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Neonatology pp 1373-1393 | Cite as

Necrotizing Enterocolitis of Newborns

  • Sarah Bajorek
  • Josef Neu
Reference work entry

Abstract

The disease necrotizing enterocolitis (“NEC”) was first described over 150 years ago, however a major emphasis on understanding its pathogenesis and treatment has only burgeoned within the past 40 years (Obladen Neonatology 2009;96(4):203–210). NEC is a devastating process often progressing to death or severe morbidity within 24 hours of exhibiting initial symptoms. Currently, no clear definition of NEC exists. NEC has been a catchall term encompassing multiple pathophysiologic pathways leading to intestinal necrosis commonly seen in preterm infants. This heterogeneity and lack of a clear definition has contributed to confusion in our understanding of the pathogenesis of the most common forms of this disease. Understanding the most common form, “classical” NEC and the ability to separate that disease from other causes of intestinal damage that are termed “NEC” is important for diagnosis, prevention, and treatment. It is imperative to focus research efforts on the pathogenesis of classical NEC. We also need to find biomarkers that can be obtained noninvasively that are highly sensitive and specific and predict severity, in order to identify NEC early if we are to prevent its occurrence or be able to treat it before it progresses. This chapter will provide an overview of current concepts of NEC, including diagnosis, pathogenesis, prevention, and treatment options. Also highlighted are potential areas of future research.

References

  1. Abrahamsson T, Rautava S, Moore A, Neu J, Sherman P (2014) The time for a confirmative necrotizing enterocolitis probiotics prevention trial in the extremely low birth weight infant in North America is now! J Pediatr 2:(165).  https://doi.org/10.1016/j.jpeds.2014.05.012CrossRefGoogle Scholar
  2. Afrazi A, Branca MF, Sodhi CP et al (2014) Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J Biol Chem 289(14):9584–9599.  https://doi.org/10.1074/jbc.m113.526517CrossRefPubMedPubMedCentralGoogle Scholar
  3. Agwu JC (2005) In a preterm infant, does blood transfusion increase the risk of necrotizing enterocolitis? Arch Dis Child 90(1):102–103.  https://doi.org/10.1136/adc.2004.051532CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ahle M, Drott P, Andersson RE (2013) Epidemiology and trends of necrotizing enterocolitis in Sweden: 1987–2009. Pediatrics 132(2):e443–e451.  https://doi.org/10.1542/peds.2012-3847CrossRefPubMedGoogle Scholar
  5. Alexander VN, Northrup V, Bizzarro MJ (2011) Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 159(3):392–397.  https://doi.org/10.1016/j.jpeds.2011.02.035CrossRefPubMedPubMedCentralGoogle Scholar
  6. Amin HJ, Zamora SA, McMillan DD et al (2002) Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr 140(4):425–431.  https://doi.org/10.1067/mpd.2002.123289CrossRefPubMedGoogle Scholar
  7. Anand RJ, Leaphart CL, Mollen KP, Hackam DJ (2007) The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock 27(2):124–133.  https://doi.org/10.1097/01.shk.0000239774.02904.65CrossRefPubMedGoogle Scholar
  8. Ardissone A, De La Cruz D, Davis-Richardson A et al (2014) Meconium microbiome analysis identifies bacteria correlated with premature birth. Plos One 9(3):e90784CrossRefGoogle Scholar
  9. Arnon S, Litmanovitz I, Regev R et al (2005) Serum amyloid A protein is a useful inflammatory marker during late-onset sepsis in preterm infants. Biol Neonate 87(2):105–110.  https://doi.org/10.1159/000081979CrossRefPubMedGoogle Scholar
  10. Athalye-Jape G, Rao S, Patole S, More K (2013) Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very Low-birth-weight infants. Am J Perinatol 30(10):849–856.  https://doi.org/10.1055/s-0033-1333671CrossRefPubMedGoogle Scholar
  11. Autmizguine J, Hornik CP, Benjamin DK et al (2014) Anaerobic antimicrobial therapy after necrotizing enterocolitis in VLBW infants. Pediatrics 135(1):e117–e125.  https://doi.org/10.1542/peds.2014-2141CrossRefPubMedGoogle Scholar
  12. Aydemir C, Dilli D, Oguz SS et al (2011) Serum intestinal fatty acid binding protein level for early diagnosis and prediction of severity of necrotizing enterocolitis. Early Hum Dev 87(10):659–661.  https://doi.org/10.1016/j.earlhumdev.2011.05.004CrossRefPubMedGoogle Scholar
  13. Badolato R (1994) Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes. J Exp Med 180(1):203–209.  https://doi.org/10.1084/jem.180.1.203CrossRefPubMedGoogle Scholar
