New Nutritional and Therapeutical Strategies of NEC

Author(s): Capriati Teresa*, Diamanti Antonella, de Ville de Goyet Jean

Journal Name: Current Pediatric Reviews

Volume 15 , Issue 2 , 2019

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Necrotizing enterocolitis (NEC) is an acquired severe disease of the digestive system affecting mostly premature babies, possibly fatal and frequently associated to systemic complications. Because of the severity of this condition and the possible long-term consequences on the child’s development, many studies have aimed at preventing the occurrence of the primary events at the level of the bowel wall (ischemia and necrosis followed by sepsis) by modifying or manipulating the diet (breast milk versus formula) and/or the feeding pattern (time for initiation after birth, continuous versus bolus feeding, modulation of intake according clinical events). Feeding have been investigated so far in order to prevent NEC. However, currently well-established and shared clinical nutritional practices are not available in preventing NEC. Nutritional and surgical treatments of NEC are instead well defined. In selected cases surgery is a therapeutic option of NEC, requiring sometimes partial intestinal resection responsible for short bowel syndrome. In this paper we will investigate the available options for treating NEC according to the Walsh and Kliegman classification, focusing on feeding practices in managing short bowel syndrome that can complicate NEC. We will also analyze the proposed ways of preventing NEC.

Keywords: Necrotizing enterocolitis, preterm infants, enteral nutrition, parenteral nutrition, surgical treatment, prevention.

Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CA, Schonberger LB. Necrotisingenterocolitishospitalisations among neonates in the United States. Paediatr Perinat Epidemiol 2006; 20(6): 498-506.
Christensen RD, Gordon PV, Besner GE. Can we cut the incidence of necrotizing enterocolitis in half e today? Fetal Pediatr Pathol 2010; 29: 185e98.
Lambert DK, Christensen RD, Henry E, et al. Necrotizing enterocolitis in term neonates: Data from a multihospital health-care system. J Perinatol 2007; 27: 437e43.
Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003; 23(278e85)
Blakely ML, Gupta H, Lally KP. Surgical management of necrotizing enterocolitis and isolated intestinal perforation in premature neonates. Semin Perinatol 2008; 32: 122e6.
Hintz SR, Kendrick DE, Stoll BJ, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005; 115: 696e703.
Bell MJ. Neonatal necrotizing enterocolitis. N Engl J Med 1978; 298: 281-2.
Walsh MC, Kliegman RM. Necrotizing enterocolitis: Treatment based on staging criteria. Pediatr Clin North Am 1986; 33(1): 179-201.
Fanaroff AA, Stoll BJ, Wright LL, et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 2007; 196: 147.e1-8.
Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol 1994; 21: 205-18.
Lee JS, Polin RA. Treatment and prevention of necrotizing enterocolitis. Semin Neonatol 2003; 8: 449-59.
Carter B. Treatment outcomes of necrotizing enterocolitis for preterm infants. J Obstet Gynecol Neonatal Nurs 2006; 36: 377-85.
Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2001; 2CD000503
Stritzke AI, Smyth J, Synnes A, Lee SK, Shah PS. Transfusion associated necrotisingenterocolitis in neonates.Arch Dis Child Fetal Neonatal Ed. 2013; 98: p. F10e4.
Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: A meta-analysis of observational data. Pediatrics 2012; 129: 529e40.
Anand RJ, Leaphart CL, Mollen KP, Hackam DJ. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis Shock 2007; 27: 124e33.
Chan KL, Saing H, Yung RW, Tsoi NS. A study of preantibiotic bacteriology in 125 patients with necrotizing enterocolitis. Acta Paediatr Suppl 1994; 396: 45-8.
Gill CJ, Pallasch TJ. Clindamycin-associated pseudomembranous colitis: a potentially fatal adverse drug reaction. J Am Dent Assoc 1981; 102: 507-9.
Faix RG, Polley TZ, Grasela TH. A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. J Pediatr 1988; 112: 271-7.
Fallon EM, Nehra D, Potemkin AK, Gura KM, Simpser E, Compher CASPEN. Clinical guidelines: Nutrition support of neonatal patients at risk for Necrotizing Enterocolitis. J Parenter Enteral Nutr 2012; 36(5): 506-23.
Brotschi B, Baenziger O, Frey B, Bucher HU, Ersch J. Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J Perinat Med 2009; 37(6): 701-5.
Bohnhorst B, Muller S, Dordelmann M, Peter CS, Petersen C, Poets CF. Early feeding after necrotizing enterocolitis in preterm infants. J Pediatr 2003; 143(4): 484-7.
Kim WY, Kim WS, Kim IO, Kwon TH, Chang W, Lee EK. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr Radiol 2005; 35: 1056-61.
Anand KJ. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001; 155: 173-80.
