Guest blog: Donor human milk: Supporting babies’ health and development

The Hearts Milk Bank is the UK’s newest milk bank, providing donor human milk to hospitals in London, the southeast and East Anglia, and community-based clinicians for babies across the UK, as well as planning a wide-ranging new programme of studies into milk banking and human milk. In this guest blog, co-founder Dr Natalie Shenker discusses the evidence behind the value of donor human milk, highlighting its important role in supporting the health of babies unable to receive their mother’s own milk.

The components of donor milk

Beyond providing nutrition and calories, human milk contains scores of broad classes of biologically active components, with many thousands of distinct molecules and organisms. These work individually and in combination to protect the baby against infection and inflammation and contribute to immune maturation, organ development, and colonization by healthy bacteria. Human milk has evolved specifically to support the development of human brains, immune system and gut microbiome.

For babies who are unable to receive their mother’s own milk, donor human milk (DHM) can play an important role in protecting their health and supporting their development. Although DHM undergoes processing, (including freezing, thawing and heat treatment), which affects the ability of some of the human milk components to function, it still contains a wide array of biologically active components that are not in the alternative, infant formula. DHM processing also makes the milk effectively sterile and destroys potentially harmful viruses, but is designed to be a balance between ensuring safety and maximising the range and function of the components after pasteurisation. Ongoing research is continuing to improve milk bank processes with simple, cost-effective interventions, such as nutritional supplementation for donors and improved transport and storage protocols.

Although research is developing rapidly in this area, the most well described components found in DHM are outlined below, along with their impact on infant health. A full list of components is available in the review by Peila et al. published in 2016.

Free fatty acids

Humans are particularly good at extracting medium and long chain polyunsaturated fatty acids (PUFAs) from their diet, of which the most common types found in milk are omega 9 (oleic acid), omega 3 (DHA, linolenic acid, eicosapentaenoic acid, etc.) and omega 6 (arachindonic acid, linoleic acid, etc.) molecules. Human milk contains high levels of these fats, as well as an array of fatty acids at lower concentrations, including potentially 1000s of breakdown products from the main PUFA molecules. Fats are digested in the infant gut into triglycerides and free fatty acids, which at high concentrations have anti-microbial functions. Some are targeted to support brain development and nerve conduction speeds, while others play roles in immune cell and cardiovascular development. The majority of functions of these components are unknown.

Human milk oligosaccharides (HMOs)

HMOs, formerly termed Bifidus factor or glycans, are unique to human milk and much more complicated molecules than oligosaccharides found in other species, including cow milk. Their function and volume are unaffected by pasteurisation in DHM. There are scores of structurally different HMOs, made up of chains of the simplest sugar, monosaccharides, and each mother produces a unique signature of HMOs (Bode 2015). Many HMOs cannot be digested by humans, but instead act as prebiotics (food) for particular bacteria (Marx 2014).

These bacteria develop a normal infant gut microbiome, helping the baby to resist infection with harmful bacteria, reduce the risk of autoimmune disease, and support brain development (Williams et al. 2017; Moukarzel and Bode, 2017). Laboratory tests have shown that if donor milk is seeded with a tenth of the volume of maternal milk, then the maternal microbiome becomes fully established after just 4 hours (Cacho et al. 2017). HMOs can also trick bacteria and viruses into binding to them, instead of the gut wall, preventing them from infecting the baby. Some studies suggest that HMOs may provide essential nutrients to the developing brain in the first two years of life.

Lactoferrin

Lactoferrin acts as a sump or collector of iron. It therefore deprives harmful bacteria such as Escherichia coli of iron, which is essential for their metabolism and growth. Volumes of lactoferrin have been shown to be reduced by 35-90% by pasteurisation, but it remains functional. Modern pasteurisation techniques, which include rapid cooling, minimise the reduction observed. The observed reduction might result from individual lactoferrin molecules clumping together during heat treatment, rather than a true reduction in their number, and ongoing studies are investigating this.

Lysozyme

Lysozyme is able to break down the building blocks of the outer cell walls of some bacteria. Studies have shown a reduction in absolute concentration in pasteurised compared to raw milk of 15-80%. Again, the method of pasteurisation is key to its persistent presence in donor milk. No significant difference in the function of lysozyme has been found after pasteurisation.

The difference for babies

The components discussed above work together to provide a host of health benefits to babies. Much of the ongoing debate about the use of DHM focuses on whether it confers a reduction in the risk of the serious and often fatal disease, necrotising enterocolitis (NEC). However, a growing understanding of the complexity of DHM supported by recent scientific findings regarding the microbiome, epigenetic patterning and immune system support, lends biological plausibility to more wide-ranging benefits:

Reduced duration of hospital stay

DHM is generally better tolerated by babies than infant formula, as it is not foreign antigen (non-human protein), and it is easier for the preterm and full term infant to digest. Babies supplemented with DHM on average spend one day less in a neonatal intensive care unit, with significant cost savings as a result (Renfrew et al. 2009, PHE 2018, Rollins et al. 2016, Unicef UK 2012).

