Clinical Impact of Supplementation with Pasteurized Donor Human Milk by High-Temperature Short-Time Method versus Holder Method in Extremely Low Birth Weight Infants: A Multicentre Randomized Controlled Trial.

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis.

High-Temperature Short-Time and Holder Pasteurization of Donor Milk: Impact on Milk Composition.

Holder pasteurization (HoP; 62.5 °C, 30 min) is commonly used to ensure the microbiological safety of donor human milk (DHM) but diminishes its nutritional properties. A high-temperature short-time (HTST) system was designed as an alternative for human milk banks. The objective of this study was to evaluate the effect of this HTST system on different nutrients and the bile salt stimulated lipase (BSSL) activity of DHM. DHM was processed in the HTST system and by standard HoP. Macronutrients were measured with a mid-infrared analyzer. Lactose, glucose, myo-inositol, vitamins and lipids were assayed using chromatographic techniques. BSSL activity was determined using a kit. The duration of HTST treatment had a greater influence on the nutrient composition of DHM than did the tested temperature. The lactose concentration and the percentage of phospholipids and PUFAs were higher in HTST-treated than in raw DHM, while the fat concentration and the percentage of monoacylglycerides and SFAs were lower. Other nutrients did not change after HTST processing. The retained BSSL activity was higher after short HTST treatment than that following HoP. Overall, HTST treatment resulted in better preservation of the nutritional quality of DHM than HoP because relevant thermosensitive components (phospholipids, PUFAs, and BSSL) were less affected.

Inactivation Kinetics of Coxiella burnetii During High-Temperature Short-Time Pasteurization of Milk.

The Gram-negative, obligate intracellular bacterium Coxiella burnetii is the causative organism of the zoonosis Q fever and is known for its resistance toward various intra- and extracellular stressors. Infected ruminants such as cattle, sheep, and goats can shed the pathogen in their milk. Pasteurization of raw milk was introduced for the inactivation of C. burnetii and other milk-borne pathogens. Legal regulations for the pasteurization of milk are mostly based on recommendations of the Codex Alimentarius. As described there, C. burnetii is considered as the most heat-resistant non-spore-forming bacterial pathogen in milk and has to be reduced by at least 5 log10-steps during the pasteurization process. However, the corresponding inactivation data for C. burnetii originate from experiments performed more than 60 years ago. Recent scientific findings and the technological progress of modern pasteurization equipment indicate that C. burnetii is potentially more effectively inactivated during pasteurization than demanded in the Codex Alimentarius. In the present study, ultra-high heat-treated milk was inoculated with different C. burnetii field isolates and subsequently heat-treated in a pilot-plant pasteurizer. Kinetic inactivation data in terms of D- and z-values were determined and used for the calculation of heat-dependent log reduction. With regard to the mandatory 5 log10-step reduction of the pathogen, the efficacy of the established heat treatment regime was confirmed, and, in addition, a reduction of the pasteurization temperature seems feasible.

Effect of HTST and Holder Pasteurization on the Concentration of Immunoglobulins, Growth Factors, and Hormones in Donor Human Milk.

Donor human milk (DHM) is submitted to Holder pasteurization (HoP) to ensure its microbiological safety in human milk banks but this treatment affects some of its bioactive compounds. The objective of this work was to compare the effects of HoP and high temperature short time (HTST) treatments on some bioactive compounds found in DHM. A total of 24 DHM batches were processed in a continuous HTST system (70, 72, and 75°C for 5-25 s) and by HoP (62.5°C for 30 min). The concentrations of immunoglobulins (Igs) A, G, and M, transforming growth factor-beta 2 (TGF-ß2), adiponectine, ghrelin, and leptin were measured using a multiplex system, whereas the concentration of epidermal growth factor (EGF) was determined by ELISA. In relation to Igs, IgG showed the highest preservation rates (87-101%) after HTST treatments, followed by IgA (54-88%) and IgM (25-73%). Ig retention after any of the HTST treatments was higher than after HoP (p < 0.001). Treatment times required to reduce the concentration of IgM by 90% (D-value) were 130, 88, and 49 s at 70, 72, and 75°C, while the number of degrees Celsius required to change the D-value by one factor of 10 (z-value) was 11.79°C. None of the heat treatments had a significant effect on the concentrations of TGF-ß2, EGF, adiponectin, and ghrelin. In contrast, leptin was detected only in 4 of the samples submitted to HoP, whereas it was present in all samples after the different HTST treatments, with retention rates ranging between 34 and 68%. Globally, the concentration of IgA, IgG, IgM, and leptin in DHM was significantly higher after HTST pasteurization performed in a continuous system designed to be used in human milk banks than after the HoP procedure that is routinely applied at present.

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting.

Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min). Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST) pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination) processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L). In conclusion, processing of donor milk at 72°C for at least 10 s in this HTST system allows to achieve the microbiological safety objectives established in the milk bank while having a lower impact regarding the heat damage of the milk.