Anand KJ, Aranda JV, Berde CB, et al. Summary proceedings from the neonatal pain-control group. Pediatrics 2006; 117(3 Pt 2): S9-S22.
Willis DM, Chabot J, Radde IC, Chance GW. Unsuspected hyperosmolality of oral solutions contributing to necrotizing enterocolitis in very-low-birth-weight infants. Pediatrics 1977; 60: 535-8.
Franck LS, Naughton I, Winter I. Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care patients. Intensive Crit Care Nurs 2004; 20: 344-51.
Franck LS, Miaskowski C. The use of intravenous opioids to provide analgesia in critically ill, premature neonates: A research critique. J Pain Symptom Manage 1998; 15: 41-69.
Ein SH, Marshall DG, Girvan D. Peritoneal drainage under local anesthesia for perforationsfrom necrotizing enterocolitis. J Pediatr Surg 1977; 12(6): 963-7.
Federici S, De Biagi L, Straziuso S, et al. Multicenter retrospective study of management and outcome of newborns affected by surgical necrotizing enterocolitis. Minerva Chirurgica 2017; 72(3): 183-7.
Hull MA, Fisher JG, Gutierrez IM, et al. Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: A prospective cohort study. J Am Coll Surg 2014; 218(6): 1148-55.
Eicher C, Seitz G, Bevot A, et al. Surgical management of extremely low birth weight infants with neonatal bowel perforation: A single-center experience and a review of the literature. Neonatology 2012; 101(4): 285-92.
Tepas III J.J., Sharma R, Hudak ML, Garrison RD, Pieper P. Coming full circle: an evidence-based definition ofthe timing and type of surgical management ofvery low-birth-weight (<1000 g) infants with signs of acute intestinal perforation. J Pediatr Surg 2006; 41(2): 418-22.
Chiu B, Pillai SB, Almond PS, et al. To drain or not to drain: A single institution experience with neonatal intestinal perforation. J Perinat Med 2006; 34(4): 338-41.
Romero RM, Garcìa-Casillas AA, Matule JA, et al. Role of peritoneal drenage in very low birth weight with enterocolitis. Cir Pediatr 2005; 18(2): 88-92.
Zenciroğlu A, Cakmak O, Demirel N, et al. Outcome of primary peritoneal drainage for perforated necrotizing enterocolitis: Comparison between laparotomy and drainage. Eur J Pediatr Surg 2005; 15(4): 243-7.
Roy A, Tayeb M, Al-Khogeer S. Outcome in definite and advanced neonatal necrotizing enterocolitis. Saudi Med J 2004; 25(6): 746-52.
Ehrlich PF, Sato TT, Short BL, Hartman GE. Outcome of perforated necrotizing enterocolitis in the very low-birth weight neonate may be independent of the type of surgical treatment. Am Surg 2001; 67(8): 752-6.
Noble HGS, Driessnack M. Bedside peritoneal drainage in very low birth weight infants. The Am J Surg 2001; 181(5): 416-9.
Dimmitt RA, Meier AH, Skarsgard ED, Halamek LP, Smith BM, Moss RL. Salvage laparotomy for failure of peritoneal drainage in necrotizing enterocolitis in infants with extremely low birth weight. J Pediatr Surg 2000; 35(6): 856-9.
Moss RL, Dimmitt RA, Barnhart DC, et al. Laparotomy versus peritoneal drainage fornecrotizingenterocolitis and perforation. N Engl J Med 2006; 354(21): 2225-34.
Rees CM, Eaton S, Kiely EM, Wade AM, McHugh K, Pierro A. Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial. Ann Surg 2008; 248(1): 44-51.
Rees CM, Eaton S, Khoo AK, Kiely EM. Members of NET Trial Group Pierro A. Peritoneal drainage does not stabilize extremely low birth weight infants with perforated bowel: data from the NET Trial. J Pediatr Surg 2010; 45: 324-8.
Rao SC, Basani L, Simmer K, Samnakay N, Deshpande G. 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 2011; 6(6)CD006182
Blakely ML, Tyson JE, Lally KP, et al. NICHD Neonatal Research Network. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: Outcomes through 18 mo adjusted age. Pediatrics 2006; 117: e680-7.
Sola JE, Tepas JJ 3rd, Koniaris LG. Peritoneal drainage versus Laparotomy for Necrotizing enterocolitis and intestinal perforation: A meta-analysis. J Surg Res 2010; 161: 95-100.
Ta BD, Roze E, van Breckel KN, Bos AF, Rassouli-Kirchmeier R, Hulscher JB. Long-termneurodevelopmental impairment in neonates surgically treated for necroizingenterocolitis: Enterostomy associated with a worse outcome. Eur J Pediatr Surg 2011; 21(1): 58-64.