  14. Barlow B, Santulli T, Heird W, Pitt J, Blanc W, Schullinger J (1974) An experimental study of acute neonatal enterocolitis – the importance of breast milk. J Pediatr Surg. 5(9):587–595CrossRefGoogle Scholar
  15. Basani L, Simmer K, Samnakay N, Deshpande G (1996) 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.  https://doi.org/10.1002/14651858.cd006182.pub2, Rao SCCrossRefGoogle Scholar
  16. Bell MJ, Ternberg JL, Feigin RD et al (1978) Neonatal necrotizing enterocolitis. Ann Surg 187(1):1–7.  https://doi.org/10.1097/00000658-197801000-00001CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ben-Amor K, Heilig H, Smidt H, Vaughan EE, Abee T, de Vos WM (2005) Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol 71(8):4679–4689.  https://doi.org/10.1128/aem.71.8.4679-4689.2005CrossRefPubMedPubMedCentralGoogle Scholar
  18. Benkoe T, Reck C, Pones M et al (2014) Interleukin-8 predicts 60-day mortality in premature infants with necrotizing enterocolitis. J Pediatr Surg 49(3):385–389.  https://doi.org/10.1016/j.jpedsurg.2013.05.068CrossRefPubMedGoogle Scholar
  19. Bhandari V (2006) Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 117(6):1901–1906.  https://doi.org/10.1542/peds.2005-1414CrossRefPubMedGoogle Scholar
  20. Bin-Nun A, Booms C, Sabag N, Mevorach R, Algur N, Hammerman C (2014) Rapid fecal calprotectin (FC) analysis: point of care testing for diagnosing early necrotizing enterocolitis. Am J Perinatol 32(04):337–342.  https://doi.org/10.1055/s-0034-1384640CrossRefPubMedGoogle Scholar
  21. 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(3):423–428.  https://doi.org/10.1542/peds.109.3.423CrossRefPubMedGoogle Scholar
  22. Björkström MV, Hall L, Söderlund S, Håkansson EG, Håkansson S, Domellöf M (2009) Intestinal flora in very low-birth weight infants. Acta Paediatr 98(11):1762–1767.  https://doi.org/10.1111/j.1651-2227.2009.01471.xCrossRefPubMedGoogle Scholar
  23. Blakely M, Lally K, McDonald S, et al (2005) Postoperative outcomes of extremely low birth-weight infants with necrotizing enterocolitis or isolated intestinal perforation: a prospective cohort study by the NICHD Neonatal Research Network. Ann Surg 6(241). http://www.ncbi.nlm.nih.gov/pubmed/?term=blakely+ml+postoperative+outcomes+of+extremely+low+birth-weight+infants+with+necrotizing. Accessed 28 Sept 2015.
  24. Błaż W (2014) Usefulness of ultrasound examinations in the diagnostics of necrotizing enterocolitis. Pol J Radiol 79:1–9.  https://doi.org/10.12659/pjr.890539CrossRefGoogle Scholar
  25. Bor M, Verloove-Vanhorick SP, Brand R, Ruys JH (1988) Patent ductus arteriosus in a cohort of 1338 preterm infants: a collaborative study a. Paediatr Perinat Epidemiol 2(4):328–336.  https://doi.org/10.1111/j.1365-3016.1988.tb00227.xCrossRefPubMedGoogle Scholar
  26. Boyd CA, Quigley MA, Brocklehurst P (2007) Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 92(3):F169–F175.  https://doi.org/10.1136/adc.2005.089490CrossRefPubMedGoogle Scholar
  27. CDC. 128- moved: fatal gastrointestinal mucormycosis in an infant|fungal disease. http://www.cdc.gov/fungal/rhizopus-investigation.html. Accessed 19 Sept 2015.
  28. Chan KYY, Leung FWL, Lam HS et al (2012) Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants. PLoS One 7(5):e36977.  https://doi.org/10.1371/journal.pone.0036977, Neu J, edCrossRefPubMedPubMedCentralGoogle Scholar
  29. Chan KYY, Leung KT, Tam YH et al (2014) Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues. Ann Surg 260(6):1128–1137.  https://doi.org/10.1097/sla.0000000000000374CrossRefPubMedGoogle Scholar
  30. Cheu HW (1990) Breath hydrogen excretion in the premature neonate. Arch Pediatr Adolesc Med 144(2):197.  https://doi.org/10.1001/archpedi.1990.02150260077032CrossRefGoogle Scholar
  31. Claud EC, Walker WA (2001) Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 15:1398–1403CrossRefGoogle Scholar
  32. Claud EC, Keegan KP, Brulc JM et al (2013) Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome 1:20CrossRefGoogle Scholar
  33. Cole CR, Hansen NI, Higgins RD, Ziegler TR, Stoll BJ (2008) Very low birth weight preterm infants with surgical short bowel syndrome: incidence, morbidity and mortality, and growth outcomes at 18 to 22 months. Pediatrics 122(3):e573–e582.  https://doi.org/10.1542/peds.2007-3449CrossRefPubMedPubMedCentralGoogle Scholar
  34. Colgan SP, Taylor CT (2010) Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol 7(5):281–287.  https://doi.org/10.1038/nrgastro.2010.39CrossRefPubMedPubMedCentralGoogle Scholar
  35. Costeloe K (2016) Probiotics in preterm infants: the PiPS trial. In: Hot topics in neonatologyGoogle Scholar
