr 146:805–810

    PubMed  CAS  Google Scholar 

  166. Athalye-Jape G, More K, Patole S (2012) Progress in the field of necrotising enterocolitis—year 2012. J Matern Fetal Neonat Med (Epub ahead of print)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sanjay Patole MD, DCH, FRACP, MSc, DrPH .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Patole, S. (2013). Prevention and Treatment of Necrotising Enterocolitis in Preterm Neonates. In: Patole, S. (eds) Nutrition for the Preterm Neonate. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6812-3_4

Download citation

Publish with us

Policies and ethics