Ehtayeb AA, Mostafa MM, Ibrahim NH, Elthayeb AA. The role of surgery in management of necrotizing enterocolitis. Int J Surgery 2010; 8(6): 458-61.
Hall NJ, Curry J, Drake DP, Spitz L, Kiely EM, Pierro A. Resection and primary anastomosis is a valid surgical option for infant with necrotizing enterocolitis who weigh less than 1000 g. Arch Surg 2005; 140(12): 1149-51.
Hofman FN, Bax NM, van der Zee DC, Kramer WL. Surgery for necrotizing enterocolitis: Primary anastomosis or enterostomy? Pediatr Surg Int 2004; 20(7): 481-3.
Downard CD, Renaud E, St. Peter SD, et al. Treatment of necrotizing enterocolitis: An American pediatric surgical association outcomes and clinical trials Committee systematic review. J Pediatr Surg 2012; 47: 2111-22.
Barclay AR1, Beattie LM, Weaver LT, Wilson DC. Systematic review: Medical and nutritional interventions for the management of intestinal failure and its resultant complications in children. Aliment Pharmacol Ther 2011; 33(2): 175-84.
D’Antiga L, Goulet O. Intestinal failure in children: The European view. JPGN 2013; 56: 118-26.
Kocoshis SA. Medical management of pediatric intestinal failure. Semin Pediatr Surg 2010; 19: 20-6.
Pironi L, Joly F, Forbes A, et al. Long-term follow-up of patients on home parenteral nutrition in Europe: Implications for intestinal transplantation. Gut 2011; 60: 17-25.
Dalzell AM. Management of intestinal failure in children. Arch Dis Child 201; 100(10): 980-3.
Goulet O, Olieman J, Ksiazyk J, et al. Neonatal short bowel syndrome as a model of intestinal failure: Physiological background for enteral feeding. Clin Nutr 2013; 32: 162-71.
Koletzko B, Goulet O, Hunt J, Krohn K, Shamir R. Guidelines on paediatric parenteral nutrition of the european society of paediatric gastroenterology, hepatology and nutrition (ESPGHAN) and the European society for clinical nutrition and metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005; (41): (Suppl. 2)S1-S87.
Tillman EM. Review and clinical update on parenteral nutrition-associated liver disease. Nutr Clin Pract 2013; 28(1): 30-9.
Rangel SJ, Calkins CM, Cowles RA, et al. Parenteral nutrition-associated cholestasis: An American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg 2012; 47(1): 225-40.
Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 2000; 132: 525-32.
Wanten GJ. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble? J Parenter Enteral Nutr 2015; 39(1)(Suppl.): 33S-8S.
Gura KM, Lee S, Valim C, et al. Safety and efficacy of a fish-oil–based fat emulsion in the treatment of parenteral nutrition–associated liver disease. Pediatrics 2008; 121(3): e678-86.
Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm: Omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009; 48(2): 209-15.
Lee S, Park HJ, Yoon J, et al. Reversal of intestinal failure–associated liver disease by switching from a combination lipid emulsion containing fish oil to fish oil monotherapy. J Parenter Enteral Nutr 2016; 40(3): 437-40.
Goulet O, Antebi H, Wolf C, et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2010; 34: 485-95.
Forchielli ML, Miller SJ. Nutritional goals and requirements. In: Merritt R, Ed The ASPEN Nutrition Support Practice Manual. 2nd ed. Silver Spring, MD: A.S.P.E.N. 2005; pp. 38-53.
Kleinman RE. Parenteral nutrition. In: Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL: American Academy of Pediatrics 2009; pp. 519-40.
Jakobsen MS, Jørgensen MH, Husby S, Andersen L, Jeppesen PB. Low-Fat, High-Carbohydrate Parenteral Nutrition (PN) may potentially reverse liver disease in long-term PN-Dependent Infants. Dig Dis Sci 2015; 60(1): 252-9.
Byars KC, Burklow KA, Ferguson K, O’Flaherty T, Santoro K, Kaul A. A multicomponent behavioral program for oral aversion in children dependent on gastrostomy feedings. J Pediatr Gastroenterol Nutr 2003; 37(4): 473-80.
Andorsky DJ, Lund DP, Lillehei CW, et al. Nutritional and other post operative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr 2001; 139(1): 27-33.
Lundqvist-Persson C, Lau G, Nordin P, Strandvik B, Sabel KG. Early behaviour and development in breast-fed premature infants are influenced by omega-6 and omega-3 fatty acid status. Early Hum Dev 2010; 86(7): 407-12.
Underwood MA. Human milk for the premature infant. Pediatr Clin North Am 2013; 60(1): 189-207.
Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature 2011; 474(7351): 327-36.
Roger LC, McCartney AL. Longitudinal investigation of the faecalmicrobiota of healthy full-term infants using fluorescence in situ hybridization and denaturing gradient gel electrophoresis. Microbiology 2010; 156(Pt11): 3317-28.
