Prevention of necrotising enterocolitis (NEC)


Manzoni P, Tissières P, Helder O, Borghesi A

Target group

Very preterm infants and parents

User group

Healthcare professionals, neonatal units, hospitals, and health services

Statement of standard

Neonatal services implement bundles of care designed to prevent necrotising enterocolitis (NEC).


Necrotising enterocolitis (NEC) is a devastating bowel disease affecting approximately 7% of very preterm infants. It is associated with increased mortality, serious neonatal morbidity, prolonged NICU stay, high costs, late neurodevelopmental impairment, and decreased quality of life in survivors. (1–5)

The pathogenesis of NEC is multifactorial, including gut immaturity, infection, enteric colonisation by pathogens, and local vascular injury, in the presence of milk. (1–4) Risk factors include absence or limited exposure to human milk, either donor or maternal (6,7), exposure to inhibitors of gastric acidity (8,9), and exposure to cow-milk derived proteins provided as fortifier (6), or as formula milk (7). Changes in the daily increase in the amount of enteral feeding or packed red blood cells transfusion have not been directly related to the onset of NEC. (10,11)

A limited number of strategies have proven effective in reducing the prevalence of the most severe stages of NEC (5), including human milk (7), and potentially probiotics (12–14) and bovine Lactoferrin (15). It is likely that only multifaceted, comprehensive strategies will consistently lead to the prevention of NEC.


Short-term benefits

  • Reduced risk of NEC and comorbidity (6,7,13)
  • Reduced mortality (16)

Long-term benefits

  • Reduced risk of poor neurodevelopmental outcome (16,17)
  • Reduced risk of poor nutritional outcome including impaired growth and dependence on nutritional devices (consensus)
  • Reduced healthcare costs (consensus)

Components of the standard

Component Grading of evidence Indicator of meeting the standard
For parents and family    
1. Parents are informed by healthcare professionals about the benefits of human milk feeding. (7) A (High quality)
B (High quality)
Patient information sheet
2. Mothers are instructed about how to early initiate expressing breast milk. (18) (see TEG Nutrition) A (High quality) Parent feedback
3. Parents are instructed by healthcare professionals about the need for hand hygiene to reduce the risk of nosocomial infections. (see TEG Patient safety & hygiene practice) B (Moderate quality) Patient information sheet, training documentation
For healthcare professionals    
4. A unit guideline on the implementation of bundles of care designed to prevent necrotising enterocolitis (NEC) is adhered to by all healthcare professionals. B (High quality) Guideline
5. Own mother´s milk is used where available, donor milk is substituted if necessary. (3,7) A (High quality) Clinical records, guideline
6. Probiotics are recommended. (12,13) A (High quality) Guideline
7. Inhibitors of gastric acidity (H2-blockers, proton pump inhibitors, etc.) are avoided. (8,9) A (High quality) Guideline
For neonatal unit    
8. A unit guideline on the implementation of bundles of care designed to prevent NEC is available and regularly updated. B (High quality) Guideline
9. The proportion of very preterm infants who develop NEC is audited. B (High quality) Audit report
For health service    
10. A national guideline on the implementation of bundles of care designed to prevent NEC is available and regularly updated. B (High quality) Guideline
11. Human milk banks are available. (19) A (High quality) Audit report

Where to go

Further development Grading of evidence
For parents and family  
For healthcare professionals and neonatal unit  
  • Define the optimal probiotic to be used in the NICU.
B (Low quality)
For hospital  
  • Ensure availability of own mother´s milk and donor milk. (19)
A (High quality)
For health service  

