Benefit by design: Determining the 'value' of donor human milk and medical products derived from human milk in NICU.

The use of donor human milk to provide therapeutic benefit to infants should only proceed where there is positive 'value'. This can be determined through an assessment of the benefit and the known risks. The emergence of new products derived from human milk requires new value assessments. The known hazards in human milk are modified by differences in the donor selection, processing methods and intended use and result in a unique risk assessment where any of these factors vary. The human source of the raw product requires high ethical standards in the design of these services with care taken to protect donors and recipients from harm. Any supplement to maternal milk should be provided cautiously to avoid displacement of maternal lactation.

A clinical audit of the growth of preterm infants fed predominantly pasteurised donor human milk v. those fed mother's own milk in the neonatal intensive care unit.

Preterm infants whose mothers are unable to produce sufficient breast milk are increasingly being supplemented with pasteurised donor human milk (PDHM) instead of commercial preterm infant formula. Concerns have been raised that this practice can result in reduced growth. This retrospective clinical audit collected data from the medical records of a cohort of preterm infants (≤30 weeks gestational age) receiving either ≥28 d of PDHM (n 53) or ≥28 d of their mother's own milk (MOM, n 43) with standard fortification supplied to both groups during admission. Weight growth velocity was assessed from regained birth weight to 34+1 weeks' postmenstrual age (PMA); and weight, length and head circumference were compared at discharge and 12 months (corrected age). At 34+1 weeks' PMA, the weight growth velocity (g/kg per d) was significantly lower in the PDHM group (15·4 g/kg per d, 95 % CI 14·6, 16·1) compared with the MOM group (16·9 g/kg per d, 95 % CI 16·1, 17·7, P=0·007). However, the increase was still within clinically acceptable limits (>15 g/kg per d) and no significant difference was observed in the weight between the two groups. There was no significant difference in weight between the groups at discharge or at the 12-month corrected gestational age review. Although we demonstrated a significant reduction in the weight growth velocity of preterm infants receiving PDHM at 34 weeks' PMA, this difference is not present at discharge, suggesting that the growth deficit is reduced by supplementation before discharge.

Ensuring Safety in Donor Human Milk Banking in Neonatal Intensive Care.

The provision of donor human milk avoids the risks associated with early infant formula feeding only when maternal milk is unavailable. Donor human milk-banking services (DHMBS) should provide an effective clinical service that causes no harm to donors or recipients. This article aims to begin the process of defining the minimum acceptable standard required for safe donor human milk banking in the neonatal unit. An assessment process is established to consider the potential risks and benefits of milk banking to both recipients and donors. These risks and benefits define the clinical responsibility of DHMBS and their social responsibility.

Breast milk donation after neonatal death in Australia: a report.

Lactation and breast milk can hold great value and meaning for grieving mothers who have experienced a recent death of an infant. Donation to a human milk bank (HMB) as an alternative to discarding breast milk is one means of respecting the value of breast milk. There is little research, national policy discussion, or organizational representation in Australia on the subject of breast milk donation after infant death. On 29 November 2013 the Mercy Hospital for Women in Melbourne, Australia hosted Australia's first National Stakeholder Meeting (NSM) on the topic of milk donation after neonatal death. The NSM drew together representatives from Australian HMBs, neonatal intensive care units (NICUs) currently using donor human milk, and Australia's chief NICU parent support organization. The NSM was video-recorded and transcribed, and analyzed thematically by researchers. This article reports the seven dominant themes discussed by stakeholders during the NSM: the spectrum of women's lactation and donation experiences after infant death; the roles of the HMB and NICU in meeting the needs of the bereaved donor; how bereaved mothers' lactation autonomy may interface with a HMB's donation guidelines; how milk donation may be discussed with bereaved mothers; the variation between four categories of milk donation after neonatal death; the impact of limited resources and few HMBs on providing donation programs for bereaved mothers in Australia. This article provides evidence from researchers and practitioners that can assist HMB staff in refining their bank's policy on milk donation after infant death, and provides national policy makers with key considerations to support lactation, human milk banking, and bereavement services nation-wide.