Sangild PT. Gut responses to enteral nutrition in preterm infants and animals. Exp Biol Med (Maywood) 2006; 231(11): 1695-711.
Diamanti A, Fiocchi AG, Capriati T, et al. Cow’s milk allergy and neonatal short bowel syndrome: comorbidity or true association? Eur J Clin Nutr 2015; 69(1): 102-6.
Jeppesen PB, Mortensen PB. The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection. Gut 1998; 43(4): 478-83.
Steele JR, Meskell RJ, Foy J, Garner AE. Determining the osmolality of over concentrated and supplemented infant formulas. J Hum Nutr Diet 2013; 26(1): 32-7.
Di Lorenzo C1. Youssef NN. Diagnosis and management of intestinal motility disorders. Seminars in Pediatric Surgery 2010; 19(1): 50-8.
Benjamin J, Singh N, Makharia GK. Enteral nutrition for severe malnutrition in chronic intestinal pseudo-obstruction. Nutrition 2010; 26(5): 502-5.
Kaufman SS, Matsumoto CS. Management of pediatric intestinal failure. Minerva Pediatr 2015; 67(4): 321-40.
Gariepy CE, Mousa H. Clinical management of motility disorders in children. Semin Pediatr Surg 2009; 18(4): 224-38.
Cole CR, Kocoshis SA. Nutrition management of infants with surgical short bowel syndrome and intestinal failure. Nutr Clin Pract 2013; 28(4): 421-8.
Booth IW, Lander AD. Short bowel syndrome. Baillieres Clin Gastroenterol 1998; 12(4): 739-73.
Nightingale JM, Lennard-Jones JE, Gertner DJ, Wood SR, Bartram CI. Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gall stones in patients with a short bowel. Gut 1992; 33(1): 1493-7.
DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol 2004; 99(7): 1386-95.
Goulet O, Ruemmele F, Lacaille F, Colomb V. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 2004; 38(3): 250-69.
Colomb V, Ricour C. Home parenteral nutrition in children. Clin Nutr 2003; 22(Suppl. 2): S57-9.
Schanler RJ, Lau C, Hurst NM, Smith EO. Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics 2005; 116(2): 400-6.
McGuire W, Anthony MY. Donor human milk versus formula for preventing necrotisingenterocolitis in preterm infants: Systematic review. Arch Dis Child Fetal Neonatal Ed 2003; 88(1): F11-4.
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
Patole S. Strategies for prevention of feed intolerance in preterm neonates: a systematic review. J Matern Fetal Neonatal Med 2005; 8(1): 67-76.
Berseth CL. Feeding strategies and necrotizing enterocolitis. Curr Opin Pediatr 2005; 17(2): 170-3.
Lucas A, Cole TJ. Breast milk and neonatal necrotisingenterocolitis. Lancet 1990; 336(8730): 1519-23.
McClure RJ. Trophic feeding of the preterm infant. Acta Paediatr Suppl 2001; 90(436): 19-21.
Newell SJ. Enteral feeding of the micropremie. Clin Perinatol 2000; 27(1): 221-34.
Bombell S, McGuire W. Early trophic feeding for very low birth weight infants. Cochrane Database Syst Rev 2009; (3): CD000504
Anderson DM, Kliegman RM. The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis. Am J Perinatol 1991; 8(1): 62-7.
Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotisingenterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2011; (3): CD001970
Patole SK, de Klerk N. Impact of standardised feeding regimens on incidence of neonatal necrotisingenterocolitis: A systematic review and meta-analysis of observational studies. Arch Dis Child Fetal Neonatal Ed 2005; 90(2): F147-51.
Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotisingenterocolitis in very low birth weight infants in very low birth weight infants. Cochrane Database Syst Rev 2011; (3): CD001241
Dutta S, Singh B, Chessell L, et al. Guidelines for Feeding Very Low Birth Weight Infants. Nutrients 2015; 7(1): 423-42.
Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005; 128(1): 175-91.
Aynsley-Green A, Adrian TE, Bloom SR. Feeding and the development of enteroinsular hormone secretion in the preterm infant: effects of continuous gastric infusions of human milk compared with intermittent boluses. Actapaediatrica Scandinavica 1982; 71(3): 379-83.
Premji SS, Chessell L. Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. Cochrane Database Syst Rev 2011; (11): CD001819
Cobb BA, Carlo WA, Ambalavanan N. Gastric residuals and their relationship to necrotizing enterocolitis in very low birth weight infants. Pediatrics 2004; 113(1 Pt 1): 50-3.
Terrin G, Passariello A, Canani RB, Manguso F, Paludetto R, Cascioli C. Minimal enteral feeding reduces the risk of sepsis in feed-intolerant very low birth weight newborns. Acta Paediatr 2009; 98(1): 31-5.
Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting growth in preterm infants. Cochrane Database Syst Rev 2004; (1): CD000343
Sullivan S, Schanler RJ, Kim JH, 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(4): 562-7.
Pearson F, Johnson MJ, Leaf AA. Milk osmolality: Does it matter? Arch Dis Child Fetal Neonatal Ed 2013; 98(2): F166-9.
Commentary on breast-feeding and infant formulas, including proposed standards for formulas. Pediatrics 1976; 57(2): 278-85.
Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol 2013; 45(8): 1730-47.
Siggers RH, Siggers J, Thymann T, Boye M, Sangild PT. Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis. J Nutr Biochem 2011; 22(6): 511-21.
Jensen ML, Sangild PT, Lykke M, et al. Similar efficacy of human banked milk and bovine colostrum to decrease incidence of necrotizing enterocolitis in preterm piglets. Am J Physiol Regul Integr Comp Physiol 2013; 305(1): R4-R12.
Shen RL, Thymann T, Østergaard MV. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs. Am J Physiol Gastrointest Liver Physiol 2015; 309(5): G310-23.
Li Y, Juhl SM, Ye X, et al. A stepwise, Pilot Study of bovine colostrum to supplement the first enteral feeding in preterm infants (Precolos): Study protocol and initial results. Front Pediatr 2017; 3;5: 42.
Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem 2004; 15(8): 442-51.
Ziegler TR, Evans ME, Fernandez-Estivariz C, Jones DP. Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Annu Rev Nutr 2003; 23: 229-61.
Domeneghini C, Di Giancamillo A, Arrighi S, Bosi G. Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism. State of the art in the pig, and perspectives towards humans. Histol Histopathol 2006; 21(3): 273-83.
Becker RM, Wu G, Galanko JA, et al. Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 2000; 137(6): 785-93.
Celik IH, Demirel G, Canpolat FE, Dilmen U. Reduced plasma citrulline levels in low birth weight infants with necrotizing enterocolitis. J Clin Lab Anal 2013; 27(4): 328-32.
Richir MC, Siroen MP, van Elburg RM, et al. Low plasma concentrations of arginine and asymmetric dimethylarginine in premature infants with necrotizing enterocolitis. Br J Nutr 2007; 97(5): 906-11.
Di Lorenzo M, Bass J, Krantis A. Use of L-arginine in the treatment of experimental necrotizing enterocolitis. J Pediatr Surg 1995; 30(2): 235-40.
Akisu M, Ozmen D, Baka M, et al. Protective effect of dietary supplementation with L-arginine and L-carnitine on hypoxia/reoxygenationinduced necrotizing enterocolitis in young mice. Biol Neonate 2002; 81(4): 260-5.
Puiman PJ, Stoll B, van Goudoever JB, et al. Enteral arginine does not Increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs. J Nutr 2011; 141(1): 63-70.
Amin HJ, Zamora SA, McMillan DD, et al. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr 2002; 140(4): 425-31.
Polycarpou E, Zachaki S, Tsolia M, et al. Enteral L-arginine supplementation for prevention of necrotizing enterocolitis in very low birth weight neonates: A double-blind randomized pilot study of efficacy and safety. J Parenter Enter Nutr 2013; 37(3): 617-22.
Mitchell K, Lyttle A, Amin H, Shaireen H, Robertson HL, Lodha AK. Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: An updated systematic review. BMC Pediatr 2014; 14: 226.
Ioannou HP, Diamanti E, Piretzi K. Plasma citrulline levels in preterm neonates with necrotizing enterocolitis. Early Hum Dev 2012; 88(7): 563-6.
Jiang P, Wan JM, Cilieborg MS, Sit WH, Sangild PT. Premature delivery reduces intestinal cytoskeleton, metabolism, and stress response proteins in newborn formula-fed pigs. J Pediatr Gastroenterol Nutr 2013; 56(6): 615-22.
Englund A, Rogvi RA, Melgaard L, Greisen G. Citrulline concentration in routinely collected neonatal dried blood spots cannot be used to predict necrotisingenterocolitis. Acta Paediatr 2014; 103(11): 1143-7.
Dilsiz A, Ciftçi I, Aktan TM, Gürbilek M, Karagözoğlu E. Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis. Pediatr Surg Int 2003; 19(8): 578-82.
Rhoads MJ, Wu G. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 2009; 37(1): 111-22.
Wang J, Chen L, Li P. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr 2008; 138(8): 1025-32.
Hackam DJ, Good M, Sodhi CP. Mechanisms of gut barrier failure in the pathogenesis of necrotizingenterocolitis: Toll-like receptors throw the switch. Semin Pediatr Surg 2013; 22(2): 76-82.
