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Necrotizing Enterocolitis in Newborns

Pathogenesis, Prevention and Management

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Abstract

Necrotizing enterocolitis (NEC) is primarily a disease process of the gastrointestinal (GI) tract of premature neonates that results in inflammation and bacterial invasion of the bowel wall. Despite advances in the care of premature infants, NEC remains one of the leading causes of morbidity and mortality in this population. It occurs in 1–5% of all neonatal intensive care admissions and 5–10% of all very low birthweight (<1500 g) infants. Although research has presented an interesting array of potential contributing factors, the precise aetiology of this multifactorial disease process remains elusive. Historically, it was believed that NEC arose predominantly from ischaemic injury to the immature GI tract, yet alternate plausible hypotheses indicate that many factors are likely to be involved. These may include issues related to the introduction and advancement of enteric feeding, alterations in the normal bacterial colonization of the GI tract, bacterial translocation and activation of the cytokine cascade, decreased epidermal growth factor, increased platelet activating factor, and mucosal damage from free radical production.

Clinical manifestations of NEC may be vague, including increased episodes of apnoea, desaturations, bradycardia, lethargy and temperature instability. There may also be GI-specific symptoms such as feeding intolerance, emesis, bloody stools, abdominal distention and tenderness, and abdominal wall discolouration. Laboratory values may be indicative of infection, coagulation abnormalities and fluid retention. Radiographic signs may include ileus, dilated or fixed intestinal loops, air in the intestinal wall or free air in the abdomen. Medical treatment typically consists of bowel rest and decompression, antibacterial therapy, and management of other haematological or electrolyte imbalances. Increased respiratory and cardiovascular support is sometimes needed. In neonates who do not respond adequately to medical management, or if pneumoperitoneum is present, surgical intervention may occur with either use of a peritoneal drain or laparotomy.

Advances in antenatal and neonatal care have resulted in increased survival of extremely preterm neonates. As this at-risk population continues to increase, an effective preventative strategy for NEC is needed. One preventative strategy is the use of antenatal corticosteroids to enhance maturation of the fetus if preterm delivery is likely. Recommendation of use of breast milk, early initiation of trophic feeds and judicoius advancement of enteric feeds are current postnatal strategies. Other preventative strategies that have been investigated include the use of oral antibacterials, antioxidants, supplementation of arginine and epidermal growth factor, none of which have changed clinical practice. Recent promising data indicate that prophylactic use of probiotics may play a role in preventing the onset of NEC. However, more large-scale, definitive studies are needed.

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References

  1. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet 2006; 368(9543): 1271–83

    Article  PubMed  Google Scholar 

  2. Gibbs K, Lin J, Holzman IR. Necrotising enterocolitis: the state of the science. Indian J Pediatr 2007; 74(1): 67–72

    Article  PubMed  Google Scholar 

  3. Kliegman RM. Models of the pathogenesis of necrotizing enterocolitis. J Pediatr 1990 Jul; 117 (1 Pt 2): S2–5

    Article  PubMed  CAS  Google Scholar 

  4. Panigrahi P. Necrotizing enterocolitis: a practical guide to its prevention and management. Pediatr Drugs 2006; 8(3): 151–65

    Article  Google Scholar 

  5. Hsueh W, Caplan MS, Qu X, et al. Neonatal necrotizing enterocolitis: clinical considerations and pathogenic concepts. Pediatr Dev Path 2002; 6(1): 6–23

    Article  Google Scholar 

  6. Henry M, Moss RL. Current issues in the management of necrotizing enterocolitis. Sem Perinatol 2004; 28(3): 221–33

    Article  Google Scholar 

  7. Anand RJ, Leaphart CL, Mollen KP, et al. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock 2007; 27(2): 124–33

    Article  PubMed  CAS  Google Scholar 

  8. Berseth CL. Gestational evolution of small intestine motility in preterm and term infants. J Pediatr 1989; 115(4): 646–51

    Article  PubMed  CAS  Google Scholar 

  9. Warner BW, Warner BB. Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr Surg 2005; 14(3): 175–80

    Article  PubMed  Google Scholar 

  10. Warner BB, Ryan AL, Seeger K, et al. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr 2007; 150(4): 358–63

    Article  PubMed  CAS  Google Scholar 

  11. Shin CE, Falcone RA, Stuart L, et al. Diminished epidermal growth factor levels in infants with necrotizing enterocolitis. J Pediatr Surg 2000; 35(2): 173–7