The effect of UV-C pasteurization on bacteriostatic properties and immunological proteins of donor human milk.

BACKGROUND: Human milk possesses bacteriostatic properties, largely due to the presence of immunological proteins. Heat treatments such as Holder pasteurization reduce the concentration of immunological proteins in human milk and consequently increase the bacterial growth rate. This study investigated the bacterial growth rate and the immunological protein concentration of ultraviolet (UV-C) irradiated, Holder pasteurized and untreated human milk. METHODS: Samples (n=10) of untreated, Holder pasteurized and UV-C irradiated human milk were inoculated with E. coli and S. aureus and the growth rate over 2 hours incubation time at 37°C was observed. Additionally, the concentration of sIgA, lactoferrin and lysozyme of untreated and treated human milk was analyzed. RESULTS: The bacterial growth rate of untreated and UV-C irradiated human milk was not significantly different. The bacterial growth rate of Holder pasteurized human milk was double compared to untreated human milk (p<0.001). The retention of sIgA, lactoferrin and lysozyme after UV-C irradiation was 89%, 87%, and 75% respectively, which were higher than Holder treated with 49%, 9%, and 41% respectively. CONCLUSION: UV-C irradiation of human milk preserves significantly higher levels of immunological proteins than Holder pasteurization, resulting in bacteriostatic properties similar to those of untreated human milk.

Ultraviolet-C Irradiation: A Novel Pasteurization Method for Donor Human Milk.

BACKGROUND: Holder pasteurization (milk held at 62.5°C for 30 minutes) is the standard treatment method for donor human milk. Although this method of pasteurization is able to inactivate most bacteria, it also inactivates important bioactive components. Therefore, the objective of this study was to investigate ultraviolet irradiation as an alternative treatment method for donor human milk. METHODS: Human milk samples were inoculated with five species of bacteria and then UV-C irradiated. Untreated and treated samples were analysed for bacterial content, bile salt stimulated lipase (BSSL) activity, alkaline phosphatase (ALP) activity, and fatty acid profile. RESULTS: All five species of bacteria reacted similarly to UV-C irradiation, with higher dosages being required with increasing concentrations of total solids in the human milk sample. The decimal reduction dosage was 289±17 and 945±164 J/l for total solids of 107 and 146 g/l, respectively. No significant changes in the fatty acid profile, BSSL activity or ALP activity were observed up to the dosage required for a 5-log10 reduction of the five species of bacteria. CONCLUSION: UV-C irradiation is capable of reducing vegetative bacteria in human milk to the requirements of milk bank guidelines with no loss of BSSL and ALP activity and no change of FA.

Longitudinal analysis of protein glycosylation and ß-casein phosphorylation in term and preterm human milk during the first 2 months of lactation.

Human milk proteins provide term and preterm infants with both nutrition and protection. The objective of the present study was to examine longitudinal changes in the protein composition of term and preterm milk during the first 2 months of lactation, focusing on protein phosphorylation and glycosylation. Using gel electrophoresis, the relative concentration and glycosylation status of lactoferrin, secretory Ig A, ß-casein, α-lactalbumin, serum albumin, bile salt-stimulated lipase, xanthine oxidoreductase, tenascin and macrophage mannose receptor 1 were measured in milk collected on days 7, 10, 14, 18, 21, 28 and 60 postpartum from preterm mothers (28-32 weeks gestation, n 17). The phosphorylation status of ß-casein was also investigated. To determine if these variables differ in term and preterm milk, samples from term mothers (38-41 weeks gestation, n 8) collected on days 7, 14 and 30 of lactation were also analysed. The concentration of the abundant milk proteins decreased during lactation in term and preterm milk (P <0·05). No difference in protein glycosylation was observed, except for the glycoproteins serum albumin and tenascin. The phosphorylation of ß-casein varied significantly between term and preterm milk. Further investigation is required to determine whether these modifications affect protein function and are clinically important to preterm infants.

