DOI QR코드

DOI QR Code

An update on necrotizing enterocolitis: pathogenesis and preventive strategies

  • Lee, Jang-Hoon (Department of Pediatrics, Ajou University School of Medicine)
  • 투고 : 2011.07.29
  • 심사 : 2011.08.28
  • 발행 : 2011.09.15

초록

Necrotizing enterocolitis (NEC) is one of the most critical morbidities in preterm infants. The incidence of NEC is 7% in very-low-birthweight infants, and its mortality is 15 to 30%. Infants who survive NEC have various complications, such as nosocomial infection, malnutrition, growth failure, bronchopulmonary dysplasia, retinopathy of prematurity, and neurodevelopmental delays. The most important etiology in the pathogenesis of NEC is structural and immunological intestinal immaturity. In preterm infants with immature gastrointestinal tracts, development of NEC may be associated with a variety of factors, such as colonization with pathogenic bacteria, secondary ischemia, genetic polymorphisms conferring NEC susceptibility, anemia with red blood cell transfusion, and sensitization to cow milk proteins. To date, a variety of preventive strategies has been accepted or attempted in clinical practice with regard to the pathogenesis of NEC. These strategies include the use of breast feeding, various feeding strategies, probiotics, prebiotics, glutamine and arginine, and lactoferrin. There is substantial evidence for the efficacy of breast feeding and the use of probiotics in infants with birth weights above 1,000 g, and these strategies are commonly used in clinical practice. Other preventive strategies, however, require further research to establish their effect on NEC.