    Article  PubMed  CAS  Google Scholar 

  12. Rabinowitz SS, Dzakpasu P, Piecuch S, et al. Platelet-activating factor in infants at risk for necrotizing enterocolitis. J Pediatr 2001; 138(1): 81–6

    Article  PubMed  CAS  Google Scholar 

  13. Millar M, Wilks M, Costletoe K. Probiotics for preterm infants? Arch Dis Child Fetal Neonatal Ed 2003; 88(5): 354–8

    Article  Google Scholar 

  14. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr 2000; 30(1): 61–7

    Article  PubMed  CAS  Google Scholar 

  15. Berseth CL, Bisquera JA, Paje VU. Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2003; 111(3): 529–34

    Article  PubMed  Google Scholar 

  16. Sisk PM, Lovelady CA, Dillard RG, et al. Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinat 2007; 27(12): 428–33

    Article  CAS  Google Scholar 

  17. Lee JS, Polin RA. Treatment and prevention of necrotizing enterocolitis. Sem Neonatol 2003; 8(6): 449–59

    Article  Google Scholar 

  18. Updegrove K. Necrotizing enterocolitis: the evidence for use of human milk in prevention and treatment. J Hum Lact 2004; 20(3): 335–9

    Article  PubMed  Google Scholar 

  19. Henderson G, Craig S, Brocklehurst P, et al. Enterai feeding regimens and necrotizing enterocolitis in preterm infants: multi-center case-control study. Arch Dis Child Fetal Neonatal Ed. Epub 2007 Sep 3

  20. Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of disease. Curr Prob Pediatr 1987; 17(4): 213–88

    CAS  Google Scholar 

  21. Epelman M, Daneman A, Navarro OM, et al. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. Radiographics 2007; 27(2): 285–305

    Article  PubMed  Google Scholar 

  22. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging. Ann Surg 1978; 187(1): 1–7

    Article  PubMed  CAS  Google Scholar 

  23. 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(3): 193–8

    Article  Google Scholar 

  24. Goulet O, Sauvat F. Short bowel syndrome and intestinal transplantation in children. Curr Opin Clin Nutr Metab Care 2006; 9(3): 304–13

    Article  PubMed  Google Scholar 

  25. Blakely ML, Tyson JE, Lally KP, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. Pediatrics 2006; 117(4): 680–7

    Article  Google Scholar 

  26. Walsh MC, Kliegman RM, Hack M. Severity of necrotizing enterocolitis: influence on outcome at 2 years of age. Pediatrics 1989; 84(5): 808–14

    PubMed  CAS  Google Scholar 

  27. Merritt CR, Goldsmith JP, Sharp MJ. Sonographic detection of portal venous gas in infants with necrotizing enterocolitis. Am J Roentgenol 1984; 143(5): 1059–62

    CAS  Google Scholar 

  28. Faingold R, Daneman A, Tomlinson G, et al. Necrotizing enterocolitis: assessment of bowel viability with color doppler ultrasound. Radiology 2005; 235(2): 587–94

    Article  PubMed  Google Scholar 

  29. Silva CT, Daneman A, Navarro OM, et al. Correlation of sonographic findings and outcome in necrotizing enterocolitis. Pediatr Radiology 2007; 37(3): 274–82

    Article  Google Scholar 

  30. Moss RL, Dimmitt RA, Henry MC, et al. A meta-analysis of peritoneal drainage versus laparotomy for perforated necrotizing enterocolitis. J Pediatr Surg 2001 Aug; 36(8): 1210–3

    Article  PubMed  CAS  Google Scholar 

  31. Hall NJ, Curry J, Drake DP, et al. Resection and primary anastomosed is a valid surgical option for infants with necrotizing enterocolitis who weight less than 1000 g. Arch Surg 2005; 140(12): 1149–51

    Article  PubMed  CAS  Google Scholar 

  32. Griffiths DM, Forbes DA, Pemberton PJ, et al. Primary reanastomosis for necrotising enterocolitis: a 12-year experience. J Pediatr Surg 1989; 24(6): 515–8

    Article  PubMed  CAS  Google Scholar 

  33. Moss RL, Dimmitt RA, Blakely ML, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation. N Engl J Med 2006; 354(21): 2225–34

    Article  PubMed  CAS  Google Scholar 

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

  35. Kapiki A, Costalos C, Oikonomidou C, et al. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Hum Dev 2007; 83(5): 335–9