  36. Cotten CM, Taylor S, Stoll B et al (2009) Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 123(1):58–66.  https://doi.org/10.1542/peds.2007-3423CrossRefPubMedPubMedCentralGoogle Scholar
  37. Coursey CA, Hollingsworth CL, Gaca AM, Maxfield C, DeLong D, Bisset G (2008) Radiologists’ agreement when using a 10-point scale to report abdominal radiographic findings of necrotizing enterocolitis in neonates and infants. Am J Roentgenol 191(1):190–197.  https://doi.org/10.2214/ajr.07.3558CrossRefGoogle Scholar
  38. Cucchiara S, Minella R, Iervolino C et al (1993) Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis. Arch Dis Child 69(6):655–659.  https://doi.org/10.1136/adc.69.6.655CrossRefPubMedPubMedCentralGoogle Scholar
  39. Däbritz J, Jenke A, Wirth S, Foell D (2012) Fecal phagocyte-specific S100A12 for diagnosing necrotizing enterocolitis. J Pediatr 161(6):1059–1064.  https://doi.org/10.1016/j.jpeds.2012.06.003CrossRefPubMedGoogle Scholar
  40. De Groote MA, Frank DN, Dowell E, Glode MP, Pace NR (2005) Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 24(3):278–280.  https://doi.org/10.1097/01.inf.0000154588.79356.e6CrossRefPubMedGoogle Scholar
  41. De Meij TGJ, van der Schee MPC, Berkhout DJC et al (2015) Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. J Pediatr 167(3):562–567.  https://doi.org/10.1016/j.jpeds.2015.05.044, e1CrossRefPubMedGoogle Scholar
  42. Derikx JP (2010) Non-invasive markers of gut wall integrity in health and disease. World J Gastroenterol 16(42):5272.  https://doi.org/10.3748/wjg.v16.i42.5272CrossRefPubMedPubMedCentralGoogle Scholar
  43. DeWitt AG, Charpie JR, Donohue JE, Yu S, Owens GE (2014) Splanchnic near-infrared spectroscopy and risk of necrotizing enterocolitis after neonatal heart surgery. Pediatr Cardiol 35(7):1286–1294.  https://doi.org/10.1007/s00246-014-0931-5CrossRefPubMedPubMedCentralGoogle Scholar
  44. DiGiulio DB, Romero R, Amogan HP et al (2008) Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One 3(8):e3056.  https://doi.org/10.1371/journal.pone.0003056, Fisk NMCrossRefPubMedPubMedCentralGoogle Scholar
  45. Donovan SM, Wang M, Li M, Friedberg I, Schwartz SL, Chapkin RS (2012) Host-microbe interactions in the neonatal intestine: role of human milk oligosaccharides. Adv Nutr (Bethesda, Md) 3:450S–455SCrossRefGoogle Scholar
  46. Edelson MB, Bagwell CE, Rozycki HJ (1999) Circulating Pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis. Pediatrics 103(4): 766–771.  https://doi.org/10.1542/peds.103.4.766CrossRefPubMedGoogle Scholar
  47. Elphick DA (2005) Paneth cells: their role in innate immunity and inflammatory disease. Gut 54(12):1802–1809.  https://doi.org/10.1136/gut.2005.068601CrossRefPubMedPubMedCentralGoogle Scholar
  48. Faingold R, Daneman A, Tomlinson G et al (2005) Necrotizing enterocolitis: assessment of bowel viability with color doppler US1. Radiology 235(2):587–594.  https://doi.org/10.1148/radiol.2352031718CrossRefPubMedGoogle Scholar
  49. Faix RG, Polley TZ, Grasela TH (1988) A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. J Pediatr 112(2):271–277.  https://doi.org/10.1016/s0022-3476(88)80069-6CrossRefPubMedGoogle Scholar
  50. Falkow S (2004) Opinion: Molecular Koch’s postulates applied to bacterial pathogenicity – a personal recollection 15 years later. Nat Rev Microbiol 2(1):67–72.  https://doi.org/10.1038/nrmicro799CrossRefPubMedGoogle Scholar
  51. Fitzgibbons SC, Ching Y, Yu D et al (2009) Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 44(6):1072–1076.  https://doi.org/10.1016/j.jpedsurg.2009.02.013CrossRefPubMedGoogle Scholar
  52. Fouhy F, Guinane CM, Hussey S et al (2012) High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 56(11): 5811–5820.  https://doi.org/10.1128/aac.00789-12CrossRefPubMedPubMedCentralGoogle Scholar
  53. Gatt M, Reddy BS, Macfie J (2006) Review article: bacterial translocation in the critically ill – evidence and methods of prevention. Aliment Pharmacol Ther 25(7): 741–757.  https://doi.org/10.1111/j.1365-2036.2006.03174.xCrossRefGoogle Scholar
  54. Goldmann DA, Leclair J, Macone A (1978) Bacterial colonization of neonates admitted to an intensive care environment. J Pediatr 93(2):288.  https://doi.org/10.1016/S0022-3476(78)80523-XCrossRefPubMedGoogle Scholar
  55. Gordon PV (2009) Understanding intestinal vulnerability to perforation in the extremely low birth weight infant. Pediatr Res 65(2):138–144.  https://doi.org/10.1203/pdr.0b013e31818c7920CrossRefPubMedGoogle Scholar
  56. Gordon P, Christensen R, Weitkamp J-H, Maheshwari A (2012) Mapping the new world of necrotizing enterocolitis (NEC): review and opinion. E-J Neonatol Res 4: 145–172Google Scholar