Zhou W, Li W, Zheng XH, Rong X, Huang LG. Glutamine downregulates TLR-2 and TLR-4 expression and protects intestinal tract in preterm neonatal rats with necrotizing enterocolitis. J Pediatr Surg 2014; 49(7): 1057-63.
Bober-Olesi’nska K, Kornacka MK. Effects of glutamine supplemented parenteral nutrition on the incidence of necrotizing enterocolitis, nosocomial sepsis and length of hospital stay in very low birth weight infants. Med WiekuRozwojowego 2005; 9(3 Pt1): 325-33.
Tubman TR, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2008; 23(1)CD001457
Sevastiadou S, Malamitsi-Puchner A, Costalos C, 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(10): 1294-300.
MohamadIkram I. Quah BS, Noraida R, Djokomuljanto S, FarisIrfan CY, Van Rostenberghe H. A randomised controlled trial of glutamine-enriched neonatal parenteral nutrition in Malaysia. Singap Med J 2011; 52(5): 356-60.
Pawlik D, Lauterbach R, Hurkała J, Radziszewska R. The effects of enteral administration of glutamine enriched solution in very low birth weight infants on reducing the symptoms of feeding intolerance, a prospective, randomized pilot study. MedWiekuRozwojowego 2012; 16(3): 205-11.
Kelley DS. Modulation of human immune and inflammatory responses by dietary fatty acids. Nutrition 2001; 17(7-8): 669-73.
Caplan MS, Russell T, Xiao Y, Amer M, Kaup S, Jilling T. Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model. Pediatr Res 2001; 49(5): 647-52.
Caplan MS, Jilling T. The role of polyunsaturated fatty acid supplementation in intestinal inflammation and neonatal necrotizing enterocolitis. Lipids 2001; 36(9): 1053-7.
Lee JY, Zhao L, Youn HS, et al. Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 2004; 279(17): 16971-9.
Ohtsuka Y, Okada K, Yamakawa Y, et al. Omega-3 fatty acids attenuate mucosal inflammation in premature rat pups. J Pediatr Surg 2011; 46(3): 489-95.
Martin CR, Dasilva DA, Cluette-Brown JE, et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr 2011; 159(5): 743-9.
Zhang P, Lavoie PM, Lacaze-Masmonteil T, Rhainds M, Marc I. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: A systematic review. Pediatrics 2014; 134(1): 120-34.
Barclay AR, Stenson B, Simpson JH, Weaver LT, Wilson DC. Probiotics for necrotizing enterocolitis: A systematic review. J Pediatr Gastroenterol Nutr 2007; 45(5): 569-76.
Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotizing enterocolitis in preterm neonates with very low birth weight: A systematic review of randomised controlled trials. Lancet 2007; 369(9537): 1614-20.
Alfaleh K, Anabrees J, Bassler D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: A meta-analysis. Neonatology 2010; 97(2): 93-9.
Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010; 125(5): 921-30.
Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of necrotizing enterocolitisandmortality in preterm very low-birth-weight infants: An updated meta-analysis of 20 randomized, controlled trials. J Pediatr Surg 2012; 47(1): 241-8.
Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2014; 10(4)CD005496
Chapman CM, Gibson GR, Rowland I. Health benefits of probiotics: Are mixtures more effective than single strains? Eur J Nutr 2011; 50(1): 1-17.
Carlisle EM, Morowitz MJ. The intestinal microbiome and necrotizing enterocolitis. Curr Opin Pediatr 2013; 25(3): 382-7.
Shiou SR, Yu Y, Guo Y, et al. Synergistic protection of combined probiotic conditioned media against neonatal necrotizing enterocolitis-like intestinal injury. PLoS One 2013; 8(5)e65108
Kunz AN, Fairchok MP, Noel JM. Lactobacillus sepsis associated with probiotic therapy. Pediatrics 2005; 116(2): 517-8.
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.
Bron PA, Kleerebezem M, Brummer RJ, et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr 2017; 117(1): 93-107.
Underwood MA. Impact of probiotics on necrotizing enterocolitis. Semin Perinatol 2017; 41(1): 41-51.
Munoz P, Bouza E, Cuenca-Estrella M, et al. Saccharomycescerevisiaefungemia: An emerging infectious disease. Clin Infect Dis 2005; 40(11): 1625-34.
Marchand V. Canadian Paediatric Society NaGC. Using probioticsin the paediatric population. Paediatr Child Health 2012; 17(10): 575.
Thomas DW, Greer FR. American Academy of Pediatrics Committeeon Nutrition. American Academy of Pediatrics Section on Gastroenterology, Hepatology, and Nutrition Probiotics and prebiotics inpediatrics. Pediatrics 2010; 126(6): 1217-31.
Ouwehand AC, Derrien M, de Vos W, Tiihonen K, Rautonen N. Prebiotics and other microbial substrates for gut functionality. Curr Opin Biotechnol 2005; 16(2): 212-7.