Supporting maternal breastfeeding

The appropriate introduction and use of DHM has been repeatedly shown to increase maternal breastfeeding rates on discharge. These rates were shown to increase on average by 10% across 22 units that introduced DHM in the US (Kantorowska et al. 2016) and by 35% in a single centre in India (Abhisavam et al. 2017). A study of multiple European centres concluded, “[in terms] of exclusive breastmilk feeding (BMF), being admitted to a hospital with BMF protocols and donor milk provision was positively associated with the infants’ likelihood of exclusive BMF at discharge.” (Wilson et al. 2018).

One senior neonatologist who led the establishment of their hospital’s milk bank observed an increase in maternal breastfeeding rates from 35% to 75% on discharge after the first two years of operation. Ten years later, maternal breastfeeding rates are between 85-95% at discharge from the neonatal unit (Kingdon, unpublished, personal communication).

Another London-based hospital with its own milk bank has started to provide DHM to late preterm infants up to 36⁺⁶ weeks in an effort to help support maternal breastfeeding and change the culture of the units that care for these babies.

Other hospitals in England are examining the use of DHM as a supplement for full-term babies on the postnatal unit after several complaints from parents about their babies being fed with infant formula against their wishes. Mothers tend to view DHM as a temporary bridge to establishing their own lactation, and infant formula as a permanent switch (Kair and Flaherman, 2017). There is therefore the pressing need to develop evidence for the use of DHM beyond the current rationing, to assess the potential for impact on maternal breastfeeding, and this will be our focus in the next few years.

Protection against necrotising enterocolitis (NEC), other complications of prematurity and mortality

Extremely premature infants who receive an exclusive human milk diet have a significantly lower incidence of NEC and mortality as well as a reduction in late onset sepsis, bronchopulmonary dysplasia and retinopathy of prematurity (Zhou et al. 2015; Nino et al. 2016; Villamor-Martinez 2018). A Cochrane review reported that the use of infant formula in premature babies significantly increases the risk of NEC (Quigley & McGuire, 2014). More recent randomised controlled trials (RCTs) of human milk feeding in premature infants and risk of NEC reported that an exclusive human diet provides protection against NEC in the order of 4-fold risk reduction (DoMINO study, 2017). This is supported by other RCTs including Corpeleijn et al. 2017, showing an increase from 40% to 47% of adverse events (NEC, sepsis, death) at 60 days in babies supplemented with infant formula compared to DHM). Preterm infants are particularly susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in a number of ways: lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability and altering the composition of bacterial flora (Maffei and Schanler, 2017).

Cardiac development

A cohort study from Oxford showed that preterm babies fed with an exclusive human milk diet had improved cardiac development in terms of stroke volume and ejection fraction (Lewandowski 2014).

Building the evidence-base

In summary, the data to support the use of DHM in extremely preterm infants extends beyond the single question of the impact on NEC. A large, multi-centre randomised controlled trial would be the optimal study method to solve the questions surrounding the use of DHM for NEC, and we would wholeheartedly support this study. However, we suggest that there is a larger picture at play here, involving the culture of neonatal units to support maternal breastfeeding, the efficacy of DHM to reduce time to discharge, and the cost-savings incurred to the NHS and individual families as a result through the support of breastfeeding. At the Hearts Milk Bank, within our first eight months of operation, we have initiated or helped to enable a wide-ranging programme of research that aims to answer many of these outstanding questions. We anticipate that by starting to build a solid evidence base, donor milk can be used appropriately, sensibly and scientifically as well as more equitably in the infants who would benefit most.

References

• Adhisivam B, Vishnu Bhat B, Banupriya N, Poorna R, Plakkal N, Palanivel C. Impact of human milk banking on neonatal mortality, necrotizing enterocolitis, and exclusive breastfeeding – experience from a tertiary care teaching hospital, south India. J Matern Fetal Neonatal Med. 2017 Nov 1:1-4.
• Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev. 2015 Nov;91(11):619-22.
• Cacho NT, Harrison NA, Parker LA, Padgett KA, Lemas DJ, Marcial GE, Li N, Carr LE, Neu J, Lorca GL. Personalization of the Microbiota of Donor Human Milk with Mother’s Own Milk. Front Microbiol. 2017 Aug 3;8:1470.
• Corpeleijn WE, de Waard M, Christmann V, van Goudoever JB, Jansen-van der Weide MC, Kooi EM, Koper JF, Kouwenhoven SM, Lafeber HN, Mank E, van Toledo L, Vermeulen MJ, van Vliet I, van Zoeren-Grobben D. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. JAMA Pediatr. 2016 Jul 1;170(7):654-61.
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