  57. Gordon PV, Clark R, Swanson JR, Spitzer A (2014) Can a national dataset generate a nomogram for necrotizing enterocolitis onset? J Perinatol 34(10):732–735.  https://doi.org/10.1038/jp.2014.137CrossRefPubMedGoogle Scholar
  58. Goulet O, Baglin-Gobet S, Talbotec C et al (2005) Outcome and long-term growth after extensive small bowel resection in the neonatal period: a survey of 87 children. Eur J Pediatr Surg 15(2):95–101.  https://doi.org/10.1055/s-2004-821214CrossRefPubMedGoogle Scholar
  59. Gupta RW, Tran L, Norori J et al (2013) Histamine-2 receptor blockers alter the fecal microbiota in premature infants. J Pediatr Gastroenterol Nutr 56: 397–400CrossRefGoogle Scholar
  60. Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH (2003) Necrotizing enterocolitis among neonates in the United States. J Perinatol 23(4):278–285.  https://doi.org/10.1038/sj.jp.7210892CrossRefPubMedGoogle Scholar
  61. Hammerman C, Goldschmidt D, Caplan MS et al (2002) Protective effect of bilirubin in ischemia-reperfusion injury in the rat intestine. J Pediatr Gastroenterol Nutr 35(3):344–349.  https://doi.org/10.1097/00005176-200209000-00020CrossRefPubMedGoogle Scholar
  62. Hanson LÅ, Korotkova M, Telemo E (2003) Breast-feeding, infant formulas, and the immune system. Ann Allergy Asthma Immunol 90(6):59–63.  https://doi.org/10.1016/s1081-1206(10)61662-6CrossRefPubMedGoogle Scholar
  63. Harris MC, D’Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L (2005) Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing entercolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr 147(4):462–468.  https://doi.org/10.1016/j.jpeds.2005.04.037CrossRefPubMedGoogle Scholar
  64. Hawiger J (2001) Innate immunity and inflammation: a transcriptional paradigm. Immunol Res 23(2-3):099–110.  https://doi.org/10.1385/IR:23:2-3:099CrossRefGoogle Scholar
  65. He R (2002) Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood 101(4):1572–1581.  https://doi.org/10.1182/blood-2002-05-1431CrossRefPubMedGoogle Scholar
  66. Hintz SR (2005) Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 115(3):696–703.  https://doi.org/10.1542/peds.2004-0569CrossRefPubMedGoogle Scholar
  67. Ho T, Dukhovny D, Zupancic JA, Goldmann DA, Horbar JD, Pursley DM (2015) Choosing wisely in newborn medicine: five opportunities to increase value. Pediatrics 136:e482–e489CrossRefGoogle Scholar
  68. Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CA, Schonberger LB (2006) Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol 20(6):498–506.  https://doi.org/10.1111/j.1365-3016.2006.00756.xCrossRefPubMedGoogle Scholar
  69. Horwitz JR, Lally KP, Cheu HW, David Vazquez W, Grosfeld JL, Ziegler MM (1995) Complications after surgical intervention for necrotizing enterocolitis: a multicenter review. J Pediatr Surg 30(7):994–999.  https://doi.org/10.1016/0022-3468(95)90328-3CrossRefPubMedGoogle Scholar
  70. Huda S, Chaudhery S, Ibrahim H, Pramanik A (2014) Neonatal necrotizing enterocolitis: clinical challenges, pathophysiology and management. Pathophysiology 21(1):3–12.  https://doi.org/10.1016/j.pathophys.2013.11.009CrossRefPubMedGoogle Scholar
  71. Hunter C, Dimaguila MAV, Gal P et al (2012) Effect of routine probiotic, lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis. BMC Pediatr 12(1):142.  https://doi.org/10.1186/1471-2431-12-142CrossRefPubMedPubMedCentralGoogle Scholar
  72. Hutter JJ, Hathaway WE, Wayne ER (1976) Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 88(6):1026–1031.  https://doi.org/10.1016/s0022-3476(76)81069-4CrossRefPubMedGoogle Scholar
  73. Hyman PE, Clarke DD, Everett SL et al (1985) Gastric acid secretory function in preterm infants. J Pediatr 106(3): 467–471.  https://doi.org/10.1016/s0022-3476(85)80682-xCrossRefPubMedGoogle Scholar
  74. Ian W, Garstin H, Boston VE (1987) Sequential assay of expired breath hydrogen as a means of predicting necrotizing enterocolitis in susceptible infants. J Pediatr Surg 22(3):208–210.  https://doi.org/10.1016/s0022-3468(87)80329-9CrossRefGoogle Scholar
  75. Jacobs S, Tobin J, Opie G (2013) Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics 132(6):X9–X9.  https://doi.org/10.1542/peds.2013-1339dCrossRefGoogle Scholar
  76. Jenke A, Ruf E-M, Hoppe T, Heldmann M, Wirth S (2011) Bifidobacterium septicaemia in an extremely low-birthweight infant under probiotic therapy. Arch Dis Childhood Fetal Neonatal Ed 97(3):F217–F218.  https://doi.org/10.1136/archdischild-2011-300838CrossRefGoogle Scholar
  77. Jilling T, Simon D, Lu J et al (2006) The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. J Immunol 177(5):3273–3282.  https://doi.org/10.4049/jimmunol.177.5.3273CrossRefPubMedPubMedCentralGoogle Scholar
