Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1988;33(Suppl 3):78S–84S. doi: 10.1007/BF01538135

Neonatal necrotizing enterocolitis

Inflammatory bowel disease of the newborn

David P Cheromcha 1, Paul E Hyman 1,✉
PMCID: PMC7087600  PMID: 3126029

Abstract

Neonatal necrotizing enterocolitis is the most common serious gastrointestinal disorder encountered in neonatal intensive care units. It is a major cause of morbidity and mortality in the newborn, particularly in premature infants. Consistent risk factors are birth weight and prematurity. Polycythemia and hyperviscosity altering blood flow and infectious agents are also implicated. Clinical findings include abdominal distention and diarrhea, and systemic symptoms such as apnea, acidosis, and lethargy. Pneumatosis intestinalis can be demonstrated radiographically. Mucosal ulcerations, hemorrhage, and thrombosis occur early, followed by inflammatory changes. Later still necrosis develops. Ischemia, infection, and enteral feedings are suspected to be involved in the pathophysiology. Eicosanoids, especially thromboxane, platelet-activating factor, and leukotrienes are likely mediators.

Key words: necrotizing enterocolitis, premature infants, neonate, thromboxane

References

  • 1.Ryder RW, Shelton JD, Guinan ME. Necrotizing enterocolitis: A prospective multicenter investigation. Am J Epidemiol. 1980;112:113–123. doi: 10.1093/oxfordjournals.aje.a112960. [DOI] [PubMed] [Google Scholar]
  • 2.Kanto WP, Wilson R, Breart GL, Zierlers S, Purohit OM, Peckham GJ, Ellison RC. Perinatal events and necrotizing enterocolitis in premature infants. Am J Dis Child. 1987;141:167–169. doi: 10.1001/archpedi.1987.04460020057026. [DOI] [PubMed] [Google Scholar]
  • 3.Stoll BJ, Kano WP, Glass RI, Nahmias AJ, Brannon AW. Epidemiology of necrotizing entercolitis: A case-control study. J Pediatr. 1980;96:447–451. doi: 10.1016/s0022-3476(80)80696-2. [DOI] [PubMed] [Google Scholar]
  • 4.Kleigman RM, Fanaroff AA. Neonatal necrotizing enterocolitis: A nine-year experience. Am J Dis Child. 1981;135:603–607. doi: 10.1001/archpedi.1981.02130310009005. [DOI] [PubMed] [Google Scholar]
  • 5.Polin RA, Pollack PF, Barlow B, Wigger JH, Slovis TL, Santulli TU, Heiro WC. Necrotizing enterocolitis in term infants. J Pediatr. 1976;89:460–462. doi: 10.1016/s0022-3476(76)80551-3. [DOI] [PubMed] [Google Scholar]
  • 6.Kleigman RM, Hack M, Jones P, Fanaroff AA. Epidemiological study of necrotizing enterocolitis among low-birth-weight infants. J Pediatr. 1982;100:440–444. doi: 10.1016/s0022-3476(82)80456-3. [DOI] [PubMed] [Google Scholar]
  • 7.Bauer CR, Morrison JC, Poole WR, Korones SB, Boehm JJ, Rigatto H, Zachman RD. A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy. Pediatrics. 1984;73:682–687. [PubMed] [Google Scholar]
  • 8.Collaborative Group on Antenatal Steroid Therapy Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol. 1984;141:276–287. [PubMed] [Google Scholar]
  • 9.Wilson R, delPortillo M, Schmidt E, Feldman RA, Kanto WP., Jr Risk factors for necrotizing enterocolitis in infants weighing more than 2000 grams at birth: A case-control study. Pediatrics. 1983;71:19–21. [PubMed] [Google Scholar]
  • 10.Moomjian A, Peckham G, Fox W, Pereira GR, Schaberg DA. Necrotizing enterocolitis endemic vs epidemic form. Pediatr Res. 1978;12:5530. [Google Scholar]
