Effectiveness of Human Milk-Based Fortifiers for Preventing Necrotizing Enterocolitis in Preterm Infants: Case Not Proven

This chapter describes historic steps in feeding techniques and knowledge about the nutritional needs of premature infants. Devices to overcome weak sucking and swallowing were developed from 1851 to 1920: tube feeding by gavage, medicine droppers and pipettes, feeding bottles with air inlet, and beaked spoons for nasal feeding. Indwelling nasogastric tubes were in use from 1951. For alleged safety concerns, postnatal feeding was postponed until a week of starvation was reached in the 1950s and studies showed an association with neurological handicaps. The premature infant’s elevated need for energy, protein, and minerals has been known since 1919. However, nutritional practice lagged behind theoretical knowledge. Concentrated formula was developed in the 1940s, parenteral supplementation in the 1960s, and human milk fortifiers in the 1970s. In the 1990s, necrotizing enterocolitis was found to be more frequent in infants fed formula than in those fed human milk. Recently, probiotics were shown to reduce the risk of necrotizing enterocolitis. Compared to other aspects of neonatal medicine, there is little evidence on how to feed preterm infants.

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The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review

Nutrients ◽

10.3390/nu12103052 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3052

Author(s):

Lila S. Nolan ◽

Jamie M. Rimer ◽

Misty Good

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Mode Of Delivery ◽

Intestinal Barrier ◽

Vulnerable Population ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Intestinal Homeostasis

Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.

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Feeding the feeble: steps towards nourishing preterm infants

Journal of Perinatal Medicine ◽

10.1515/jpm-2014-0054 ◽

2015 ◽

Vol 43 (5) ◽

Cited By ~ 1

Author(s):

Michael Obladen

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Premature Infants ◽

Tube Feeding ◽

Theoretical Knowledge ◽

Air Inlet ◽

Nutritional Needs ◽

The 1960S ◽

Feeding Techniques

AbstractThis paper describes historic steps in feeding techniques and knowledge on the nutritional needs of premature infants. Devices to overcome weak sucking and swallowing were developed from 1851 to 1920, including tube feeding by gavage, medicine droppers and pipettes, feeding bottles with an air inlet, and beaked spoons for nasal feeding. Indwelling nastrogastric tubes were in use from 1951. For alleged safety concerns in the 1950s, postnatal feeding was postponed until a week of starvation was reached, and studies showed an association with neurological handicaps. The premature infant’s elevated need for energy, protein, and minerals has been established since 1919. However, these remained controversial, and nutritional practices continued to lag behind theoretical knowledge. Concentrated formula was developed in the 1940s, parenteral supplementation in the 1960s, and human milk fortifiers in the 1970s. In the 1990s, necrotizing enterocolitis was found to be more frequent in infants who were fed formula than in those who were fed human milk. Recently, probiotics were shown to reduce the risk of necrotizing enterocolitis. Nevertheless, compared with other aspects of neonatal medicine, there is still remarkably little evidence on how to feed preterm infants.

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Human Milk Oligosaccharides to Prevent Gut Dysfunction and Necrotizing Enterocolitis in Preterm Neonates

Nutrients ◽

10.3390/nu10101461 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1461 ◽

Cited By ~ 26

Author(s):

Stine Bering

Keyword(s):

Preterm Birth ◽

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Bacterial Colonization ◽

Health Benefits ◽

Preterm Neonates ◽

Human Milk Oligosaccharides ◽

High Concentration ◽

Milk Oligosaccharides

This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant HMOs that serve as prebiotics and immunomodulators. Gut immaturity in preterm infants leads to difficulties in tolerating enteral feeding and bacterial colonization and a high sensitivity to NEC, particularly when breast milk is insufficient. Due to the immaturity of the preterm infants, their response to HMOs could be different from that in term infants. The concentration of HMOs in human milk is highly variable and there is no evidence to support a specifically adapted high concentration in preterm milk. Further, the gut microbiota is not only different but also highly variable after preterm birth. Studies in pigs as models for preterm infants indicate that HMO supplementation to formula does not mature the gut or prevent NEC during the first weeks after preterm birth and the effects may depend on a certain stage of gut maturity. Supplemented HMOs may become more important for gut protection in the preterm infants when the gut has reached a more mature phase.