  78. Jones BA, Hull MA, Kim HB (2010) Autologous intestinal reconstruction surgery for intestinal failure management. Curr Opin Organ Transplant 15(3):341–345.  https://doi.org/10.1097/mot.0b013e328338c2c0CrossRefPubMedGoogle Scholar
  79. Josephson CD, Wesolowski A, Bao G et al (2010) Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants? J Pediatr 157(6):972–978.  https://doi.org/10.1016/j.jpeds.2010.05.054, e3CrossRefPubMedPubMedCentralGoogle Scholar
  80. Kafetzis DA, Skevaki C, Costalos C (2003) Neonatal necrotizing enterocolitis: an overview. Curr Opin Infect Dis 16(4):349–355.  https://doi.org/10.1097/00001432-200308000-00007CrossRefPubMedGoogle Scholar
  81. Kazez A, Küçükaydin N, Küçükaydin M, Kontaş O, Okur H, Doǧan P (1997) A model of hypoxia-induced necrotizing enterocolitis: the role of distension. J Pediatr Surg 32(10):1466–1469.  https://doi.org/10.1016/s0022-3468(97)90564-9CrossRefPubMedGoogle Scholar
  82. Kilpinen S, Henttinen T, Lahdenpohja N, Hulkkonen J, Hurme M (1996) Signals leading to the activation of NF-kappaB transcription factor are stronger in neonatal than adult T lymphocytes. Scand J Immunol 44(1):85–88.  https://doi.org/10.1046/j.1365-3083.1996.d01-277.xCrossRefPubMedGoogle Scholar
  83. Konikoff MR, Denson LA (2006) Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis 12(6):524–534.  https://doi.org/10.1097/00054725-200606000-00013CrossRefPubMedGoogle Scholar
  84. Konnikova Y, Zaman MM, Makda M, D’Onofrio D, Freedman SD, Martin CR (2015) Late enteral feedings are associated with intestinal inflammation and adverse neonatal outcomes. PLoS One 10:e0132924CrossRefGoogle Scholar
  85. Konturek SK, Konturek PC (1995) Role of nitric oxide in the digestive system. Digestion 56(1):1–13.  https://doi.org/10.1159/000201214CrossRefPubMedGoogle Scholar
  86. (2012) Lactoferrin immunoprophylaxis for very preterm infants. Arch Dis Childhood Fetal Neonatal Ed. 98(1):F2–F4.  https://doi.org/10.1136/archdischild-2011-301273
  87. Ladd AP, Rescorla FJ, West KW, Scherer L, Engum SA, Grosfeld JL (1998) Long-term follow-up after bowel resection for necrotizing enterocolitis: factors affecting outcome. J Pediatr Surg 33(7):967–972.  https://doi.org/10.1016/s0022-3468(98)90516-4CrossRefPubMedGoogle Scholar
  88. Le Mandat Schultz A, Bonnard A, Berrebi D et al (2007) Expression of TLR-2, TLR-4, NOD2 and pNF-kB in a neonatal rat model of necrotizing enterocolitis. PLoS One 2(10):e1102.  https://doi.org/10.1371/journal.pone.0001102, Gold J, edCrossRefPubMedPubMedCentralGoogle Scholar
  89. Leaphart CL, Cavallo J, Gribar SC et al (2007) A critical role for TLR4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. J Immunol 179(7):4808–4820.  https://doi.org/10.4049/jimmunol.179.7.4808CrossRefPubMedGoogle Scholar
  90. Lieberman JM, Sacchettini J, Marks C, Marks WH (1997) Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 121(3):335–342.  https://doi.org/10.1016/s0039-6060(97)90363-9CrossRefPubMedGoogle Scholar
  91. Lin PW, Stoll BJ (2006) Necrotising enterocolitis. Lancet 368(9543):1271–1283.  https://doi.org/10.1016/s0140-6736(06)69525-1CrossRefPubMedGoogle Scholar
  92. Lin H, Hsu C, Chen H, et al (2008) Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics 4(122).  https://doi.org/10.1542/peds.2007-3007CrossRefGoogle Scholar
  93. Lucas A, Cole TJ (1990) Breast milk and neonatal necrotising enterocolitis. Lancet 336(8730-8731):1519–1523.  https://doi.org/10.1016/0140-6736(90)93304-8CrossRefPubMedGoogle Scholar
  94. Maayan-Metzger A, Itzchak A, Mazkereth R, Kuint J (2004) Necrotizing enterocolitis in full-term infants: case–control study and review of the literature. J Perinatol 24(8):494–499.  https://doi.org/10.1038/sj.jp.7211135CrossRefPubMedGoogle Scholar
  95. MacDonald TT (2003) The mucosal immune system. Parasite Immunol 25(5):235–246.  https://doi.org/10.1046/j.1365-3024.2003.00632.xCrossRefPubMedGoogle Scholar
  96. Maheshwari A, Schelonka RL, Dimmitt RA et al (2014) Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res 76(1):100–108.  https://doi.org/10.1038/pr.2014.48CrossRefPubMedPubMedCentralGoogle Scholar
  97. Mai V, Young CM, Ukhanova M et al (2011) Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One 6(6):e20647.  https://doi.org/10.1371/journal.pone.0020647, Chakravortty DCrossRefPubMedPubMedCentralGoogle Scholar
  98. Mally P, Golombek SG, Mishra R et al (2006) Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol 23(08):451.  https://doi.org/10.1055/s-2006-951300CrossRefPubMedGoogle Scholar
