Call for authors - Systematic reviews on donor human milk banking processes

Background

In 2022, the “WHO recommendations for care of the preterm or low birth weight infant” reconfirmed the previous 2011 “Guidelines on the optimal feeding of low birthweight (LBW) infants in low-and middle-income countries,” recommending that LBW infants, including those with very LBW, who cannot be fed mother's own milk should be fed donor human milk. This recommendation was qualified as being relevant for settings where safe and affordable milk-banking facilities are available or can be set up, reflecting a concern that the costs of ensuring that donor human milk is free of HIV and other infections may be prohibitive in very resource-limited settings.

The 2018 WHO/UNICEF implementation guidance on the Baby-friendly Hospital Initiative similarly stated that “Infants who cannot be fed their mother’s own milk, or who need to be supplemented, especially low birth weight infants, including those with very low birth weight and other vulnerable infants, should be fed donor human milk.” The American Academy of Pediatrics, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition, and other national and global policy groups also call for use of donor human milk as the feeding of choice, if mother’s own milk is insufficient, unavailable or contraindicated.

There is growing interest in creating and sustaining human milk banks globally to fulfil the need for donor human milk. Human milk banks have now been established in over 60 countries globally, with a small but increasing number of milk banks operating in low-income and middle-income countries.

WHO and the University of Zurich co-sponsored an international expert meeting in 2019 to examine issues on the implementation, operation, and regulation of human milk banks. The meeting identified a need for global guidance on the quality and safety of human milk banking. Significant questions need to be addressed on selection and screening of potential donors, transportation, storage and handling of milk, processing procedures, pasteurization, and equitable distribution. The meeting emphasized that the use of donor human milk must be managed in the context of protecting, promoting, and improving use of mother’s own milk wherever possible.

The WHO Department of Nutrition and Food Safety is in the process of creating guidance on donor human milk banking. In 2022, WHO formed an Expert Group (EG) for this purpose and, in December of 2022, convened the first of several planned EG meetings to discuss key questions and review the evidence to inform the guidelines. A second EG was held in March 2023, where a set of priority questions for recommendations on human milk banking was developed. 

Scope

To inform the guidance on donor human milk banking, WHO will commission several systematic reviews to retrieve, synthesize and assess the available evidence for the following priority questions. The questions have been formulated influenced by traditional PICO format, with two key modifications. The concept of “population” (or subject) of interest has been broadened to refer to the object being studied, which could be either people or milk, since the purpose of milk banking is to produce a safe and quality milk. Second, the “comparison” is not made explicit a priori to include studies that examine degrees of implementation, comparisons across multiple options, or simply the absence of the intervention.