    Article  PubMed  CAS  Google Scholar 

  36. Lucas A, Cole TJ. Breast milk and neonatal necrotizing enterocolitis. Lancet 1990; 336(8730): 1519–23

    Article  PubMed  CAS  Google Scholar 

  37. Siu YK, Ng PC, Fung SCK, et al. Double blind, randomized, placebo controlled study of oral vancomycin in prevention of necrotizing enterocolitis in preterm, very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1998; 79(2): 105–9

    Article  Google Scholar 

  38. Grylack LJ, Scanion JW. Oral gentamicin therapy in the prevention of neonatal necrotizing enterocolitis: a controlled double-blind trial. Am J Dis Child 1978; 132(12): 1192–4

    PubMed  CAS  Google Scholar 

  39. Bury RG, Tudehope D. Enterai antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Database Syst Rev 2001; (1): CD000405

  40. Hammerman C, Bin-Nun A, Caplan M. Germ warfare: probiotics in defense of the premature gut. Clin Perinatol 2004; 31(3): 489–500

    Article  PubMed  Google Scholar 

  41. Costalos C, Skouteri V, Gounaris A, et al. Enterai feeding of premature infants with Saccharomyces boulardii. Early Hum Dev 2003; 74(2): 89–96

    Article  PubMed  CAS  Google Scholar 

  42. Dani C, Biadaioli R, Bertini G, et al. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants: a prospective study. Biol Neonate 2002; 82(2): 103–8

    Article  PubMed  CAS  Google Scholar 

  43. Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2005; 115(1): 1–4

    PubMed  Google Scholar 

  44. Bin-Nun A, Bromiker R, Wilschanski M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 2005; 147(2): 192–6

    Article  PubMed  Google Scholar 

  45. Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotizing enterocolitis in preterm infants with very low birthweight: a systematic review of randomized controlled trials. Lancet 2007; 369(9573): 1614–20

    Article  PubMed  Google Scholar 

  46. Kunz AN, Noel JM, Fairchok MP. Two cases of lactobacillus bacteremia during probiotic treatment of short gut syndrome. J Pediatr Gastroenterol Nutr 2004; 38(4): 457–8

    Article  PubMed  Google Scholar 

  47. Parracho H, McCartney AL, Gibson GR. Probiotics and prebiotics in infant nutrition. Proc Nutr Soc 2007; 66(3): 405–11

    Article  PubMed  Google Scholar 

  48. Lawrence G, Tudehope D, Baumann K, et al. Enterai human IgG for prevention of necrotizing enterocolitis: a placebo-controlled, randomized trial. Lancet 2001; 357(9274): 2090–4

    Article  PubMed  CAS  Google Scholar 

  49. Foster J, Cole M. Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates. Cochrane Database Syst Rev 2004; (1): CD001816

  50. Davis JM, Rosenfeld WN, Richter SE, et al. Safety and pharmacokinetics of multiple doses of recombinant human CuZn Superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome. Pediatrics 1997; 100(1): 24–30

    Article  PubMed  CAS  Google Scholar 

  51. Soghier LM, Brion LP. Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates. Cochrane Database Syst Rev 2006; (4): CD004869

  52. Dvorak B, Halpern MD, Holubec H, et al. Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model. Am J Physiol Gastrointest Liver Physiol 2002; 282(1): G156–64

    PubMed  CAS  Google Scholar 

  53. Sullivan PB, Lewindon PJ, Cheng C, et al. Intestinal mucosa remodeling by recombinant human epidermal growth factor 1–48 in neonates with severe necrotizing enterocolitis. J Pediatr Surg 2007; 42(3): 462–9

    Article  PubMed  Google Scholar 

  54. Becker RM, Wu G, Galanko JA, et al. Reduced serum amino acids concentrations in infants with necrotizing enterocolitis. J Pediatr 2000; 137(6): 785–93

    Article  PubMed  CAS  Google Scholar 

  55. Zamora SA, Amin HJ, McMillan DD, et al. Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis. J Pediatr 1997; 131(2): 226–32

    Article  PubMed  CAS  Google Scholar 

  56. Amin HJ, Zamora SA, McMillan DD, et al. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatric 2002; 140(4): 425–31

    Article  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest directly or indirectly related to the content of this review.

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Correspondence to Matthew J. Bizzarro.

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Thompson, A.M., Bizzarro, M.J. Necrotizing Enterocolitis in Newborns. Drugs 68, 1227–1238 (2008). https://doi.org/10.2165/00003495-200868090-00004

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