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Oxidative Stress and Necrotizing Enterocolitis: Pathogenetic Mechanisms, Opportunities for Intervention, and Role of Human Milk

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7397659 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 19

Author(s):

Arianna Aceti ◽

Isadora Beghetti ◽

Silvia Martini ◽

Giacomo Faldella ◽

Luigi Corvaglia

Keyword(s):

Oxidative Stress ◽

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Antioxidant Status ◽

Antioxidant Properties ◽

Nutritional Intervention ◽

Antioxidant Defenses ◽

Antioxidant Compounds

This review will examine the role of oxidative stress (OS) in the pathogenesis of necrotizing enterocolitis (NEC) and explore potential preventive and therapeutic antioxidant strategies. Preterm infants are particularly exposed to OS as a result of several perinatal stimuli and constitutive defective antioxidant defenses. For this reason, OS damage represents a contributing factor to several complications of prematurity, including necrotizing enterocolitis (NEC). Being NEC a multifactorial disease, OS may act as downstream component of the pathogenetic cascade. To counteract OS in preterm infants with NEC, several antioxidant strategies have been proposed and different antioxidant compounds have been experimented. It is well known that human milk (HM) is an important source of antioxidants. At the same time, the role of an exclusive HM diet is well recognized in the prevention of NEC. However, donor HM (DHM) processing may impair antioxidant properties. As DHM is becoming a common nutritional intervention for high risk PI, the antioxidant status of preterm and DHM and potential ways to preserve its antioxidant capacity may merit further investigation.

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PIH18 ANALYSIS OF NECROTIZING ENTEROCOLITIS COSTS AMONG EXTREMELY PRETERM INFANTS FED EXCLUSIVELY HUMAN-MILK BASED DIET VS. HUMAN-MILK FORTIFIED WITH BOVINE-MILK BASED SUPPLEMENTS

Value in Health ◽

10.1016/s1098-3015(10)72895-3 ◽

2010 ◽

Vol 13 (3) ◽

pp. A183-A184

Author(s):

V Ganapathy ◽

JW Hay ◽

J Kim

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Bovine Milk ◽

Extremely Preterm ◽

Extremely Preterm Infants

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Analysis of Disialyllacto-N-Tetraose (DSLNT) Content in Milk From Mothers of Preterm Infants

Journal of Human Lactation ◽

10.1177/0890334420904041 ◽

2020 ◽

Vol 36 (2) ◽

pp. 291-298 ◽

Cited By ~ 1

Author(s):

Denise Hassinger ◽

Dana M. Clausen ◽

Sarah Nitka ◽

Aimee Herdt ◽

Ian Griffin

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Intestinal Perforation ◽

Protective Effects ◽

Human Donor ◽

Donor Milk ◽

Mothers Of Preterm Infants ◽

High Risk Infants ◽

Spontaneous Intestinal Perforation

Background Human milk oligosaccharides (HMO) have been recognized for the protective effects they may elicit among high risk infants. One HMO, disialyllacto-N-tetraose (DSLNT), has been shown to reduce the risk for developing necrotizing enterocolitis in preterm infants. Research aims To measure DSLNT content in the human milk from mothers of preterm infants, and (1) assess variability; (2) establish correlations between maternal factors and/or an infant’s risk for developing necrotizing enterocolitis; and (3) determine the effect of pasteurization. Methods DSLNT was measured in 84 samples of preterm milk, in human donor milk, and in Holder and flash pasteurized samples. Preterm infant outcomes were assessed by medical record review. Results DSLNT content of mother’s own milk was highly variable and decreased significantly with increasing postnatal age. Four preterm infants (6.7%) developed necrotizing enterocolitis (Bell stage II or greater), 4 (6.7%) developed spontaneous intestinal perforation, and 1 developed both. DSLNT z-score was below the age-specific M within 8 (89%) of the 9 milk samples from mothers whose babies developed necrotizing enterocolitis ( p = 0.039), but the DSLNT content did not differ between infants with necrotizing enterocolitis, spontaneous intestinal perforation, or neither condition ( p > 0.1). DSLNT levels were significantly reduced in samples of donor milk compared to mothers’ own milk ( p = 0.0051). Pasteurization did not significantly reduce DSLNT content. Conclusions DSLNT content of human milk is variable and may be lower in milk from mothers whose infants developed necrotizing enterocolitis. DSLNT content is unaffected by flash or Holder pasteurization.

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