Efficacy of Human Milk Concentration Device: A Nutrient...

July 19, 2019 MMIB_Protocol_v1

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Efficacy of Human Milk Concentration Device: A Nutrient Analysis of Mother’s Milk Pre and Post Concentration

Table of Contents

Abstract ............................................................................................................................................................. 2

Specific Aim 1 ..................................................................................................................................................... 2

Objective ....................................................................................................................................................... 3

Specific Aim 2 ..................................................................................................................................................... 3

Objectives ..................................................................................................................................................... 3

Background ....................................................................................................................................................... 4

Study Procedures ............................................................................................................................................... 5

Specific Aim 1 ................................................................................................................................................ 5

Specific Aim 2 ................................................................................................................................................ 9

Study Duration ............................................................................................................................................. 10

Inclusion/Exclusion Criteria ............................................................................................................................... 10

Specific Aim 1 ............................................................................................................................................... 10

Specific Aim 2 ............................................................................................................................................... 10

Drugs/Substances/Devices ................................................................................................................................ 11

Study Statistics .................................................................................................................................................. 11

Specific Aim 1 ............................................................................................................................................... 11

Specific Aim 2 ............................................................................................................................................... 13

Early stopping rules. .......................................................................................................................................... 13

Specific Aim 1 ............................................................................................................................................... 13

Specific Aim 2 ............................................................................................................................................... 13

Confidentiality and Privacy of Subjects .............................................................................................................. 13

Specific Aim 1 ............................................................................................................................................... 13

Specific Aim 2 ............................................................................................................................................... 14

Risks ................................................................................................................................................................. 14

Specific Aim 1 ............................................................................................................................................... 14

Specific Aim 2 ............................................................................................................................................... 15

Plan for reporting unanticipated problems or study deviations. .................................................................... 15

Legal risks such as the risks that would be associated with breach of confidentiality. .................................... 15

Financial risks to the participants. ................................................................................................................. 15

Benefits ............................................................................................................................................................ 15

Payment and Remuneration .............................................................................................................................. 16

Specific Aim 1 ............................................................................................................................................... 16

Specific Aim 2 ............................................................................................................................................... 16

Costs ................................................................................................................................................................. 16

References ........................................................................................................................................................ 17


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Abstract

Human milk is the best feeding option for preterm infants. However, due to the high nutrient needs of preterm infants in US Neonatal Intensive Care Units (NICUs), the mother’s own milk is most often mixed with bovine milk sourced fortifiers to achieve goal nutrient levels. The Human Milk Concentration (HMC) device concentrates a mother’s milk by removing water so that preterm infants can receive adequate nutrients from their own mother’s milk and not rely on the current fortifiers which can cause feeding intolerance. This device allows caregivers the option to feed preterm infants the valuable nutrients only found in mother’s milk, increasing their chance of survival. The goal of this specific aim 1 is to understand the technical capabilities of this device, the first product to fortify milk without the loss of key bioactives and nutrients not found in fortifiers. We will study these key nutrients by quantifying the levels of concentration when the HMC device is used to concentrate raw mother’s milk. It will also be confirmed that no nutrient was destroyed or denatured during the process. Given our initial benchtop studies, we believe that this study will demonstrate that the HMC will concentrate mother’s milk. The goal of specific aim 2 is to understand the clinical requirements required for adoption so that this device can be commercialized as the first product to fortify milk without the loss of key bioactives and nutrients not found in fortifiers. In this specific aim, MMIB will be conducting qualitative and quantitative research to create evidence base for practical adoption of HMC device use in NICUs. Based on a comprehensive voice of customer, the clinical workflow and requirements for the device will be created. The user protocol will be optimized to create consistency in the nutrient density of concentrated mother’s own milk, reduce risk of contamination, and prevent inadvertent misuse.

Specific Aim 1

Study Type: Non-Interventional Study Design Endpoint Classification: Efficacy Study Masking: Open Label Primary Purpose: Basic Science Official Title: Trial testing the efficacy of concentration human milk using the human milk concentration device

Endpoint Intervention

Concentration of nutrients using the human milk n/a


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concentration device

Objective

Primary 1. Determine the concentration levels of various nutrients (living stem cells, enzymes,

oligosaccharides, lipids, bioactives) using the HMC device

Secondary 1. Rate of concentration using Human Milk Concentration Device (volume reduction

given incubation time) 2. Understand milk management in the NICU setting

Specific Aim 2 Study Type: Non-Interventional Study Design Endpoint Classification: Efficacy Study Intervention Model: Crossover Design Masking: Open Label Primary Purpose: Human Factors and Qualitative Research Official Title: Trial testing the efficacy of concentration human milk using the human milk concentration device

Endpoint Intervention

• Instructions for use of HMC device

• Initial Human factors

• Marketing Requirement Document

• Risk Management Document

none

Objectives

Primary 3. Observe milk management practices and identify potential risks and benefits of the

for HMC device implementation in the clinical environment 4. Understand how the HMC device could be integrated into the workflow with

minimal disruption 5. Learn about the different practices of milk management within facilities 6. Determine the required concentration volume and form factor of the device 7. Develop a risk management document based on safety concerns determined by the

research collected


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Table 1 Sample Size (n) and Average %

