Human milk and necrotizing enterocolitis

https://doi.org/10.1053/j.sempedsurg.2017.11.007Get rights and content

Abstract

NEC is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Human milk feedings, both from the infant’s mother and donor human milk, have been associated with reductions in NEC in preterm infants. This article will review the protective factors in human milk, clinical studies of human milk and NEC, and practices to enhance human milk use in neonatal intensive care units.

Section snippets

Objectives

  • 1.

    To review the known and potential protective factors in human milk that may reduce NEC

  • 2.

    To review the data that support a protective benefit of mother’s own milk, pasteurized donor human milk, and an “all-human” diet

  • 3.

    To review evidence for practical implementation of human milk in the NICU

The known and potential protective factors in human milk that may reduce NEC

The intestinal tract of a preterm infant is particularly vulnerable to injury and inflammation due to factors related to immaturity (Table 1). Enteral nutrition is a key factor in the development of NEC as it rarely occurs in preterm infants before enteral feeds begin. Also, enteral feeds impact the risk of NEC with reduced NEC rates associated with HM feedings in contrast to formula feedings.11, 12 Human and animal studies have demonstrated that bovine-based formula increases intestinal

MOM

Multiple clinical studies have demonstrated a dose-dependent relationship between MOM feeding and significant reductions in NEC. The MOM dose received during the first 14 days demonstrated increased survival time free of NEC with each 10% increase in MOM (Figure 1).11 Over the first 14 days, exclusive HM feedings, MOM and/or DHM, for the first 7 days47 and exclusive MOM for the first 14 days of life12 have been associated with significantly reduced odds of developing NEC. Two other thresholds

Evidence for feasibility of increasing utilization of human milk in the NICU

Increasing utilization of human milk in the NICU presents an important challenge. Expanding on the beneficial effects of the Baby Friendly Hospital Initiative in encouraging mothers of healthy term infants to breastfeed more, many institutions have been able to begin incorporating similar basic steps in the NICU to encourage a stronger culture for the use of human milk, MOM, and DHM.61, 62, 63 Multiple guidelines and examples have been published describing best practices to implement HM in the

Summary

Human milk contains numerous bioactive components that reduce the incidence and severity of NEC. MOM feedings supported with HMF compared to preterm formula provides the optimal nutrition for preterm infants that are associated with the lowest risk for NEC. Substitution of formula with DHM has been associated with reduction in risk of NEC, but since DHM differs significantly from MOM the emphasis on maximizing MOM is the best practice. Human milk-based HMF may add further to this protection

References (82)

  • H. Demmelmair et al.

    Variation of metabolite and hormone contents in human milk

    Clin Perinatol

    (2017)
  • K. Fugate et al.

    Improving human milk and breastfeeding practices in the NICU

    J Obstet Gynecol Neonatal Nurs

    (2015)
  • P.P. Meier et al.

    Improving the use of human milk during and after the NICU stay

    Clin Perinatol

    (2010)
  • J.H. Kim et al.

    Challenges in the practice of human milk nutrition in the neonatal intensive care unit

    Early Hum Dev

    (2013)
  • A.N. Trembath et al.

    Quality initiatives related to moderately preterm, late preterm, and early term births

    Clin Perinatol

    (2013)
  • B. Lonnerdal

    Nutritional and physiologic significance of human milk proteins

    Am J Clin Nutr

    (2003)
  • B. Lonnerdal

    Bioactive proteins in human milk: health, nutrition, and implications for infant formulas

    J Pediatr

    (2016)
  • O. Ballard et al.

    Human milk composition: nutrients and bioactive factors

    Pediatr Clin North Am

    (2013)
  • J. Neu et al.

    Necrotizing enterocolitis

    N Engl J Med

    (2011)
  • R.M. Patel et al.

    Intestinal microbiota and its relationship with necrotizing enterocolitis

    Pediatr Res

    (2015)
  • P.V. Gordon et al.

    Can a national dataset generate a nomogram for necrotizing enterocolitis onset?

    J Perinatol

    (2014)
  • C. Battersby et al.

    The impact of a regional care bundle on maternal breast milk use in preterm infants: outcomes of the east of England quality improvement programme

    Arch Dis Child Fetal Neonatal Ed

    (2014)
  • J. Meinzen-Derr et al.

    Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death

    J Perinatol

    (2009)
  • T.J. Johnson et al.

    Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants

    Neonatology

    (2015)
  • H. Shoji et al.

    Suppressive effects of breast milk on oxidative DNA damage in very low birthweight infants

    Arch Dis Child Fetal Neonatal Ed

    (2004)
  • A. Penn

    Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis

    Pediatr Res

    (2012)
  • M.C. Collado et al.

    Longitudinal study of cytokine expression, lipid profile and neuronal growth factors in human breast milk from term and preterm deliveries

    Nutrients

    (2015)
  • B. Dvorak et al.

    Concentrations of epidermal growth factor and transforming growth factor-alpha in preterm milk

    Adv Exp Med Biol

    (2004)
  • M.O. Labeta et al.

    Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14

    J Exp Med

    (2000)
  • M.A. Underwood et al.

    Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota

    Pediatr Res

    (2015)
  • P. Zhou et al.

    The role of immunonutrients in the prevention of necrotizing enterocolitis in preterm very low birth weight infants

    Nutrients

    (2015)
  • P.V. Jeurink et al.

    Human milk: a source of more life than we imagine

    Benef Microbes

    (2013)
  • S. Agarwal et al.

    Immune markers in breast milk and fetal and maternal body fluids: a systematic review of perinatal concentrations

    J Hum Lact

    (2011)
  • P.A. Ronayne de Ferrer et al.

    Lactoferrin levels in term and preterm milk

    J Am Coll Nutr

    (2000)
  • D. Rai et al.

    Longitudinal changes in lactoferrin concentrations in human milk: a global systematic review

    Crit Rev Food Sci Nutr

    (2014)
  • H. Wakabayashi et al.

    Inhibitory effects of bovine lactoferrin and lactoferricin B on enterobacter sakazakii

    Biocontrol Sci

    (2008)
  • R.R. Arnold et al.

    Bactericidal activity of human lactoferrin: influence of physical conditions and metabolic state of the target microorganism

    Infect Immun

    (1981)
  • R.T. Ellison et al.

    Killing of gram-negative bacteria by lactoferrin and lysozyme

    J Clin Invest

    (1991)
  • H. Demmelmair et al.

    Benefits of lactoferrin, osteopontin and milk fat globule membranes for infants

    Nutrients

    (2017)
  • M. Pammi et al.

    Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants

    Cochrane Database Syst Rev

    (2017)
  • Autran CA, Kellman BP, Kim JH, et al. Human milk oligosaccharide composition predicts risk of necrotising enterocolitis...
  • Cited by (75)

    • Enteral Nutrition: The Intricacies of Human Milk from the Immune System to the Microbiome

      2022, Clinics in Perinatology
      Citation Excerpt :

      These Bifidobacteria ferment oligosaccharides, causing the pH in the intestine to decrease and become more acidic. This acidic environment is bacteriostatic to pathogenic bacteria.38,41 There have been nearly 200 HMOs identified, and research continues to elucidate their role in infant immune function.40,42

    • Ethical Considerations for Hospital-Based Infant Feeding Support

      2022, JOGNN - Journal of Obstetric, Gynecologic, and Neonatal Nursing
    View all citing articles on Scopus
    View full text