  99. Maury CPJ (1985) Comparative study of serum amyloid a protein and C-reactive protein in disease. Clin Sci 68(2):233–238.  https://doi.org/10.1042/cs0680233CrossRefPubMedGoogle Scholar
  100. McElroy SJ, Underwood MA, Sherman MP (2013) Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease pathogenesis. Neonatology 103:10–20CrossRefGoogle Scholar
  101. Meier PP, Bode L (2013) Health, nutrition, and cost outcomes of human milk feedings for very low birthweight infants. Adv Nutr: Int Rev J 4(6):670–671.  https://doi.org/10.3945/an.113.004457CrossRefGoogle Scholar
  102. Mihatsch WA, Braegger CP, Decsi T et al (2012) Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants. Clin Nutr 31(1):6–15.  https://doi.org/10.1016/j.clnu.2011.09.004CrossRefGoogle Scholar
  103. Minekawa R, Takeda T, Sakata M, Hayashi M (2004) Human breast milk suppresses the transcriptional regulation of IL-1 -induced NF- B signaling in human intestinal cells. AJP: Cell Physiol 287(5):C1404–C1411.  https://doi.org/10.1152/ajpcell.00471.2003CrossRefGoogle Scholar
  104. Mohan P, Abrams SA (2015) Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in premature infants. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD007137CrossRefGoogle Scholar
  105. Morgan J, Young L (2014) Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.cd001970.pub5, McGuire WCrossRefGoogle Scholar
  106. Moss LR, Dimmitt RA, Henry MCW, Geraghty N, Efron B (2001) A meta-analysis of peritoneal drainage versus laparotomy for perforated necrotizing enterocolitis. J Pediatr Surg 36(8):1210.  https://doi.org/10.1053/jpsu.2001.25764CrossRefPubMedGoogle Scholar
  107. Neu J, Walker WA (2011) Necrotizing enterocolitis. N Engl J Med 364(3):255–264.  https://doi.org/10.1056/nejmra1005408CrossRefPubMedPubMedCentralGoogle Scholar
  108. Ng PC, Cheng SH, Chui KM et al (1997) Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Childhood Fetal Neonatal Ed 77(3):F221–F227.  https://doi.org/10.1136/fn.77.3.f221CrossRefGoogle Scholar
  109. Ng PC, Ang IL, Chiu RWK et al (2010) Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. J Clin Investig 120(8):2989–3000.  https://doi.org/10.1172/jci40196CrossRefPubMedGoogle Scholar
  110. Ng EWY, Poon TCW, Lam HS et al (2013) Gut-associated biomarkers L-FABP, I-FABP, and TFF3 and LIT score for diagnosis of surgical necrotizing enterocolitis in preterm infants. Ann Surg 258(6):1111–1118.  https://doi.org/10.1097/sla.0b013e318288ea96CrossRefPubMedGoogle Scholar
  111. Oh S, Young C, Gravenstein N, Islam S, Neu J (2010) Monitoring technologies in the neonatal intensive care unit: implications for the detection of necrotizing enterocolitis. J Perinatol 30(11):701–708.  https://doi.org/10.1038/jp.2010.9CrossRefPubMedGoogle Scholar
  112. Orenstein SR, Shalaby TM, Devandry SN et al (2003) Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial. Aliment Pharmacol Ther 17(9):1097–1107.  https://doi.org/10.1046/j.1365-2036.2003.01559CrossRefPubMedGoogle Scholar
  113. Orenstein S, Gremse D, Pantaleon C, Kling D, Rotenberg K (2005) Nizatidine for the treatment of pediatric gastroesophageal reflux symptoms: an open-label, multiple-dose, randomized, multicenter clinical trial in 210 children. Clin Ther 27(4):472–483.  https://doi.org/10.1016/j.clinthera.2005.04.008CrossRefPubMedGoogle Scholar
  114. Ostlie DJ, Spilde TL, St Peter SD et al (2003) Necrotizing enterocolitis in full-term infants. J Pediatr Surg 38(7): 1039–1042.  https://doi.org/10.1016/s0022-3468(03)00187-8CrossRefPubMedGoogle Scholar
  115. Otte J-M, Cario E, Podolsky DK (2004) Mechanisms of cross hyporesponsiveness to toll-like receptor bacterial ligands in intestinal epithelial cells☆. Gastroenterology 126(4):1054–1070.  https://doi.org/10.1053/j.gastro.2004.01.007CrossRefPubMedGoogle Scholar
  116. Pelsers MMAL, Hermens WT, Glatz JFC (2005) Fatty acid-binding proteins as plasma markers of tissue injury. Clin Chim Acta 352(s 1–2):15–35.  https://doi.org/10.1016/j.cccn.2004.09.001CrossRefPubMedGoogle Scholar
  117. Potoka DA, Upperman JS, Nadler EP et al (2002) NF-kB inhibition enhances peroxynitrite-induced enterocyte apoptosis. J Surg Res 106(1):7–14.  https://doi.org/10.1006/jsre.2002.6423CrossRefPubMedGoogle Scholar
  118. Pourcyrous M (2005) C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis. Pediatrics 116(5):1064–1069.  https://doi.org/10.1542/peds.2004-1806CrossRefPubMedGoogle Scholar
  119. Quigley M, McGuire W (2014) Formula versus donor breast milk for feeding preterm or low birth weight infants.  https://doi.org/10.1002/14651858.CD002971.pub3