Concentration Change for Raw Milk

Concentrated by HMC under refrigeration

Figure 1 Representative Graph of Pasteurized and

Raw Milk Concentration for Warmed, Room

Temperature, Refrigerated of Milk Volume over Time

Secondary 1. Help bring awareness to best practices in milk management

2. Aide in the global initiative to increase breastfeeding by identifying potential areas for improvement

Background Mother’s own milk provides immense benefits to mother and child, especially for preterm infants. In this fragile population, it is imperative that they receive as many of the benefits of mother’s own milk including bioactives, stem cells, enzymes, and mactronutirents, to develop immune function, growth and organ development [1-4]. When the mother’s own milk does not have the nutrient concentration necessary (given the volume of milk), fortification methods are used to increase the caloric density. While necessary to provide an infant with nutrients, these fortification methods can cause feeding complications including gut inflammation, sepsis and necrotizing enterocolitis [5-9]. These feeding complications can

lead to large hospital bills, longer hospitals stays and in some cases infant death. The Human Milk Concentration Device, when placed in mother’s milk, extracts water from the milk reducing its volume thus increasing its nutrient concentration. The Human Milk Concentration Device uses a passive membrane technology so the nutrients will not be exposed to extreme temperatures, agitation

or other filtering techniques that can damage the integrity of the nutrients. With regard to specific aim 1, preliminary data has shown that the HMC removes the water from both pasteurized and raw milk over time in situations where the milk has been kept in the refrigerator, room temperature or warmed (Figure 1). Initial nutrient concentrations have also been quantified (Table 1) including leptin, protein, fat, insulin, Immunoglobulin A (IgA), IgG, IgM, epidermal growth factors, non-protein nitrogen (NPN), Lactose, and tryptophan (trp). The proposed research will create the further evidence that the HMC reliably concentrates milk and the levels of milk concentration. These are groundbreaking studies; the first to study increases in fragile components such as


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stem cells in a mother’s own milk when concentrated by this process. For Specific Aim 2, MMIB has performed a small survey (55 respondents) with NICU staff in Boston. The majority of respondents believe the initiation of fortifiers added to expressed breast milk is a risk factor for development of necrotizing enterocolitis in infants receiving expressed human milk. Over 50% of respondents also agreed that concentrating mother’s own expressed milk to the desired caloric density without the need to add fortifiers would be of health benefit for the infant, 84% of respondents strongly agreed that increasing naturally occurring immunoglobulin content and other nutrients found in human milk would be of health benefit to infants, 76% would be interested in working with a device that would safely concentrate mother's own milk to the desired nutrient level (the remainder were neutral) and 69% of respondents thought families would want this method available to them as an option for their babies. The majority also agreed or strongly agreed that ‘my NICU would adopt such a system or device to concentrate expressed breast milk at the bedside (milk prep area/in unit) if research supports benefit.’ Given the initial responses, MMIB is confident in the proper execution and success of this study.

Study Procedures

Specific Aim 1

In this Specific Aim 1, our overall strategy is to show that targeted nutrients are concentrated and viable as shown through tests performed by outside laboratories. The verification of the nutrient content, given the performance of the HMC, will be accomplished through a six-step process.

Phase 1. Recruitment Participants will be recruited in two ways

1. A hospital facility- MMIB will be onsite to recruit participants, facilitate the consent form, intake form, scheduling and collection.

2. Mothers’ Milk Bank Northeast- They will be sending an email to their listserv asking for participation. The individuals will then contact us directly. The consent form and medical history interview will be conducted over the phone, the scheduling will be sent through email correspondence.

Phase 2. Consent and Medical History Interview Prior to participation, the consent will be reviewed either in person or over the phone. If it is over the phone, the document will be sent to the participant via email, Beth Schinkel or Elizabeth Nelson will review the document with the individual, and then the


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individual can sign and email the document back to MMIB. If the document is reviewed in person with MMIB, the individual can sign it then or can return it to us on site. The consent forms will be stored in a locked fire proof cabinet. The medical history will be collected one of two ways. If an in-person interview is possible, this is the preferred method. If the individual is pumping at home, the interview questions will be given over the phone. All documents will be secured in a locked fire proof cabinet at MMIB. The electronic data will be stored in a password protected file on an MMIB computer. The following questions will be asked during the interview:

Maternal date of birth First baby?: yes / no Active Maternal Diagnosis: Mastitis? Yes or No Infection requiring Antibiotic Yes or No Prescription: please clarify Diabetes Yes or No High blood pressure Yes or No Baby diagnosis: Allergy to milk/ formula Yes or No Baby born premature Yes or No Maternal medication exposure If yes what medication/ drug?: Baby's due date Baby's actual birth date Birth weight When did you first start pumping? How many times do you pump per 24 hrs (day 1) and how many times in 24 hrs do you pump now? When did your milk supply exceed baby's daily needs? (baby's age/ day of life) If you worked with a Lactation counselor was it more than once? Has your baby ever received supplemental fortifiers or formula in the hospital or at home? If yes do you recall what your baby was fed? If you have had extra milk what have you done with it in the past/ currently?