키워드

참고문헌

  1. Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CA, Schonberger LB. Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol 2006;20:498-506. https://doi.org/10.1111/j.1365-3016.2006.00756.x
  2. Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003;23:278-85. https://doi.org/10.1038/sj.jp.7210892
  3. Leviton A, Dammann O, Engelke S, Allred E, Kuban KC, O'Shea TM, et al. The clustering of disorders in infants born before the 28th week of gestation. Acta Paediatr 2010;99:1795-800. https://doi.org/10.1111/j.1651-2227.2010.01973.x
  4. 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. https://doi.org/10.1136/adc.2006.099929
  5. Allen A, Bell A, Mantle M, Pearson JP. The structure and physiology of gastrointestinal mucus. Adv Exp Med Biol 1982;144:115-33.
  6. Muresan Z, Paul DL, Goodenough DA. Occludin 1B, a variant of the tight junction protein occludin. Mol Biol Cell 2000;11:627-34.
  7. Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res 2008;63:117-23. https://doi.org/10.1203/PDR.0b013e31815ed64c
  8. Lotz M, Gutle D, Walther S, Menard S, Bogdan C, Hornef MW. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med 2006;203:973-84. https://doi.org/10.1084/jem.20050625
  9. Claud EC, Zhang X, Petrof EO, Sun J. Developmentally regulated tumor necrosis factor-alpha induced nuclear factor-kappaB activation in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol 2007; 292:G1411-9. https://doi.org/10.1152/ajpgi.00557.2006
  10. Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 2011;159:392-7. https://doi.org/10.1016/j.jpeds.2011.02.035
  11. Wang Y, Hoenig JD, Malin KJ, Qamar S, Petrof EO, Sun J, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J 2009;3:944-54. https://doi.org/10.1038/ismej.2009.37
  12. Claud EC, Walker WA. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 2001;15:1398-403. https://doi.org/10.1096/fj.00-0833hyp
  13. Caplan MS, Hedlund E, Adler L, Hsueh W. Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis. Pediatr Pathol 1994;14:1017-28. https://doi.org/10.3109/15513819409037698
  14. Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol 1994;21:205-18.
  15. Nowicki PT. Ischemia and necrotizing enterocolitis: where, when, and how. Semin Pediatr Surg 2005;14:152-8. https://doi.org/10.1053/j.sempedsurg.2005.05.003
  16. Nankervis CA, Giannone PJ, Reber KM. The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin Perinatol 2008;32:83-91. https://doi.org/10.1053/j.semperi.2008.01.003
  17. Moonen RM, Paulussen AD, Souren NY, Kessels AG, Rubio-Gozalbo ME, Villamor E. Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res 2007;62:188-90. https://doi.org/10.1203/PDR.0b013e3180a0324e
  18. Banyasz I, Bokodi G, Vasarhelyi B, Treszl A, Derzbach L, Szabo A, et al. Genetic polymorphisms for vascular endothelial growth factor in perinatal complications. Eur Cytokine Netw 2006;17:266-70.
  19. Treszl A, Kaposi A, Hajdu J, Szabo M, Tulassay T, Vasarhelyi B. The extent to which genotype information may add to the prediction of disturbed perinatal adaptation: none, minor, or major? Pediatr Res 2007;62:610-4. https://doi.org/10.1203/PDR.0b013e318155a0e1
  20. El-Dib M, Narang S, Lee E, Massaro AN, Aly H. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. J Perinatol 2011;31:183-7. https://doi.org/10.1038/jp.2010.157
  21. Singh R, Visintainer PF, Frantz ID 3rd, Shah BL, Meyer KM, Favila SA, et al. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J Perinatol 2011;31:176-82. https://doi.org/10.1038/jp.2010.145
  22. Reber KM, Nankervis CA, Nowicki PT. Newborn intestinal circulation. Physiology and pathophysiology. Clin Perinatol 2002;29:23-39. https://doi.org/10.1016/S0095-5108(03)00063-0
  23. Chuang SL, Hayes PJ, Ogundipe E, Haddad M, MacDonald TT, Fell JM. Cow's milk protein-specific T-helper type I/II cytokine responses in infants with necrotizing enterocolitis. Pediatr Allergy Immunol 2009;20:45-52. https://doi.org/10.1111/j.1399-3038.2008.00729.x
  24. Abdelhamid AE, Chuang SL, Hayes P, Fell JM. In vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotizing enterocolitis and sepsis. Pediatr Res 2011;69:165-9. https://doi.org/10.1203/PDR.0b013e31820263e7
  25. Boyd CA, Quigley MA, Brocklehurst P. Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2007;92:F169-75. https://doi.org/10.1136/adc.2005.089490
  26. McGuire W, Anthony MY. Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review. Arch Dis Child Fetal Neonatal Ed 2003;88:F11-4. https://doi.org/10.1136/fn.88.1.F11
  27. Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, et al. 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 2010;156:562-7.e1. https://doi.org/10.1016/j.jpeds.2009.10.040
  28. Quigley MA, Henderson G, Anthony MY, McGuire W. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev 2007;(4):CD002971.
  29. 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;111:529-34. https://doi.org/10.1542/peds.111.3.529
  30. Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2011;(3):CD001241.
  31. Bombell S, McGuire W. Early trophic feeding for very low birth weight infants. Cochrane Database Syst Rev 2009;(3):CD000504.
  32. Jeon GW, Park SE, Choi CW, Hwang JH, Chang YS, Park WS. The effects of early enteral feeding in extremely low birth-weight infants. Korean J Pediatr 2005;48:711-5.
  33. Premji S, Chessell L. Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. Cochrane Database Syst Rev 2003;(1):CD001819.
  34. Orrhage K, Nord CE. Factors controlling the bacterial colonization of the intestine in breastfed infants. Acta Paediatr Suppl 1999;88:47-57.
  35. Reid G, Howard J, Gan BS. Can bacterial interference prevent infection? Trends Microbiol 2001;9:424-8. https://doi.org/10.1016/S0966-842X(01)02132-1
  36. Duffy LC. Interactions mediating bacterial translocation in the immature intestine. J Nutr 2000;130(2S Suppl):432S-436S. https://doi.org/10.1093/jn/130.2.432S
  37. Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011;(3):CD005496.
  38. Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Hum Dev 2007;83:335-9. https://doi.org/10.1016/j.earlhumdev.2006.07.003
  39. Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen KF, Puntis JW, et al. Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2004;39:465-73. https://doi.org/10.1097/00005176-200411000-00003
  40. Riskin A, Hochwald O, Bader D, Srugo I, Naftali G, Kugelman A, et al. The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. J Pediatr 2010;156:209-14. https://doi.org/10.1016/j.jpeds.2009.09.006
  41. Westerbeek EA, van den Berg JP, Lafeber HN, Fetter WP, Boehm G, Twisk JW, et al. Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2010;91:679-86. https://doi.org/10.3945/ajcn.2009.28625
  42. Indrio F, Riezzo G, Raimondi F, Francavilla R, Montagna O, Valenzano ML, et al. Prebiotics improve gastric motility and gastric electrical activity in preterm newborns. J Pediatr Gastroenterol Nutr 2009;49:258-61. https://doi.org/10.1097/MPG.0b013e3181926aec
  43. Windmueller HG, Spaeth AE. Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate. J Biol Chem 1980;255:107-12.
  44. Li N, Lewis P, Samuelson D, Liboni K, Neu J. Glutamine regulates Caco-2 cell tight junction proteins. Am J Physiol Gastrointest Liver Physiol 2004;287:G726-33. https://doi.org/10.1152/ajpgi.00012.2004
  45. Tubman TR, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2008;(1):CD001457.
  46. Sevastiadou S, Malamitsi-Puchner A, Costalos C, Skouroliakou M, Briana DD, Antsaklis A, et al. The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/septicemia in premature neonates. J Matern Fetal Neonatal Med 2011;24:1294-300. https://doi.org/10.3109/14767058.2011.564240
  47. Castillo L, DeRojas-Walker T, Yu YM, Sanchez M, Chapman TE, Shannon D, et al. Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension. Pediatr Res 1995;38:17-24. https://doi.org/10.1203/00006450-199507000-00004
  48. Zamora SA, Amin HJ, McMillan DD, Kubes P, Fick GH, Butzner JD, et al. Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis. J Pediatr 1997;131:226-32. https://doi.org/10.1016/S0022-3476(97)70158-6
  49. Amin HJ, Zamora SA, McMillan DD, Fick GH, Butzner JD, Parsons HG, et al. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr 2002;140:425-31. https://doi.org/10.1067/mpd.2002.123289
  50. Buccigrossi V, de Marco G, Bruzzese E, Ombrato L, Bracale I, Polito G, et al. Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation. Pediatr Res 2007;61:410-4. https://doi.org/10.1203/pdr.0b013e3180332c8d
  51. Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009; 302:1421-8. https://doi.org/10.1001/jama.2009.1403
  52. Dvorak B, Halpern MD, Holubec H, Williams CS, McWilliam DL, Dominguez JA, et al. Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model. Am J Physiol Gastrointest Liver Physiol 2002;282:G156-64. https://doi.org/10.1152/ajpgi.00196.2001
  53. Feng J, El-Assal ON, Besner GE. Heparin-binding epidermal growth factor-like growth factor decreases the incidence of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 2006;41:144-9. https://doi.org/10.1016/j.jpedsurg.2005.10.018
  54. Nowicki PT, Dunaway DJ, Nankervis CA, Giannone PJ, Reber KM, Hammond SB, et al. Endothelin-1 in human intestine resected for necrotizing enterocolitis. J Pediatr 2005;146:805-10. https://doi.org/10.1016/j.jpeds.2005.01.046
  55. Ohtsuka Y, Okada K, Yamakawa Y, Ikuse T, Baba Y, Inage E, et al. $\omega$-3 fatty acids attenuate mucosal inflammation in premature rat pups. J Pediatr Surg 2011;46:489-95. https://doi.org/10.1016/j.jpedsurg.2010.07.032