  120. Rehan VK, Seshia MMK, Johnston B, Reed M, Wilmot D, Cook V (1999) Observer variability in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis. Clin Pediatr 38(11):637–643.  https://doi.org/10.1177/000992289903801102CrossRefGoogle Scholar
  121. Remon J, Kampanatkosol R, Kaul RR, Muraskas JK, Christensen RD, Maheshwari A (2014) Acute drop in blood monocyte count differentiates NEC from other causes of feeding intolerance. J Perinatol 34(7):549–554.  https://doi.org/10.1038/jp.2014.52CrossRefPubMedPubMedCentralGoogle Scholar
  122. Rojas MA, Lozano JM, Rodriguez VA et al (2012) Prophylactic probiotics to prevent death and nosocomial infection in preterm infants. Pediatrics 130(5):e1113–e1120.  https://doi.org/10.1542/peds.2011-3584CrossRefPubMedGoogle Scholar
  123. Rouge C, Piloquet H, Butel M-J et al (2009) Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 89(6):1828–1835.  https://doi.org/10.3945/ajcn.2008.26919CrossRefPubMedGoogle Scholar
  124. Salminen MK, Rautelin H, Tynkkynen S et al (2004) Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 38(1):62.  https://doi.org/10.1086/380455CrossRefPubMedGoogle Scholar
  125. Salzman NH, Polin RA, Harris MC et al (1998) Enteric defensin expression in necrotizing enterocolitis. Pediatr Res 44(1):20–26.  https://doi.org/10.1203/00006450-199807000-00003CrossRefPubMedGoogle Scholar
  126. Salzman NH, Underwood MA, Bevins CL (2007) Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol 19(2):70–83.  https://doi.org/10.1016/j.smim.2007.04.002CrossRefGoogle Scholar
  127. Sampath V, Le M, Lane L et al (2011) The NFKB1 (g.-24519delATTG) variant is associated with necrotizing enterocolitis (NEC) in premature infants. J Surg Res 169(1):e51–e57.  https://doi.org/10.1016/j.jss.2011.03.017CrossRefPubMedGoogle Scholar
  128. Sangild PT, Petersen YM, Elnif J, Schmidt MH, Buddington RK, Burrin DG (2000) Premature and term newborn pigs differ in their intestinal responses to parenteral and enteral nutrition. Gastroenterology 118(4):A76.  https://doi.org/10.1016/s0016-5085(00)82381-1CrossRefGoogle Scholar
  129. Sangild PT, Thymann T, Schmidt M, Stoll B, Burrin DG, Buddington RK (2013) Invited review: the preterm pig as a model in pediatric gastroenterology. J Anim Sci 91:4713–4729CrossRefGoogle Scholar
  130. Santulli T, Schullinger J, Heird W, Gongaware R, Wigger J (1975) Acute necrotizing enterocolitis in infancy: a review of 64 cases. Pediatrics 55(3):376–387PubMedGoogle Scholar
  131. Sedda S, Marafini I, Figliuzzi MM, Pallone F, Monteleone G (2014) An overview of the role of innate lymphoid cells in gut infections and inflammation. Mediators Inflamm 2014:1–7.  https://doi.org/10.1155/2014/235460CrossRefGoogle Scholar
  132. Shah P (2004) Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD004339.pub2CrossRefPubMedGoogle Scholar
  133. Singh R, Visintainer PF, Frantz ID et al (2011) Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J Perinatol 31(3):176–182.  https://doi.org/10.1038/jp.2010.145CrossRefPubMedPubMedCentralGoogle Scholar
  134. Smith B, Bodé S, Petersen BL et al (2011) Community analysis of bacteria colonizing intestinal tissue of neonates with necrotizing enterocolitis. BMC Microbiol 11(1):73.  https://doi.org/10.1186/1471-2180-11-73CrossRefPubMedPubMedCentralGoogle Scholar
  135. Smith JM, Skeans MA, Horslen SP et al (2014) OPTN/SRTR 2012 annual data report: intestine. Am J Transplant 14(S1):97–111.  https://doi.org/10.1111/ajt.12582CrossRefPubMedGoogle Scholar
  136. Sola MC, Del Vecchio A, Rimsza LM (2000) Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Clin Perinatol 27(3):655–679.  https://doi.org/10.1016/s0095-5108(05)70044-0CrossRefPubMedGoogle Scholar
  137. Soliman A, Michelsen KS, Karahashi H et al (2010) Platelet-activating factor induces TLR4 expression in intestinal epithelial cells: implication for the pathogenesis of necrotizing enterocolitis. PLoS One 5(10):e15044.  https://doi.org/10.1371/journal.pone.0015044, Unutmaz D, edCrossRefPubMedPubMedCentralGoogle Scholar
  138. Sonntag J, Grimmer I, Scholz T, Metze B, Wit J, Obladen M (2000) Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis. Acta Paediatr (Oslo, Norway : 1992) 5(89):528–532CrossRefGoogle Scholar
  139. Spencer AU, Kovacevich D, McKinney-Barnett M et al (2008) Pediatric short-bowel syndrome: the cost of comprehensive care. Am J Clin Nutr 88(6):1552–1559.  https://doi.org/10.3945/ajcn.2008.26007CrossRefPubMedGoogle Scholar
  140. Stewart C (2015) Early gut microbiome and polymicrobial infection. Encycl Metagenomics pp. 143–150.  https://doi.org/10.1007/978-1-4899-7475-4_798Google Scholar
  141. Stoll B, Cismowski M, Hamrick S, Bhatia A (2013) Cytokine levels in the preterm infant with neonatal intestinal injury. Am J Perinatol 31(06):489–496.  https://doi.org/10.1055/s-0033-1353437CrossRefPubMedGoogle Scholar
