
==== Front
JPGN Rep
JPGN Rep
10.1002/(ISSN)2691-171X
JPR3
JPGN Reports
2691-171X
John Wiley and Sons Inc. Hoboken

39149198
10.1002/jpr3.12102
JPR312102
Original Article
Original Article
Nutrition
The impact of storage, handling, and treatment on nutritional quality and safety of animal milk: A protocol for the systematic review and meta‐analysis
ALWASILA et al.
Alwasila Roba 1
Berg Alaina http://orcid.org/0009-0008-4577-9253
2
Colaizy Tarah 3
Smith Abigail 4
Evans James 4
Hassan Murad Mohammad 5
Bhutta Zulfiqar Ahmed 6 7 8 9
Imdad Aamer http://orcid.org/0000-0002-7026-0006
10 aamer-imdad@uiowa.edu

1 College of Public Health The University of Iowa Iowa City Iowa USA
2 The University of Iowa Carver College of Medicine Iowa City Iowa USA
3 Division of Neonatology, Stead Family Department of Pediatrics University of Iowa Carver College of Medicine Iowa City Iowa USA
4 Health Sciences Library State University of New York Upstate Medical University Syracuse New York USA
5 Division of Preventive, Occupational and Aerospace Medicine, Department of Internal Medicine Mayo Clinic Rochester Minnesota USA
6 Centre for Global Child Health Hospital for Sick Children Toronto Ontario Canada
7 Centre of Excellence in Women and Child Health Aga Khan University Karachi Pakistan
8 Institute for Global Health and Development Aga Khan University Karachi Pakistan
9 Department of Nutrition Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto Toronto Ontario Canada
10 Division of Gastroenterology, Hepatology, Pancreatology, and Nutrition, Stead Family Department of Pediatrics University of Iowa Carver College of Medicine Iowa City Iowa USA
* Correspondence Aamer Imdad, Division of Gastroenterology, Hepatology, Pancreatology, and Nutrition, Stead Family Department of Pediatrics, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA.
Email: aamer-imdad@uiowa.edu

24 6 2024
8 2024
5 3 10.1002/jpr3.v5.3 342346
16 5 2024
16 4 2024
19 5 2024
© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Abstract

Objectives

Human milk has been shown to reduce severe morbidity in preterm/low‐birth‐weight infants and is therefore the recommended nutritional source. When infants cannot receive maternal milk, donor human milk (DHM) is recommended. The use of human milk banking facilities is increasing to meet the need for DHM. DHM is unique compared to maternal milk as it must be processed and stored. The processing and storage of animal milk has been more rigorously studied than human milk and can serve as proxy to create DHM banking guidelines.

Methods and Analysis

We will search electronic databases, grey literature, and the websites of relevant international organizations. We will include studies that evaluated the impact of storage, handling, and treatment on the nutritional quality and safety of animal milk. We will not restrict study date, language, or design. If sufficient homogeneity exists between studies, we will conduct a meta‐analysis. We will evaluate the methodological quality of each study using the SYRCLE's (Systematic Review Centre for Laboratory Animal Experimentation) risk of bias tool. (1) We will evaluate the overall certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Conclusion

In this systematic review and meta‐analysis, commissioned by the World Health Organization, we will synthesize the available literature regarding the impact of various storage, handling, and treatment practices on the nutritional quality and safety of animal milk.

What is Known

• Breastmilk is the recommended nutritional source for infants, and the use of donor human milk (DHM) is increasing worldwide.

• The impact of processing and storage of animal milk on its nutritional quality and safety can help understand how processing and storage practices for DHM could affect nutritional quality and safety.

• There has been no systematic review published to date regarding the effect of storage, handling, and treatment practices on the nutritional quality and safety of animal milk.

What is New

• In this World Health Organization‐commissioned systematic review and meta‐analysis, we will summarize and synthesize the available literature regarding the impact of storage, handling, and treatment practices on the nutritional quality and safety of animal milk.

cow's milk
dairy milk
pasturization
WHO (Performance of Work (APW))2024/1445457 source-schema-version-number2.0
cover-dateAugust 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:25.09.2024
Alwasila R , Berg A , Colaizy T , et al. The impact of storage, handling, and treatment on nutritional quality and safety of animal milk: a protocol for the systematic review and meta‐analysis. JPGN Rep. 2024;5 :342‐346. 10.1002/jpr3.12102 39149198
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pmc1 INTRODUCTION