  • 11.Gregory JR, Campbell JR, Harrison MW, Campbell TJ. Neonatal necrotizing enterocolitis: A 10-year experience. Am J Surg. 1987;141:562–567. doi: 10.1016/0002-9610(81)90049-0. [DOI] [PubMed] [Google Scholar]
  • 12.Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis: Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–6. doi: 10.1097/00000658-197801000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Benirschke K. NEC in the newborn infant: Report of 68th Ross Conference on Pediatric Research. Columbus, Ohio: Ross Laboratories; 1974. p. 27. [Google Scholar]
  • 14.Arnon RG, Fishbein JF. Portal venous gas in the pediatric age group. J Pediatr. 1971;79:255–259. doi: 10.1016/s0022-3476(71)80110-5. [DOI] [PubMed] [Google Scholar]
  • 15.Leonard T, Johnson A, Pettet PG. Critical evaluation of the persistent loop sign in necrotizing enterocolitis. Radiology. 1982;142:385–386. doi: 10.1148/radiology.142.2.7054826. [DOI] [PubMed] [Google Scholar]
  • 16.Santelli TV, Schullinger JN, Haird WC, Gongaware RD, Wigger J, Barlow B, Blanc W, Berdon WE. Acute necrotizing enterocolitis in infancy: A review of 64 cases. Pediatrics. 1975;55:376–387. [PubMed] [Google Scholar]
  • 17.Touloukian RJ, Posch JN, Spencer R. The pathogenesis of ischemic gastroenteritis of the neonate: Selective gut mucosal ischemia in asphyxiated neonatal piglets. J Pediatr Surg. 1972;7:194–207. doi: 10.1016/0022-3468(72)90496-4. [DOI] [PubMed] [Google Scholar]
  • 18.Lloyd JR. The etiology of gastrointestinal perforation in the newborn. J Pediatr Surg. 1969;4:77–84. doi: 10.1016/0022-3468(69)90186-9. [DOI] [PubMed] [Google Scholar]
  • 19.Brady P, Garik T, German J. Fetal heart rate patterns in infants in whom necrotizing enterocolitis develops. Arch Surg. 1980;115:1050. doi: 10.1001/archsurg.1980.01380090030008. [DOI] [PubMed] [Google Scholar]
  • 20.Yu VY, Tudehope DI. Neonatal necrotizing enterocolitis II. Perinatal risk factors. Med J Aust. 1977;1:688. doi: 10.5694/j.1326-5377.1977.tb131029.x. [DOI] [PubMed] [Google Scholar]
  • 21.Virnig NZ, Reynolds JW. Epidemiological aspects of neonatal necrotizing enterocolitis. Am J Dis Child. 1974;128:186–190. doi: 10.1001/archpedi.1974.02110270060012. [DOI] [PubMed] [Google Scholar]
  • 22.Tyson JE, deSa DJ, Moore S. Thromboartheromatous complications of umbilical arterial catheterization in the newborn period. Arch Dis Child. 1976;51:744–754. doi: 10.1136/adc.51.10.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Bunton GL, Durbin GM, McIntosh N, Shaw DG, Taghizadeh A, Reynolds EOR, Rivers RPA, Urman G. Necrotizing enterocolitis: Controlled study of 3 years' experience in a neonatal intensive care unit. Arch Dis Child. 1977;52:772–777. doi: 10.1136/adc.52.10.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Kliegman R, Stork E, Fanaroff A. Lack of relationship between umbilical arterial catheter complications and necrotizing enterocolitis. Pediatr Res. 1985;19:349A. [Google Scholar]
  • 25.Leake RD, Thanopoulos B, Nieberg R. Hyperviscosity syndrome associated with necrotizing enterocolitis. Am J Dis Child. 1975;129:1192–1194. doi: 10.1001/archpedi.1975.02120470042011. [DOI] [PubMed] [Google Scholar]
  • 26.Le Blanc MH, D'Cruz C, Pate K. Necrotizing enterocolitis can be caused by polycythemic hyperviscosity in the new-born dog. J Pediatr. 1984;105:804–808. doi: 10.1016/s0022-3476(84)80311-x. [DOI] [PubMed] [Google Scholar]