  142. Stringer MD, Brereton RJ, Drake DP, Kiely EM, Capps SNJ, Spitz L (1993) Recurrent necrotizing enterocolitis. J Pediatr Surg 28(8):979–981.  https://doi.org/10.1016/0022-3468(93)90496-8CrossRefPubMedGoogle Scholar
  143. Sudan D, Thompson J, Botha J et al (2007) Comparison of intestinal lengthening procedures for patients with short bowel syndrome. Ann Surg 246(4):593–604.  https://doi.org/10.1097/sla.0b013e318155aa0cCrossRefPubMedGoogle Scholar
  144. Sullivan S, Schanler RJ, Kim JH 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(4):562–567.  https://doi.org/10.1016/j.jpeds.2009.10.040CrossRefPubMedGoogle Scholar
  145. Taft DH, Ambalavanan N, Schibler KR et al (2014) Intestinal microbiota of preterm infants differ over time and between hospitals. Microbiome 2(1):36.  https://doi.org/10.1186/2049-2618-2-36CrossRefPubMedPubMedCentralGoogle Scholar
  146. Tam AL, Camberos A, Applebaum H (2002) Surgical decision making in necrotizing enterocolitis and focal intestinal perforation: predictive value of radiologic findings. J Pediatr Surg 37(12):1688–1691.  https://doi.org/10.1053/jpsu.2002.36696CrossRefPubMedGoogle Scholar
  147. Tepas JJ, Sharma R, Hudak ML, Garrison RD, Pieper P (2006) Coming full circle: an evidence-based definition of the timing and type of surgical management of very low-birth-weight (<1000 g) infants with signs of acute intestinal perforation. J Pediatr Surg 41(2):418–422.  https://doi.org/10.1016/j.jpedsurg.2005.11.041CrossRefPubMedGoogle Scholar
  148. Thomas DW, Greer FR (2010) Probiotics and prebiotics in pediatrics. Pediatrics 126:1217–1231CrossRefGoogle Scholar
  149. Thuijls G, Derikx JPM, van Wijck K et al (2010) Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg 251(6):1174–1180.  https://doi.org/10.1097/sla.0b013e3181d778c4CrossRefPubMedGoogle Scholar
  150. Tomomasa T, Takahashi A, Nako Y et al (1999) Analysis of gastrointestinal sounds in infants with pyloric stenosis before and after pyloromyotomy. Pediatrics 104(5):e60–e60.  https://doi.org/10.1542/peds.104.5.e60CrossRefPubMedGoogle Scholar
  151. Torrazza M, Li N, Young C et al (2013) Pilot study using proteomics to identify predictive biomarkers of necrotizing enterocolitis from buccal swabs in very low birth weight infants. Neonatology 104(3):234.  https://doi.org/10.1159/000353721CrossRefGoogle Scholar
  152. Torrazza RM, Li N, Neu J (2014) Decoding the enigma of necrotizing enterocolitis in premature infants. Pathophysiology 21(1):21–27.  https://doi.org/10.1016/j.pathophys.2013.11.011CrossRefPubMedGoogle Scholar
  153. Turner D, Hammerman C, Rudensky B et al (2007) Low levels of procalcitonin during episodes of necrotizing enterocolitis. Dig Dis Sci 52(11):2972–2976.  https://doi.org/10.1007/s10620-007-9763-yCrossRefPubMedGoogle Scholar
  154. Vennarecci G, Kato T, Misiakos E, et al (2000) Intestinal transplantation for short gut syndrome attributable to necrotizing enterocolitis. Pediatrics 2(105):587–595Google Scholar
  155. Voganatsi A et al (2001) Mechanism of extracellular release of human neutrophil calprotectin complex. J Leukoc Biol 70(1):130–134PubMedGoogle Scholar
  156. Walsh M, Kliegman R (1986) Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 33(1):179–210CrossRefGoogle Scholar
  157. 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 of 20 randomized, controlled trials. J Pediatr Surg 47(1):241–248.  https://doi.org/10.1016/j.jpedsurg.2011.09.064CrossRefPubMedGoogle Scholar
  158. Wang M, Li M, Wu S, Lebrilla C, Chapkin R, Ivanov I, Donovan S (2015) Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr 60(6):825.  https://doi.org/10.1097/MPG.0000000000000752CrossRefPubMedPubMedCentralGoogle Scholar
  159. Yatsunenko T, Rey F, Manary M, et al (2012) Human gut microbiome viewed across age and geography. Nature 7402(486). http://www.ncbi.nlm.nih.gov/pubmed/22699611. Accessed 28 Sept 2015
  160. Yoon JM, Min J, Yi J et al (2014) Fecal calprotectin concentration in neonatal necrotizing enterocolitis. Korean J Pediatr 57(8):351.  https://doi.org/10.3345/kjp.2014.57.8.351CrossRefPubMedPubMedCentralGoogle Scholar
  161. Zoppelli L, Güttel C, Bittrich H-J, Andrée C, Wirth S, Jenke A (2012) Fecal calprotectin concentrations in premature infants have a lower limit and show postnatal and gestational age dependence. Neonatology 102(1):68–74.  https://doi.org/10.1159/000337841CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of NeonatologyUniversity of Florida, College of MedicineGainesvilleUSA

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