피인용 문헌

  1. Oxidative stress and free radicals related diseases of the newborn vol.3, pp.7, 2012, https://doi.org/10.4236/abb.2012.327127
  2. Necrotizing Enterocolitis : Predictive Markers and Preventive Strategies vol.14, pp.3, 2011, https://doi.org/10.1542/neo.14-3-e113
  3. Necrotizing enterocolitis: The road to zero vol.19, pp.1, 2011, https://doi.org/10.1016/j.siny.2013.10.001
  4. ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool vol.12, pp.None, 2016, https://doi.org/10.2147/ndt.s116721
  5. Expression of MYPT1, CPI-17 and MLC20 in ileum of neonatal mouse NEC model and its significance vol.14, pp.3, 2011, https://doi.org/10.3892/etm.2017.4783
  6. The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside vol.2018, pp.None, 2011, https://doi.org/10.1155/2018/7483062
  7. Standardized feeding and probiotic supplementation for reducing necrotizing enterocolitis in preterm infants in a resource limited set up vol.72, pp.2, 2011, https://doi.org/10.1038/s41430-017-0040-7
  8. Extracellular Vesicles as a Potential Therapy for Neonatal Conditions: State of the Art and Challenges in Clinical Translation vol.11, pp.8, 2011, https://doi.org/10.3390/pharmaceutics11080404
  9. Lactobacillus reuteri DSM 17938 Improves Feeding Intolerance in Preterm Infants vol.22, pp.6, 2011, https://doi.org/10.5223/pghn.2019.22.6.545