  • 27.Kliegman RM. Neonatal necrotizing enterocolitis: Implications for an infectious disease. Pediatr Clin North Am. 1979;26:327–344. doi: 10.1016/s0031-3955(16)33709-9. [DOI] [PubMed] [Google Scholar]
  • 28.Book LS, Overall JUC, Herbst JJ, Britt MR, Epstein B, Jung AL. Clustering of necrotizing enterocolitis: Interruption by infection-control measures. N Engl J Med. 1977;297:984–986. doi: 10.1056/NEJM197711032971805. [DOI] [PubMed] [Google Scholar]
  • 29.Cushion AH. Necrotizing enterocolitis ofEscherichia coli: Heat-labile enterotoxin. Pediatrics. 1983;71:626–630. [PubMed] [Google Scholar]
  • 30.Hill HR, Hunt CE, Matsen JM. Nocosomial colonization with klebsiella type 26, in a neonatal intensive care unit associated with an outbread of sepsis, meningitis and necrotizing enterocolitis. J Pediatr. 1974;85:415–449. doi: 10.1016/s0022-3476(74)80133-2. [DOI] [PubMed] [Google Scholar]
  • 31.Powell J, Bureau M, Pare C, Galiory ML, Cabana D, Patriquin H. Necrotizing enterocolitis: epidemic following an outbreak of enterobacter cloaca. Am J Dis Child. 1980;134:1152–1154. [PubMed] [Google Scholar]
  • 32.Chany C, Mostovici O, Lebon P, Rousset S. Association of coronavirus with neonatal necrotizing enterocolitis. Pediatrics. 1982;69:209–218. [PubMed] [Google Scholar]
  • 33.Anderson C, Collin M, Okeefe J. A widespread epidemic of mild necrotizing enterocolitis of unknown cause. Am J Dis Child. 1984;138:979. doi: 10.1001/archpedi.1984.02140480081025. [DOI] [PubMed] [Google Scholar]
  • 34.Lawrence G, Bates J, Gal A. Pathogenesis of necrotizing enterocolitis. Lancet. 1982;1:137–139. doi: 10.1016/s0140-6736(82)90383-x. [DOI] [PubMed] [Google Scholar]
  • 35.Cashore WJ, Peter G, Lauermann M, Stonestreet BS, Oh W. Clostridial colonization and clostridial toxin in neonatal necrotizing enterocolitis. J Pediatr. 1981;98:308–311. doi: 10.1016/s0022-3476(81)80667-1. [DOI] [PubMed] [Google Scholar]
  • 36.Yale CE, Balish E. The importance of six common bacteria in intestinal strangulation. Arch Surg. 1972;107:438–442. doi: 10.1001/archsurg.1972.04180040052009. [DOI] [PubMed] [Google Scholar]
  • 37.Yale CE, Balish E, Wu JP. The bacterial etiology of pneumotosis cystoides intestinalis. Arch Surg. 1974;109:89. doi: 10.1001/archsurg.1974.01360010067017. [DOI] [PubMed] [Google Scholar]
  • 38.Barlow B, Santulli TV, Heird WA, Pitt J, Blanc WA, Schullinger JN. An experimental study of acute neonatal enterocolitis-the importance of breast milk. J Pediatr Surg. 1974;9:587–594. doi: 10.1016/0022-3468(74)90093-1. [DOI] [PubMed] [Google Scholar]
  • 39.Kliegman RM, Pittard WE, Fanakroff AA. Necrotizing enterocolitis in neonates fed human milk. J Pediatr. 1979;95:450–453. doi: 10.1016/s0022-3476(79)80534-x. [DOI] [PubMed] [Google Scholar]
  • 40.Book LS, Herbst JJ, Atherton SO, Jung AL. Necrotizing enterocolitis in low-birth-weight infants fed an elemental formula. J Pediatr. 1975;87:602–605. doi: 10.1016/s0022-3476(75)80835-3. [DOI] [PubMed] [Google Scholar]
  • 41.Goldman HI. Feeding and necrotizing enterocolitis. AM J Dis Child. 1980;134:553–555. doi: 10.1001/archpedi.1980.02130180011004. [DOI] [PubMed] [Google Scholar]
  • 42.Osterrag SG, LaGamma EF, Reisen CE, Ferrentino FL. Early enteral feeding does not affect the incidence of necrotizing enterocolitis. Pediatrics. 1987;77:275–280. [PubMed] [Google Scholar]
  • 43.deLemos RA, Rogers JH, McLaughlin GW. Experimental production of necrotizing enterocolitis in newborn goats. Pediatr Res. 1974;8:380. [Google Scholar]