1. What is the impact of storage,* handling,** and treatment*** on nutritional qualityⁱ and safetyⁱⁱ of animal milk?
• Subject details: Animal milk includes: cow, other animals (non-human)
• Intervention/exposure details:
• * refrigeration, freezing, length of timing, containers used for storage
• ** freeze-thaw number of times and methods, exposure to light
• *** containers used during processing, treatment methods (HPP, UVC irradiation, HTST, HoP, heat treatment (time/temperature), or thermoultrasonic)
• Outcome details:
• i : quality is defined by: nutritional composition, bioactivity retention
• ii : safety is defined by: contamination- microbial load (count and type- pathogen); viral load
2. What is the impact of maternal characteristics,* expression practices/techniques,** storage practices,*** mixing*+ and pooling*++ methods, or treatment,+ on nutritional qualityⁱ and safetyⁱⁱ of human milk?
• Subject details: Human milk includes mother’s own milk and donor milk; note where intervention only includes donor milk
• Intervention/exposure details:
• * lactation stage, disease/health status, birth outcome, drug/medicine exposure, diet (restrictive diet, or diet quality index), lifestyle factors (smoking, drinking, factors related with increased risk of select communicable diseases such as multiple sexual partners)
• ** type of expression method (hand expression, expression with (electric or manual, multi or single-user) breast pump, alternative expression methods (e.g. drip milk collectors); hygiene practices with expression (hand washing, cleaning/sanitizing supplies, setting of expression)
• *** container (material, construction, and shape) used in collection, number of container transfers, temperature and time/duration (differentiated by storage location in or out of facility, commercial or non-commercial storage equipment), lighting exposure (type and time), maintenance/cleaning of equipment and containers, freeze/thaw method and number of cycles
• *+ manual mixing, automatic mixing (donor milk only)
• *++ pooling from multiple donors with a variety of selection criteria (early vs. late term, time of day of expression, etc.); (donor milk only)
• + method (HPP, UVC irradiation, HTST, HoP, heat treatment (time/temperature), or thermoultrasonic), container used during processing
• Outcome details:
• i : quality is defined by: nutritional composition, bioactivity retention
• ii : safety is defined by: contamination- microbial load (count and type- pathogen); viral load; drug presence; environmental toxins
3. What is the impact of donating milk on health,ⁱ lactation,ⁱⁱ or wellbeingⁱⁱⁱ outcomes among donors?
• Population detials: donors included lactating individuals donating their milk who may have health concerns
• Note : Authors should report findings broken down by available information on donor health concerns (such as suboptimal birth outcomes (which include preterm, bereavement, low birthweight, etc.); BMI outside the healthy limit, acute or chronic illness)
• Intervention/exposure details: donating milk
• Note: Authors should report findings broken down by time period post-birth
• Outcome details:
• i : health outcomes, including nutritional and psychosocial
• ii : lactation outcomes, including milk supply, pumped milk feeding, breastfeeding exclusivity, breastfeeding duration, mastitis
• iii : wellbeing includes prevention of harm
4. What is the impact of donating milk from a donor at various stages of lactation,* or with a suboptimal birth outcome,** on healthi and growthii outcomes (O) of the donor's infant (P)?
• Intervention/exposure details:
• * variety of time periods post-birth
• ** suboptimal birth outcomes include preterm, bereavement, low birthweight, etc.
• Outcome details:
• i : health outcomes, including morbidity, mortality, tolerance, adverse events/effects, infections, deficiencies in micronutrients (e.g., B12, VA, iron), developmental outcomes
• ii : growth outcomes
5. What is the impact of feeding expressed breastmilk using varying expression practices/techniques,** or with treated/pasteurized milk*** on healthⁱ and growthⁱⁱ outcomes of infants fed their own mothers milk?
• Intervention/exposure details:
• * disease/health status, birth outcome, drug/medicine exposure, diet (restrictive diet, or diet quality index), lifestyle factors (smoking, drinking, factors related with increased risk of select communicable diseases), BMI outside of healthy limits, acute or chronic illness [limited to evidence from systematic reviews]
• ** type of expression method (hand expression, expression with (electric or manual, multi or single-user) breast pump, alternative expression methods (other collection devices/methods, drip milk collectors); hygiene practices with expression (hand washing, cleaning/sanitizing supplies, setting of expression)
• *** any heat treatment before milk is fed to infant
• Outcome details:
• i : health outcomes, including morbidity, mortality, tolerance, adverse events/effects, infections, deficiencies in micronutrients (e.g., B12, VA, iron), developmental outcomes
• ii : growth outcomes
6. What is the impact of breastfeeding* on healthi and growthii outcomes among infants of mothers with health concerns? [limited to evidence from systematic reviews]
• Population details: health concerns include
• disease/health status, birth outcome, drug/medicine exposure, diet (restrictive diet, or diet quality index), lifestyle factors (smoking, drinking, factors related with increased risk of select communicable diseases), BMI outside of healthy limits, acute or chronic illness
• Intervention/exposure details:
• * feeding directly at the breast or feeding with expressed mother’s own milk
• Outcome details:
• i : health outcomes, including morbidity, mortality, tolerance, adverse events/effects, infections, deficiencies in micronutrients (e.g., B12, VA, iron), developmental outcomes
7. What is the impact of feeding milk from donors with varying lactation stages,* health concerns,** varying expression practices/techniques,*** or with various treatment+ or testing^ methods on healthⁱ and growthⁱⁱ outcomes of infants fed donor milk?
• Intervention/exposure details:
• * variety of time periods post-birth
• **disease/health status, birth outcome, drug/medicine exposure, diet (restrictive diet, or diet quality index), lifestyle factors (smoking, drinking, factors related with increased risk of select communicable diseases), BMI outside of healthy limit, acute or chronic illness
• *** type of expression method (hand expression, expression with (electric or manual, multi or single-user) breast pump, alternative expression methods (other collection devices/methods, drip milk collectors); hygiene practices with expression (hand washing, cleaning/sanitizing supplies, setting of expression);
• + type of treatment performed for safety (e.g., HPP, UVC irradiation, HTST, HoP, heat treatment (time/temperature), or thermoultrasonic)
• ^ differentiated by pre- or post-pasteurization testing prior to feeding
• Outcome details:
• i : health outcomes, including morbidity, mortality, tolerance, adverse events/effects, infections, deficiencies in micronutrients (e.g., B12, VA, iron), developmental outcomes
• ii : growth outcomes