Getting started

Initial steps
For parents and family
  • Parents are verbally instructed by healthcare professionals about the importance of the use of own mother´s milk where available and in the benefits of donor milk as a substitute.
For healthcare professionals
  • Monitor the proportion of very preterm infants who develop necrotising enterocolitis (NEC).
For neonatal unit
  • Develop and implement a unit guideline on bundles for prevention practices for NEC.
  • Develop information material about the benefits of human milk feeding and the need for hand hygiene for parents.
For hospital
For health service
  • Develop and implement a national guideline on the implementation of bundles of care designed to prevent NEC.
  1. Manzoni P, Meyer M, Stolfi I, Rinaldi M, Cattani S, Pugni L, et al. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum Dev. 2014 Mar;90:S60–5.
  2. Sherman MP, Bennett SH, Hwang FFY, Yu C. Neonatal small bowel epithelia: enhancing anti-bacterial defense with lactoferrin and Lactobacillus GG. Biometals Int J Role Met Ions Biol Biochem Med. 2004 Jun;17(3):285–9.
  3. Adamkin DH. Mother’s milk, feeding strategies, and lactoferrin to prevent necrotizing enterocolitis. JPEN J Parenter Enteral Nutr. 2012 Jan;36(1 Suppl):25S-9S.
  4. Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010 May;125(5):921–30.
  5. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978 Jan;187(1):1–7.
  6. Abrams SA, Schanler RJ, Lee ML, Rechtman DJ. Greater mortality and morbidity in extremely preterm infants fed a diet containing cow milk protein products. Breastfeed Med Off J Acad Breastfeed Med. 2014 Aug;9(6):281–5.
  7. Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013 Dec;163(6):1592-1595.e1.
  8. More K, Athalye-Jape G, Rao S, Patole S. Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very low-birth-weight infants. Am J Perinatol. 2013 Nov;30(10):849–56.
  9. Manzoni P, García Sánchez R, Meyer M, Stolfi I, Pugni L, Messner H, et al. Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect. J Pediatr. 2018 Feb;193:62-67.e1.
  10. Hay S, Zupancic JAF, Flannery DD, Kirpalani H, Dukhovny D. Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature. Semin Perinatol. 2017;41(1):80–91.
  11. Karagol BS, Zenciroglu A, Okumus N, Polin RA. Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. JPEN J Parenter Enteral Nutr. 2013 Mar;37(2):223–8.
  12. Chang H-Y, Chen J-H, Chang J-H, Lin H-C, Lin C-Y, Peng C-C. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis. PloS One. 2017;12(2):e0171579.
  13. Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD005496.
  14. Pammi M, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2015 Feb 20;(2):CD007137.
  15. Corpeleijn WE, Kouwenhoven SMP, Paap MC, van Vliet I, Scheerder I, Muizer Y, et al. Intake of own mother’s milk during the first days of life is associated with decreased morbidity and mortality in very low birth weight infants during the first 60 days of life. Neonatology. 2012;102(4):276–81.
  16. Yeh T-C, Chang J-H, Kao H-A, Hsu C-H, Hung H-Y, Peng C-C. Necrotizing enterocolitis in infants: clinical outcome and influence on growth and neurodevelopment. J Formos Med Assoc Taiwan Yi Zhi. 2004 Oct;103(10):761–6.
  17. Allendorf A, Dewitz R, Weber J, Bakthiar S, Schloesser R, Rolle U. Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants – match control study after 2years. J Pediatr Surg. 2018 Jan 31;
  18. Meier PP, Johnson TJ, Patel AL, Rossman B. Evidence-Based Methods That Promote Human Milk Feeding of Preterm Infants: An Expert Review. Clin Perinatol. 2017 Mar;44(1):1–22.
  19. Centre for Clinical Practice at NICE (UK). Donor Breast Milk Banks: The Operation of Donor Milk Bank Services [Internet]. London: National Institute for Health and Clinical Excellence (UK); 2010 [cited 2018 May 4]. (National Institute for Health and Clinical Excellence: Guidance). Available from:

November 2018 / 1st edition / next revision: 2021 Recommended citation

EFCNI, Manzoni P, Tissières P et al., European Standards of Care for Newborn Health: Prevention of necrotising enterocolitis (NEC). 2018.

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