Globally, around 13 million babies are born prematurely (before 37 weeks of pregnancy), 1 and over 20 million with low birth weight (less than 2.5 kg), each year. 2 The American Academy of Pediatrics, World Health Organization, and European Society of Pediatric Gastroenterology, Hepatology, and Nutrition recommend the use of maternal breast milk for feeding preterm and low‐birth‐weight infants and support the use of donor human milk (DHM) for feeding preterm infants when maternal milk is not available. 3 , 4 , 5

Concerns have been raised about DHM's nutritional adequacy, as it has been associated with poorer growth outcomes in preterm infants compared with those fed with preterm formula or maternal milk. 3 , 6 , 7 This discrepancy has highlighted a need for comprehensive research due to various factors involved in the process of DHM storage, handling, and treatment which may alter its nutrient content. 8 The process of pasteurization and storage has been shown to decrease some bioactive factors and nutrients. 9

There is limited experience with the collection, processing, and storage of DHM. 8 The processing and storage of animal milk has been more rigorously studied and can serve as a proxy for understanding the processing and storage of human milk.

In this World Health Organization (WHO)‐commissioned systematic review and meta‐analysis, we aim to synthesize and evaluate the available literature regarding the impact of the methods of storage, handling, and treatment practices on the nutritional quality and safety of animal milk.

2 METHODS

This systematic review is being commissioned by the WHO, conducted following the standard guidelines of Cochrane Collaboration, and reported following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. 10 This systematic review will be completed in consultation with the WHO. The protocol was registered with the Open Science Framework (Registration ID: https://doi.org/10.17605/OSF.IO/BHPXZ)

3 ELIGIBILITY CRITERIA

3.1 Type of population

The population of interest encompasses milk derived from animal milk including cow's milk, buffalo milk, goat milk, camel milk, and donkey's milk. We will exclude the studies on synthetic milk, condensed animal milk, dried milk, or other dairy products such as yogurt or cheese.

3.2 Type of intervention and comparator

The exposure of interest is the storage, handling, and treatment of animal milk. The storage methods include refrigeration, freezing, length of timing of storage, and containers used for storage. Methods for handling include the following: freeze‐thaw number of times and methods, and exposure to light. The methods of treatment include methods for prevention of contamination such as high‐pressure pasteurization, ultraviolet C irradiation, high‐temperature/short time, Holder pasteurization, heat treatment (time/temperature), or thermoultrasonic methods. 11 , 12

We will consider a comparison group without the procedure of interest for storage, handling, and treatment. However, we will not exclude a study because of the lack of a control group.

3.3 Types of studies

While randomized controlled trials (RCTs) are typically preferred for assessing interventions, it is anticipated that RCTs might be limited or unavailable in the context of our research on storage, handling, and treatment of animal milk. Consequently, our review will adopt a more inclusive approach, encompassing a range of study designs. We will include observational studies and quasi‐experimental studies with a control group. We will exclude case studies and opinion pieces.

3.4 Types of outcomes measures

To be included in the systematic review, studies must report at least one of the following outcomes: 1. Primary outcomes: Nutritional quality: This includes assessing changes in essential nutrients like proteins, fats, vitamins, and minerals in animal milk. a. Macronutrient: Quantity of protein (g/dL) (continuous).

b. Macronutrient: Quantity of carbohydrate (g/dL) (continuous).

c. Macronutrient: Quantity of fat (g/dL); Fat oxidation (continuous).

d. Micronutrient: Quantity of vitamins such as vitamins A, D, and B12 (µg/mL) (continuous).

e. Micronutrients: Quantity of minerals such as iron, zinc, phosphorus, potassium, sodium, magnesium, and calcium (g/kg) (continuous).

f. Immunoglobulins: Quantity of immunoglobulin (Ig) A, IgG, and IgM (g/L) (continuous).

g. Lipase: Quantity of lipase in milk (lipoprotein lipase, etc.): (g/L) (continuous).

2. Secondary outcomes: Safety: We will evaluate the safety of animal milk, focusing on the presence of contaminants, pathogens, or any other factors that could pose health risks, influenced by various handling, storage, and treatment practices. a. Presence of contaminants (dichotomous).

b. Presence of pathogens (dichotomous).

c. Presence of alkaline phosphatase (dichotomous): this is a heat‐labile enzyme that serves as a marker of unsuccessful pasteurization as it is completely wiped out with pasteurization.

3.5 Information sources

Electronic searches will be conducted across multiple databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, CINHAL, Scopus, and the WHO Global Index Medicus. We will impose no limitations on the searches in terms of outcomes, study design, publication status, date, or language. Our proposed search strategy for PubMed is detailed in File S1.