Concept note and budget

Interested author(s)/teams are invited to submit a concept note (2-3 pages) by sending an email to WHO at nfs@who.int no later than 5 November 2023. The subject heading of the email should read as, “Reviews on donor human milk banking”. 

The concept note should include a proposal containing (preferably in a single pdf document) the following:

• The lead author and host institution with overall responsibility for the review, and contributors. The specific competencies and contributions of each author or team member should be explicitly stated.
• Proposed question(s) to be addressed through systematic reviews, outlining the background and justification for the review, the search strategy and databases to be searched, definition of inclusion/exclusion criteria, process of data extraction and analytical approach. This description should reflect the scope of work described below. Author(s)/teams may undertake one or more reviews. However, they need to demonstrate capacity to conduct the review(s) within the timeline below. Successful authors will be required to submit a protocol prior to performing the review;
• Budget (US $). This should outline the total amount for the review including an approximate breakdown of personnel vs. institutional/other costs. It is expected that WHO will provide technical input on the final protocols that will govern the systematic reviews. For the purpose of the concept note, it is not necessary to describe every detail of the systematic review.

Scope of work

• Conduct a systematic review or review of evidence to answer specified questions above. This will include the following activities:
• Create a systematic review protocol;
• Develop a search strategy in consultation with WHO and in collaboration with an information specialist/research librarian;
• Identify eligible studies for inclusion;
• Perform data synthesis (meta-analysis where appropriate);
• Produce evidence tables, as appropriate
• Produce a report that includes a completed PRISMA 2020 Checklist.
• Assess and report quality of evidence
• Create catalogue of included studies (full text), accessible to WHO.
• Systematic reviews should include the following:
• Detailed methods that align with the review protocol (and any protocol deviations)
• Table of included studies and characteristics;
• List of excluded studies (full-texts screened) with detailed reasons for exclusion
• Narrative summaries of the results of included studies covering all outcomes of interest
• Meta-analyses for each of the outcomes of interest for which there were data (if applicable)
• The following criteria should be used for systematic review:
• No date or language restrictions in search strategy
• Geographic areas: Disaggregate studies conducted in low- and middle-income countries from those in high income countries
• Outcome measures: those listed in the questions
• Outcome measures: those listed in the questions
• Work closely with the WHO Steering Committee to align the systematic review protocol and systematic review to be fit for purpose; Be responsive to feedback on deliverables, seeking WHO approval at each step of the review process (protocol and search strategy development, etc.) Attend meetings to answer questions from the Expert Group.

Qualifications of the author(s) / review team

• Interested author(s)/teams must have experience with conducting systematic reviews of evidence. Applicants should provide examples of previously published reviews. Additionally, author(s)/teams must have demonstrated capacity to deliver comparable projects per the time and on budget.
• Interested author(s)/teams should demonstrate knowledge of key aspects of the issues on the processes of donor human milk banking.
• Interested author(s)/teams should have: members with complementary skills and competencies in statistical analysis, excellent writing capabilities, and outstanding proficiency in written English.
• Interested author(s)/teams are recommended to work with an information specialist/research librarian. 

Timeline

• 5 November 2023 - Interested authors or teams submit concept notes and budget
• 21 November 2023 - WHO review of proposals complete and authors/teams contacted
• 15 December 2023 - Contracts agreed (subject to WHO conditions including review of declarations of interest of members of the systematic review teams)
• 9 February  2024- Systematic review protocols agreed upon with WHO
• 19 April 2024 - Draft systematic reviews submitted
• 17 May 2024 - Final systematic reviews with GRADE tables submitted