Butel MJ, Suau A, Campeotto F, et al. Conditions of bifido bacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastroenterol Nutr 2007; 44(5): 577-82.
Catala I, Butel MJ, Bensaada M, et al. Oligofructose contributes to the protective role of bifidobacteria in experimental necrotisingenterocolitis in quails. J Med Microbiol 1999; 48(1): 89-94.
Srinivasjois R, Rao S, Patole S. Prebiotic supplementation of formula in preterm neonates: Updated systematic review and meta-analysis of randomised controlled trials. Clin Nutr 2013; 32(6): 958-65.
Dilli D, Aydin B, Fettah ND. The ProPre-Save Study: Effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. J Pediatr 2015; 166(3): 545-51.
Armanian AM, Sadeghnia A, Hoseinzadeh M. The effect of neutral oligosaccharides on reducing the incidence of necrotizing enterocolitis in preterm infants: A randomized clinical trial. Int J Prev Med 2014; 5(11): 1387-95.
Tsukahara T, Iwasaki Y, Nakayama K, Ushida K. Stimulation of butyrate production in the large intestine of weaning piglets by dietary fructooligosaccharides and its influence on the histological variables of the large intestinal mucosa. J Nutr Sci Vitaminol (Tokyo) 2003; 49(6): 414-21.
Bartholome AL, Albin DM, Baker DH, Holst JJ, Tappenden KA. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets. JPEN J Parenter Enteral Nutr 2004; 28(4): 210-22.
Kanauchi O, Andoh A, Iwanaga T, et al. Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor kappa B activity in a spontaneous colitis model. J Gastroenterol Hepatol 1999; 14(12): 1173-9.
Yin L, Laevsky G, Giardina C. Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity. J Biol Chem 2001; 276(48): 44641-6.
Venkatraman A, Ramakrishna BS, Shaji RV, Kumar NS, Pulimood A, Patra S. Amelioration of dextran sulfate colitis by butyrate: Role of heat shock protein 70 and NFkappaB. Am J Physiol Gastrointest Liver Physiol 2003; 285(1): G177-84.
Avivi-Green C, Polak-Charcon S, Madar Z, Schwartz B. Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition. Oncol Res 2000; 12(2): 83-95.
Mentschel J, Claus R. Increased butyrate formation in the pig colon by feeding raw potato starch leads to a reduction of colonocyte apoptosis and a shift to the stem cell compartment. Metabolism 2003; 52(11): 1400-5.
Scheppach W, Weiler F. The butyrate story: Old wine in new bottles? Curr Opin Clin Nutr Metab Care 2004; 7(5): 563-7.
Manzoni P, Rinaldi M, Cattani S, et al. Bovinelactoferrin supplementation for prevention of late-onset sepsis in very low birth weight neonates: A randomized trial. JAMA 2009; 302(13): 1421e8.
Manzoni P, Meyer M, Stolfi I, et al. Bovinelactoferrin supplementation for prevention of necrotizing enterocolitis in very-low- birth weight neonates: A randomized clinical trial. Early Hum Dev 2014; 90(Suppl. 1): S60-5.
Pammi M, Suresh G. Enterallactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2017; 6CD007137
Terrin G. BerniCanani R, Di Chiara M, et al. Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate. Nutrients 2015; 7(12): 10427-46.
Terrin G, Berni Canani R, Passariello A, et al. Zinc supplementation reduces morbidity and mortality in very- low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country. Am J Clin Nutr 2013; 98(6): 1468-74.
Connolly JM, Rose DP. Epidermal growth factor-like proteins in breast fluid and human milk. Life Sci 1988; 42(18): 1751-6.
Hofmann GE, Abramowicz JS. Epidermal growth factor (EGF) concentrations in amniotic fluid and maternal urine during pregnancy. Acta Obstet Gynecol Scand 1990; 69(3): 217-21.
Harris RC, Chung E, Coffey RJ. EGF receptor ligands. Exp Cell Res 2003; 284(1): 2-13.
Jones MK, Tomikawa M, Mohajer B, Tarnawski AS. Gastrointestinal mucosal regeneration: Role of growth factors. Front Biosci 1999; 4: D303-9.
Yagi H, Suzuki S, Noji T, Nagashima K, Kuroume T. Epidermal growth factor in cow’s milk and milk formulas. Acta Paediatr Scand 1986; 75(2): 233-5.
Shin CE, Falcone RA Jr, Stuart L, Erwin CR, Warner BW. Diminished epidermal growth factor levels in infants with necrotizing enterocolitis. J Pediatr Surg 2000; 35(2): 173-6.
Warner BB, Ryan AL, Seeger K, Leonard AC, Erwin CR, Warner BW. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr 2007; 150(4): 358-63.
Clark JA, Lane RH, Maclennan NK, et al. Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2005; 288(4): G755-62.