  • 44.Willis DM, Chabot J, Raddle IC, Chance GW. Unsuspected hyperosmolarity of oral solutions contributing to necrotizing enterocolitis in very-low-birth-weight infants. Pediatrics. 1977;60:535–538. [PubMed] [Google Scholar]
  • 45.Brown EG, Sweet AY. Preventing necrotizing enterocolitis in neonates. JAMA. 1978;240:2452–2454. [PubMed] [Google Scholar]
  • 46.Murrell TJC, Roth L. Necrotizing jejunitis: A newly discovered disease in the highlands of New Guinea. Med J Aust. 1963;1:68. doi: 10.5694/j.1326-5377.1963.tb27120.x. [DOI] [PubMed] [Google Scholar]
  • 47.Nowicki PT, Stonestreet BS, Hansen NB, Yao AC, Oh W. Gastrointestinal blood flow and oxygen consumption in awake newborn piglets: Effects of feeding. Am J Physiol. 1983;245:G697–G702. doi: 10.1152/ajpgi.1983.245.5.G697. [DOI] [PubMed] [Google Scholar]
  • 48.Engel R. Necrotizing enterocolitis in the newborn: Report of 68th Ross Conference on Pediatric Research. Columbus, Ohio: Ross Laboratories; 1974. pp. 66–71. [Google Scholar]
  • 49.Book LS, Herbst JJ, Jung AL. Comparison of fast- and slow-feeding rate schedules to the development of necrotizing enterocolitis. J Pediatr. 1976;89:463–466. doi: 10.1016/s0022-3476(76)80552-5. [DOI] [PubMed] [Google Scholar]
  • 50.LaGamma EF, Ostertag SG, Birenbaum H. Delayed feeding fails to prevent necrotizing enterocolitis. Am J Dis Child. 1985;139:385–389. doi: 10.1001/archpedi.1985.02140060067031. [DOI] [PubMed] [Google Scholar]
  • 51.Anysley-Green A. Hormones and postnatal adaptation to enterai nutrition. J Pediatr Gastroenterol Nutr. 1983;2:418. doi: 10.1097/00005176-198302030-00005. [DOI] [PubMed] [Google Scholar]
  • 52.Hyman PE, Abrams CE, Zipser RD. Enhanced urinary immunoreactive thromboxane in neonatal necrotizing enterocolitis: A diagnostic indicator of thrombotic activity. Am J Dis Child. 1987;141:686–689. doi: 10.1001/archpedi.1987.04460060102046. [DOI] [PubMed] [Google Scholar]
  • 53.Gonzalez-Guzzi F, Hsueh W. Experimental model of ischemic bowel necrosis. The role of platelet activating factor and endotoxin. Am J Pathol. 1983;112:127–135. [PMC free article] [PubMed] [Google Scholar]
  • 54.Hsueh W, Gonzalez-Crussi F, Arroyave JL. Platelet-activating factor-induced ischemic bowel necrosis. Am J Pathol. 1986;122:231–239. [PMC free article] [PubMed] [Google Scholar]
  • 55.Hseuh W, Gonzales-Crussi F, Arroyave JL. Release of leukotriene C4 by isolated perfused rat small intestine in response to platelet-activating factor. J Clin Invest. 1986;78:108–114. doi: 10.1172/JCI112538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Clark DA, Pelley RP, Schneider AJ. Interaction between bovine casein andV. cholera enterotoxin in the rabbit ileal loop. Pediatr Res. 1983;17:1008–1012. doi: 10.1203/00006450-198312000-00016. [DOI] [PubMed] [Google Scholar]
  • 57.Clark DA, Thompson JE, Weiner LB, Micmillian JA, Schneider AJ, Rokahr JE. Necrotizing enterocolitis: Intraluminal biochemistry in human neonates and a rabbit model. Pediatr Res. 1985;19:919–921. doi: 10.1203/00006450-198509000-00010. [DOI] [PubMed] [Google Scholar]
  • 58.Clark DA, Mullane K, Caravella S, McNeill H, Dweck HS, Miller MJS. Eicosanoid and leukocyte participation in experimental necrotizing enterocolitis. Pediatr Res. 1987;21:407. [Google Scholar]

Articles from Digestive Diseases and Sciences are provided here courtesy of Nature Publishing Group

RESOURCES