Prolacta in the News
Sarah M Reyes, PhD, Scientific Liaison and Consultant, Human Milk & Clinical Research, Prolacta Bioscience
With mounting evidence that an Exclusive Human Milk Diet (EHMD) provides improved outcomes for premature infants in hospital neonatal intensive care units (NICUs), there has been increased interest in different human milk processing technologies used to provide safe sources of donor human milk. In fact, the American Academy of Paediatrics recommends the use of donor human milk for premature infants when mother’s own milk (MOM) is not in adequate supply.
A safe supply of donor human milk is particularly important for very low birth weight infants, who often require the addition of nutritional fortifiers to MOM to meet their high nutritional needs. Fortifiers are predominantly made from either cow milk or human milk. However, evidence indicates that preterm infants fed human milk–based fortifiers experienced several improved outcomes, including a reduced incidence of necrotising enterocolitis. Some of these improvements are likely related to the bioactive components found in human milk.
Why bioactivity of human milk matters?
Human milk naturally contains a wide variety of bioactive compounds that have been shown to improve infant survival, development, and health. Notably, lactoferrin and α-lactalbumin enhance mineral absorption. Lactoferrin, lysozyme, and immunoglobulins provide protection against both bacterial and viral pathogens. Cytokines, polymeric immunoglobulin receptors (PIGR), and osteopontin promote a healthy immune system. Finally, transforming growth factor (TGF) β21 and lactoferrin are important for the healthy development of the gastrointestinal system.
Other crucial components of human milk are growth factors, which may promote healthy development of the infant intestinal tract, vasculature, nervous system, and endocrine system. Examples of such growth factors include vascular endothelial growth factor (VEGF), TGF-β1, and TGF-β2.
Retaining donor milk bioactivity
Many factors must be considered when selecting appropriate technology for the processing of human milk intended for vulnerable infants. First and foremost is safety. Like blood and other human tissue, human milk has the potential to harbour harmful pathogens that were either present in the milk donor or that were introduced during collection, processing, distribution, storage, or reconstitution.
Elimination or neutralisation of harmful pathogens introduced during collection and processing can be achieved with technologies that employ heat and pressure. These include retort sterilisation, ultra-high-temperature (UHT) processing, and vat pasteurisation. In retort sterilisation, packaged milk is sterilised by being heated to 115°–145°C under high pressure. The milk is then distributed and stored in the same packaging it was in during the retort sterilisation process, eliminating the risk of introducing new pathogens before it reaches a patient. It is marketed as the safest form of milk processing because it neutralises pathogenic spores, but this added safety comes at the price of destroying bioactive milk proteins that are important for infant health and development.
UHT processing produces shelf-stable milk by heating it to 135°C for 2 to 5 seconds and then filling and sealing it in sterile packaging in preparation for distribution. Both retort sterilisation and UHT processing are typically combined with homogenisation, to prevent the fat from separating out of solution and to reduce the browning of milk that can make it less visually appealing. Vat pasteurisation, which is equivalent to Holder pasteurisation, involves heating milk in individual batches at lower temperatures for a longer period than for either UHT processing or retort sterilisation.
Vat pasteurisation preserves higher levels of milk proteins and other substances in their bioactive state. Researchers have demonstrated this in a recent study in which they compared the effect of thawing, homogenising, vat pasteurisation, retort sterilisation, and UHT processing on the structure of bioactive proteins in donor human milk. They found that freeze-thawing, freeze-thawing plus homogenisation, and vat pasteurisation all preserved immunoglobulins important for immune function, notably secretory immunoglobulin A (sIgA), IgA, IgG, and IgM. In contrast, almost all immunoglobulins were degraded with retort sterilisation and UHT processing. PIGR immunoreactivity was unaffected by freeze-thawing, freeze-thawing plus homogenisation, and vat pasteurisation, but detection was increased with both retort sterilisation and UHT processing. All processing methods increased α-lactalbumin immunoreactivity. This increase in PIGR detection and α-lactalbumin immunoreactivity could be an indicator that bioactive proteins are degrading and interacting with each other during thermal processing.
VEGF, TGF-β1, and TGF-β2 were fully preserved with vat pasteurisation. VEGF and TGF-β2 were decreased by 37 to 61 per cent with UHT processing and by 92 to 99 percent with retort sterilisation. Osteopontin, a protein that is important for healthy immune function, was not altered by UHT processing but was degraded by about 50 percent with vat pasteurisation and by about 70 percent with retort sterilisation. The immunoreactivity of lactoferrin was reduced by 35 percent with freeze-thawing plus homogenisation, by 65 percent with vat pasteurisation, and by 84 percent with UHT processing. Lysozyme survived all processing conditions.
Choosing the best tech
The findings of Liang et al indicate that donor milk bioactivity most closely resembles that of MOM after vat pasteurisation, compared with either retort sterilisation or UHT processing. These findings provide manufacturers with data to make informed decisions about which technology to employ when processing human milk. A primary consideration here should be providing the optimal nutrition to meet patients’ needs. Since vulnerable infants in the NICU, have been shown to benefit from bioactivity that is as close as possible to MOM while ensuring microbiological safety, vat pasteurisation is currently the leading processing technology, based on current data.
Notably, the majority of research to date on the use of an EHMD in preterm infants has been conducted using nutritional fortifiers which employ vat pasteurisation. It remains unclear whether human milk–based nutrition that has been processed using another method will provide the same outcomes.
Challenges in ensuring safety and bioactivity
Retort sterilisation and UHT processing, both popular in the dairy industry, have benefits related to convenience and cost efficiency that make them better suited for producing foods for a non-vulnerable population, such as healthy children and adults. UHT is a form of continuous processing, which allows for high-volume production and reduced processing times. High thermal processing results in products that remain sterile during distribution and storage, provided the packaging remains intact. The final product is shelf stable for long periods of time, eliminating the need for temperature control during distribution and storage.
With vat pasteurisation, human milk and human milk–derived products are sampled and tested at multiple points in time. Some products may also be reserved to be tested after packaging. The final product is not shelf stable, requiring careful temperature control at all stages of distribution and storage. These additional steps are necessary when manufacturing a product intended for vulnerable preterm infants who are dependent on a nutritional product most similar to MOM. Meticulous testing for pathogens can be paired with testing for metabolites from drugs and for adulterants to further ensure a safe product. Thus, vat pasteurisation paired with testing for pathogens, adulterants, and drug metabolites would ensure both safety and preserved bioactivity.
Ensuring that premature infants treated in hospital NICUs receive a safe source of nutrition that resembles MOM as closely as possible is an important challenge for manufacturers of human milk–based nutrition. Evidence to date indicates that vat pasteurisation results in better preservation of bioactive proteins than either UHT processing or retort sterilisation.