3.6 Other sources

We will explore ClinicalTrials.gov for any ongoing or unpublished studies. The search will extend to websites of relevant international organizations like WHO, United Nations Children's Fund (UNICEF), the Global Alliance for Improved Nutrition, and the International Food Policy Research Institute. This includes veterinary‐focused databases such as Centre for Agriculture and Biosciences International (CAB) Abstracts and VetMed Resource to cover aspects of veterinary medicine relevant to our study, and milk bank associations like the Human Milk Bank Association of North America and the European Milk Bank Association. We will also meticulously review the reference lists of previously published reviews and recent studies to identify any further eligible studies.

4 STUDY RECORDS

4.1 Study selection process

All studies identified in the electronic search will be exported to Covidence for screening. 13 Two authors will independently screen all titles and abstracts to identify studies relevant to the research question. Then, those studies identified as relevant will be screened with a full‐text review to determine if they are eligible for inclusion. A third author will be available to resolve any conflicts during screening. We will include a list of studies that were excluded after full‐text screening and provide detailed reasons for their exclusion.

4.2 Data collection and management process

Studies deemed eligible for inclusion during the full‐text review step will then proceed with full data extraction. Two authors will independently extract data for each study, and any conflicts will be resolved by discussion with the help of the senior author on the team as needed. The following information with be extracted for each study: first author, publication date, study site, study year, study population, intervention, comparison, outcomes, and risk of bias. The methodological quality of each study will be assessed using the SYRCLE's (Systematic Review Centre for Laboratory Animal Experimentation) risk of bias tool. 14 We will contact the authors if data for exposure or outcomes is missing from reports. For continuous outcomes, if a study does not report a standard deviation (SD) for a mean and this cannot be calculated from the reported data and information is unavailable from authors, we will use an SD reported from a similar study for the same outcome.

4.3 Data synthesis

We will report a table of the characteristics of the included studies, and a separate table for the summary of findings for the primary outcomes. We will also report narrative summaries of the results of included studies regarding the outcomes of interest. Studies from low‐ and middle‐income countries will be reported separately from those from high‐income countries. We will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to evaluate the overall certainty of the evidence, using the GradePro software. 15 We will report the results of the GRADE assessment in the table which summarizes the findings for primary outcomes, with each finding characterized as very low, low, moderate, or high certainty.

We will conduct and report meta‐analyses when data is available from more than one study and there is sufficient clinical and methodological homogeneity between studies. Meta‐analyses will report dichotomous outcomes with relative risk and corresponding 95% confidence intervals. We will report continuous outcomes with mean effect size estimates and corresponding 95% confidence intervals. We will calculate the statistical heterogeneity of effect sizes using the χ 2 and I 2 statistics. Funnel plots and regression tests for funnel plot asymmetry will be used to assess small studies and publication bias if/when the meta‐analysis includes 10 or more studies. We will use the statistical software RevMan and Stata to complete the analyses. 16 , 17

5 SUBGROUP ANALYSES

1. Storage conditions: temperature, duration.

2. Handling practices: transportation methods and hygiene standards.

3. Treatment techniques: various treatment methods (e.g., pasteurization, homogenization).

4. Time: time between milking and processing on milk quality and safety.

6 SENSITIVITY ANALYSIS

1. Meta‐analysis with fixed effect model.

7 ETHICS

This systematic review and meta‐analysis would not directly involve human subjects and was considered a non‐human subject research by Institutional Reviw Board of University of Iowa (IRB no 202406271).

8 DISSEMINATION

The findings will be published in a peer‐reviewed journal and intended to inform the WHO recommendations for human milk banking.

9 CONCLUSION

This systematic review and meta‐analysis will synthesize the available literature regarding the effect of storage, handling, and treatment of animal milk on its nutritional quality and safety. This information will be useful to guide the WHO's development of global standards for the storage, handling, and treatment of DHM in human milk banks.

CONFLICT OF INTEREST STATEMENT

Dr. Colaizy is the research director of the research committee of the Human Milk Banking Association of North America (HMBANA). She contributes to this position on a volunteer basis and has never received any honorarium from HMBANA. This proposal was not discussed in the research committee of HMBANA, and HMBANA did not have any role in the design of this study. The remaining authors declare no conflict of interest.

Supporting information

Supplementary information.

ACKNOWLEDGMENTS

This systematic review is funded by WHO (Performance of Work (APW) Reference No. 2024/1445457).
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