Clark JA, Doelle SM, Halpern MD, et al. Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol 2006; 291(5): G938-49.
Good M, Siggers RH, Sodhi CP, et al. Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium. Proc Natl Acad Sci USA 2012; 109(28): 11330-5.
Faintuch J, Aguilar PB, Nadalin W. Relevance of N-acetylcysteine in clinical practice: Fact, myth or consequence? Nutrition 1999; 15(2): 177-9.
Koivusalo A, Kauppinen H, Anttila A, et al. Intraluminal casein model of necrotizing enterocolitis for assessment of mucosal destruction, bacterial translocation, and the effects of allopurinol and N-acetylcysteine. Pediatr Surg Int 2002; 18(8): 712-7.
Ozdemir R, Yurttutan S, Sar FN, et al. Antioxidant effects of N-acetylcysteine in a neonatal rat model of necrotizing enterocolitis. J Pediatr Surg 2012; 47(9): 1652-7.
Tayman C, Tonbul A, Kosus A, et al. N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis. J Pediatr Surg 2012; 47(3): 540-50.
Hou Y, Wang L, Yi D, et al. N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling. Amino Acids 2013; 45(3): 513-22.
Soghier LM, Brion LP. Cysteine, cystine or N-acetylcysteine supplementation in parenterallyfed neonates. Cochrane Database Syst Rev 2006; (4): CD004869
Juul SE, Joyce AE, Zhao Y, Ledbetter DJ. Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates. Pediatr Res 1999; 46(3): 263-8.
Juul SE, Yachnis AT, Christensen RD. Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus. Early Hum Dev 1998; 52(3): 235-49.
McPherson RJ, Juul SE. High-dose erythropoietin inhibits apoptosis and stimulates proliferation in neonatal rat intestine. Growth Horm IGF Res 2007; 17(5): 424-30.
Wald MR, Borda ES, Sterin-Borda L. Mitogenic effect of erythropoietinon neonatal rat cardiomyocytes: Signal transduction pathways. J Cell Physiol 1996; 167(3): 461-8.
Ledbetter DJ, Juul SE. Erythropoietin and the incidence of necrotizing enterocolitis in infants with very low birth weight. J Pediatr Surg 2000; 35(2): 178-81.
Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990; 97(1): 11-25.
Smith LM, Qureshi N, Chao CR. Effects of single and multiple courses of antenatal glucocorticoids in preterm newborns less than 30 weeks’ gestation. J Matern Fetal Med 2000; 9(2): 131-5.
Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (96 hours) corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2003; 1CD001146
Halliday HL, Ehrenkranz RA, Doyle LW. Delayed (3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2003; 1CD001145
Halliday HL, Ehrenkranz RA, Doyle LW. Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2003; 1CD001144
Stark AR, Carlo WA, Tyson JE, et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 2001; 344(2): 95-101.
Egan EA, Nelson RM, Mantilla G, Eitzman DV. Additional experience with routine use of oral kanamycin prophylaxis for necrotizing enterocolitis in infants under 1,500 grams. J Pediatr 1977; 90(2): 331-2.
Siu YK, Ng PC, Fung SC, et al. Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotisingenterocolitis in preterm, very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1998; 79(2): F105-9.
Burgio GR, Lanzavecchia A, Plebani A, Jayakar S, Ugazio AG. Ontogeny of secretory immunity: levels of secretory IgA and natural antibodies in saliva. Pediatr Res 1980; 14(10): 1111-4.
Eibl MM, Wolf HM, Furnkranz H, Rosenkranz A. Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding. New Engl J Med 1988; 319(1): 1-7.
Foster J, Cole M. Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates. Cochrane Database Syst Rev 2004; 1CD001816
Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and or low-birth-weight infants. Cochrane Database Syst Rev 2004; 1CD000361
Hsueh W, Sun X, Rioja LN, Gonzalez-Crussi F. The role of thecomplement system in shock and tissue injury induced bytumour necrosis factor and endotoxin. Immunology 1990; 70(3): 309e14.
Halpern MD, Clark JA, Saunders TA, et al. Reduction of experimental necrotizingenterocolitis with anti-TNF-alpha. Am J Physiol Gastrointest Liver Physiol 2006; 290(4): G757e64.
Emami CN, Chokshi N, Wang J, et al. Role of interleukin-10 in the pathogenesis of necrotizingenterocolitis. Am J Surg 2012; 203(4): 428e35.
Travadi J, Patole S, Charles A, Dvorak B, Doherty D, Simmer K. Pentoxifylline reduces the incidence and severity of necrotizingenterocolitis in a neonatal rat model. Pediatr Res 2006; 60(2): 185e9.

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Year: 2019
Published on: 13 March, 2019
Page: [92 - 105]
Pages: 14
DOI: 10.2174/1573396315666190313164753

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