Prevention of necrotising enterocolitis (NEC)

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Authors

Manzoni P, Hogeveen M, Schwindt E, Tissières P, Borghesi A

© Foto Video Sessner GmbH

Target group

Very preterm infants (<32 weeks gestational age), preterm infants (<37 weeks), 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).

Rationale

Necrotising enterocolitis (NEC) is a devastating bowel disease affecting approximately 7% of very preterm infants. The incidence of NEC increases with decrease in gestational age (GA). 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)

Prematurity is the main risk factor for NEC, thus preventing prematurity remains the main action in preventing NEC. Additional prenatal factors associated with an increased risk of NEC include fetal growth retardation, intrauterine infection and inflammation, the use of the antibiotic amoxicillin-clavulanic acid during pregnancy, and the use of indomethacin for tocolysis, while protective interventions include antenatal corticosteroids and the judicious use of antibiotic treatment when indicated. (6) Neonatal risk factors include absent or limited exposure to human milk, either donor or maternal (7,8), exposure to inhibitors of gastric acidity (9,10), exposure to cow-milk derived proteins provided as fortifier (7), or as formula milk (8), and the prolonged use of antibiotics during the first days of life. (11) The role of several other variables, such as changes in the daily increase in the amount of enteral feeding or packed red blood cells transfusion, have been assessed but to date there is no solid evidence of a direct causative relationship with the onset of NEC. (12,13)

A limited number of strategies have proven effective in reducing the prevalence of the most severe stages of NEC (5), including human milk, with fresh maternal milk being more protective than donor’s (8), and human milk-based fortifiers more protective than bovine milk-based fortifiers. (14,15) Conversely, a beneficial effect of bovine Lactoferrin (16), and of different preparations of probiotics, detected in some clinical trials, has only low to moderate level of certainty, and is still matter of investigation. (17–20) It is likely that only multifaceted, comprehensive strategies will consistently lead to the prevention of NEC.

Benefits

Short-term benefits

Long-term benefits

Components of the standard

Component

Grading of evidence

Indicator of meeting the standard

For parents and family

  1. Parents are informed by healthcare professionals, prenatally and postnatally, about the benefits of human milk feeding.(8)

A (High quality)
B (High quality)

Patient information sheet1

  1. Where human milk-based fortification products are available, parents are informed by healthcare professionals about the benefits of human milk-based fortification over bovine milk-based fortification.

B (Moderate quality)

Patient Information Sheet1

  1. Mothers are instructed about how to early initiate expressing breast milk (see Nutrition). (23)

A (High quality)

Parent feedback

  1. Parents are instructed by healthcare professionals about the need for hand hygiene to reduce the risk of nosocomial infections (see Patient safety & hygiene practice).

B (Moderate quality)

Patient information sheet1, training documentation

For healthcare professionals

  1. A written 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

  1. Own mother’s milk is used where available, donor milk is substituted if necessary, and where available. (3,8)

A (High quality)

Clinical records, guideline

  1. Where human milk-based fortification products are available human milk-based fortifiers should be preferred over bovine milk-based fortifiers. (14,15)

B (Moderate quality)

Guideline

  1. Specific probiotic preparation (either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH 4) are used following ESPGHAN. (17,18,20,24)

B (Moderate quality)

Guideline

  1. Inhibitors of gastric acidity (H2-blockers, proton pump inhibitors, etc.) and unnecessary antibiotics are avoided. (9,10)

A (High quality)

Guideline

  1. Appropriate insertion and management of umbilical vein and artery catheters is ensured (see standard Vascular access). (24,25)

A (Moderate quality)

Guideline

  1. Education and training of all healthcare professionals for the rapid recognition of a developing NEC (early warning clinical signs) and the immediate initiation of the first diagnostic and treatment steps to avoid or reduce late sequelae is provided.

B (Low quality)

Guideline

For neonatal unit

  1. A unit guideline on the implementation of bundles of care designed to prevent NEC is available and regularly updated.

B (High quality)

Guideline

  1. Standardised feeding protocols are available and regularly updated. (26,27)

A (High quality)

Guideline

  1. Healthcare professionals in the NICU are regularly educated, trained and updated by specifically trained staff members (parental counsellors) on the role of human milk and breastfeeding in preventing NEC.

B (High quality)

Guideline

  1. Antibiotic stewardship to reduce unnecessary antibiotics is adopted in each neonatal unit (see Patient safety & hygiene practice).

B (High quality)

Guideline

  1. Prenatal and postnatal counselling to the parents and to breastfeeding mothers is provided (see standards Promotion of breastfeeding and Providing mother’s own milk (MOM) for preterm and ill term infants). (28–31)

B (High quality)

Audit report2, clinical record

  1. The proportion of very preterm infants who develop NEC is audited regularly.

B (High quality)

Audit report2

For health service

  1. A national guideline on the implementation of a bundle of care designed to prevent NEC is available and regularly updated.