Donor human milk banking and the emergence of milk sharing.

Donor human milk has emerged as the preferred substrate to feed extremely preterm infants, when mother's own milk is unavailable. This article summarizes the clinical data demonstrating the safety, efficacy, and cost-effectiveness of feeding donor human milk to premature babies. It describes the current state of milk banking in North America, as well as other parts of the world, and the differing criteria for donor selection, current pasteurization techniques, and quality control measures. A risk assessment methodology is proposed, which would allow milk banks globally to assess the safety of their process and respond appropriately to differing risk environments.

Proteome mapping of human skim milk proteins in term and preterm milk.

The abundant proteins in human milk have been well characterized and are known to provide nutritional, protective, and developmental advantages to both term and preterm infants. However, relatively little is known about the expression of the low abundance proteins that are present in human milk because of the technical difficulties associated with their detection. We used a combination of electrophoretic techniques, ProteoMiner treatment, and two-dimensional liquid chromatography to examine the proteome of human skim milk expressed between 7 and 28 days postpartum by healthy term mothers and identified 415 in a pooled milk sample. Of these, 261 were found in human skim milk for the first time, greatly expanding our understanding of the human skim milk proteome. The majority of the proteins identified were involved in either the immune response (24%) or in cellular (28%) or protein (16%) metabolism. We also used iTRAQ analysis to examine the effects of premature delivery on milk protein composition. Differences in protein expression between pooled milk from mothers delivering at term (38-41 weeks gestation) and preterm (28-32 weeks gestation) were investigated, with 55 proteins found to be differentially expressed with at least 90% confidence. Twenty-eight proteins were present at higher levels in preterm milk, and 27 were present at higher levels in term milk.

The knowns and unknowns of human milk banking.

The PREM Bank has been providing pasteurised donor human milk (PDHM) to very preterm for the past 3 years. It is the first human milk bank (HMB) to operate in Australia in over 20 years. Our community has rapidly embraced the concept of human milk banking, with both donations and demand for PDHM exceeding expectations. Providing PDHM in 'exceptional circumstances' where a mothers' own milk is unavailable is supported by the WHO and UNICEF. We submit that neonatal intensive care is an exceptional circumstance. Although evidence supporting PDHM use from randomised control trial (RCT) is limited, the latest systematic reviews suggest a lower risk of necrotising enterocolitis with PDHM as opposed to artificial formula. Study design and ethical issues may limit future evidence from RCT. We therefore support the ongoing use of PDHM in neonatal care, where provided by an appropriately managed HMB. Internationally many HMBs operate unregulated, and this is also the case in Australia. To ensure safety the PREM Bank has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) in Australia and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually re-evaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. HMB networks will facilitate collection of evidence for refining HMB practice and improving outcomes for preterm and sick infants.

Retention of the immunological proteins of pasteurized human milk in relation to pasteurizer design and practice.

Pasteurizing donor human milk inactivates bacteria that may be of concern to the preterm infant. However, current practice for Holder Pasteurization (62.5 degrees C for 30 min) is detrimental to the bioactivity of human milk. An experimental pasteurizer was used to determine the maximum temperature at which 90% of secretory IgA, lysozyme, and lactoferrin were retained and whether this temperature was capable of inactivating five common bacterial contaminants. The retention of these proteins was also compared using a commercially available bottle immersion or holding chamber system. After pasteurization at 62.5 degrees C for 30 min, the retention across all three systems was 72.3 +/- 3.6%, 21.8 +/- 3.3%, and 39.4 +/- 11.5% for sIgA, lactoferrin, and lysozyme, respectively (n = 22). The retention of all three proteins was at least 90% when human milk was pasteurized at 57 degrees C for 30 min, and this temperature was also effective at removing 99.9% of all inoculated bacterial species. In addition, human milk that was pasteurized in the experimental system had a significantly higher proportion of lysozyme compared with samples pasteurized in the bottle immersion system. These findings suggest that optimizing pasteurization temperature and improving pasteurizer design enhances the quality of pasteurized donor human milk.