B (High quality)

Guideline

  1. Human milk banks are available. (19)

A (High quality)

Audit report2

1The indicator ‘patient information sheet’ is an example for written, detailed information, in which digital solutions are included, such as web-based systems, apps, brochures, information leaflets, and booklets.

2The indicator ‘audit report’ can also be defined as a benchmarking report.

Where to go – further development of care

Further development

Grading of evidence

For parents and family

N/A

For healthcare professionals and neonatal unit

  • Confirm the beneficial effect of specific probiotic preparations, define the optimal probiotic to be used in the NICU and address all safety issues.

B (Low quality)

  • Assess the beneficial effect of human milk-based fortifiers over bovine milk-based fortifiers.

B (Low quality)

  • Assess the role of blood transfusions/chronic anaemia, the effects of withholding of feeding before/during/after blood transfusion, speed of transfusion, withholding a change of feeding amount and amount of fortification during blood transfusions.

B (Moderate quality)

For hospital

  • Ensure availability of own mother´s milk and donor milk for all preterm infants. (32)

A (High quality)

  • Create incentives for special professions such as breastfeeding counsellors and make them mandatory in NICUs.

B (High quality)

For health service

N/A

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

  • Provide donor milk supply. (see Nutrition)

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. Watson SN, McElroy SJ. Potential Prenatal Origins of Necrotizing Enterocolitis. Gastroenterol Clin North Am. 2021 Jun;50(2):431–44.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Cantey JB, Pyle AK, Wozniak PS, Hynan LS, Sánchez PJ. Early Antibiotic Exposure and Adverse Outcomes in Preterm, Very Low Birth Weight Infants. J Pediatr. 2018 Dec 1;203:62–7.
  12. 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.
  13. 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.
  14. Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawöger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010 Apr;156(4):562-567.e1.
  15. Corrigendum for O’Connor et al. Nutrient enrichment of human milk with human and bovine milk–based fortifiers for infants born weighing < 1250 g: a randomized clinical trial. Am J Clin Nutr 2018;108:108–16. Am J Clin Nutr. 2019 Aug 1;110(2):529.
  16. 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.
  17. Chang HY, Chen JH, Chang JH, Lin HC, Lin CY, Peng CC. 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.
  18. 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.
  19. 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.
  20. Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2020 Oct 15;10:CD005496.
  21. Yeh TC, Chang JH, Kao HA, Hsu CH, Hung HY, Peng CC. 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.
  22. 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;
  23. 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.
  24. van den Akker CHP, van Goudoever JB, Shamir R, Domellöf M, Embleton ND, Hojsak I, et al. Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2020 May;70(5):664–80.
  25. Van Rens R, Helder O, Tissières P, Mader S, Thiele N, Borghesi A. Vascular access [Internet]. EFCNI; 2018. Available from: https://newborn-health-standards.org/standards/standards-english/patient-safety-hygiene-practice/vascular-access/
  26. El-Dib M, Narang S, Lee E, Massaro AN, Aly H. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. J Perinatol. 2011 Mar;31(3):183–7.
  27. Jasani B, Patole S. Standardized feeding regimen for reducing necrotizing enterocolitis in preterm infants: an updated systematic review. J Perinatol Off J Calif Perinat Assoc. 2017;37(7):827–33.
  28. Spatz DL. Innovations in the provision of human milk and breastfeeding for infants requiring intensive care. J Obstet Gynecol Neonatal Nurs JOGNN. 2012 Feb;41(1):138–43.
  29. Fugate K, Hernandez I, Ashmeade T, Miladinovic B, Spatz DL. Improving Human Milk and Breastfeeding Practices in the NICU. J Obstet Gynecol Neonatal Nurs JOGNN. 2015 Jun;44(3):426–38; quiz E14-15.
  30. Frauenfelder O, Oude-Reimer M, Camba F, Ceccatelli, Hankes-Drielsma I, Jørgensen E, et al. Promotion of breastfeeding [Internet]. EFCNI; 2018. Available from: https://newborn-health-standards.org/standards/standards-english/care-procedures/promotion-of-breastfeeding/
  31. Jonat S, Koletzko B, Fewtrell M, Embleton N, van Goudoever J, Gruszfeld D, et al. Providing mother’s own milk (MOM) for preterm and ill term infants [Internet]. EFCNI; 2022. Available from: https://newborn-health-standards.org/standards/standards-english/nutrition/providing-mothers-own-milk-mom-for-preterm-and-ill-term-infants/
  32. 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: http://www.ncbi.nlm.nih.gov/books/NBK66142/

September 2022 / 2nd edition / previous edition reviewed by Saenz de Pipaon / next revision: 2025

Recommended citation

EFCNI, Manzoni P, Hogeveen M et al., European Standards of Care for Newborn Health: Prevention of necrotising enterocolitis (NEC). 2022.

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