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Figure 2 Research plan for the quantification of nutrients in HM

Phase 3: Mother’s Milk Collection

The collection information (date and time) will be determined via email correspondence or in-person at the time of the medical history interview. On the collection date, mothers will pump their milk using their own breast pump method and device. They will pump per instructions provided by the manufacturer. Their sample will be collected into a breast milk bag. If they are onsite, a milk storage bag(s) will be offered. The collection bag will be either labeled by the participant with their ID number if they are collecting at home per email instructions or written by the participant or MMIB on the bag onsite using permanent marker. For both collections, a minimum of 30 milk samples will be collected (up to 40 milk samples), with each sample having a volume of 60ML or more. The milk will be collected one of three ways

a. A Motorcycle Club who works with the milk bank will pick up donated

milk b. MMIB will pick up the milk c. They will drop it off at a specified location

For participants offsite, their ID number will be used in reference to milk collection- no names will be used during pick up or associated with a specific address. At the time of drop off/pick up, the participant will be given the water bottle and payment for their time. If the participant would like fresh bags, two will be given to them at this time of transfer. For onsite individuals, they will also be provided water and fruit during the pumping session.

Phase 4: Concentration Each sample will be concentrated using the Human Milk Concentration Device. A portion of the milk will be extracted pre-concentration such that the nutrients can be compared pre and post concentration. The samples will be stored in -40deg ultra low freezer until sample distribution. Samples will be sent overnight on dry ice to the individual laboratories. All facilities work with Mother’s Milk and are aware of the recommended handling requirements created by the Human Milk Banking Association of North America. The remaining milk that has not be shipped to be sampled at the labs, will be stored in -40deg ultra low freezer for potential future use of samples, if given consent by the participant. These samples may be used for stem cell research or studies not yet known.

Phase 5: Nutrient Analysis The analysis of milk, the nutrient concentration

https://movingviolationsmc.com/


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pre and post concentration, will be performed at selected laboratories which specialize in the targeted nutrient(s) in mother’s milk (Figure 2). The following laboratories will be conducting the research-(1) The University of Amherst, Amy Burnside and CE Briere, will be evaluating living stem cells and their viability in human milk per and post concentration. (2) David Dallas at Oregon State University will measure the enzymes and enzymatic activity of bile salt stimulated lipase (BSSL), Plasmin/Protease Activity, and lysozymes from human milk samples at baseline and after concentration using ELISA plates. These studies demonstrate unique digestive benefit for preterm infants fed human milk concentrated with the HMC device given that these enzymes are denatured in pasteurized milk. They will run 60 samples in triplicate with 2 dilution levels which will provide 360 samples per plate. There will also be 10 standards in triplicate. (3) Lars Bode at the University of California San Diego will use ultra-high-pressure liquid chromatography to measure absolute and relative concentrations of human milk oligosaccharides (HMO) in samples at baseline and after concentration. Samples will be spiked with an internal standard to allow for absolute quantification. HMOs will be isolated by solid phase extraction and labeled at the reducing end with the fluorophore aminobenzamide. HMOs will be determined based on standard retention times as well as mass spectrometry and quantified based on standard response factors (4) Roger Dyer, at the Analytical Core for Metabolomics and Nutrition (ACMan) in Vancouver will coordinate the experiments to quantify the fatty acids of the milk pre and post concentration. They will analyze the fatty acid methyl esters by gas chromatography & flame ionization detection and identify and quantitate up to 28 individual fatty acids in each sample. They will analyze the free choline, glycerophosphocholine, betaine and phosphocholine by HPLC tandem mass spectrometry and analyze the milk phosphatidylcholine and sphingomyelin analysis by HPLC tandem mass spectrometry. (5) The Perrin Lab at the University of North Carolina Greensboro will work with MMIB to analyze mother’s milk (pre and post concentration) for the following components: lactoferrin (quantified by ELISA); secretory IgA (quantified by an activity ELISA); sodium (quantified by Ion Selective Electrode). There will be 60 samples in total (30 pre and 30 post concentration) evaluated by each laboratory. [nutrient analysis information taken from SBIR MMIB’s NIH Grant 1R43HD098737-01]

Phase 6: Analysis

The data will be analyzed and interpreted by the individual labs and a final report will be provided to MMIB. MMIB will collate the information, correlate the data, and the final interpretation will result in submitting for publication with all research labs reviewing the data before submission.


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Study Duration

Phase Duration (in weeks)

1-3 Milk Collection* 1

4: Milk Concentration 1

5: Nutrient Analysis 4

6: Analysis 4

Total 10

*assumes that the volume of milk is available within the patient population

Specific Aim 2

Phase 1: Gather documentation from hospitals on policy on milk management and breastfeeding MMIB will reach out to their contact at the respective hospital to have access to breastfeeding policy and milk management policy at that hospital. MMIB will request to have an interview with the individual involved with milk management.

Phase 2: Consent Prior to participation, the consent will be reviewed either in person or over the phone. If it is over the phone, the document will be sent to the participant via email, Beth Schinkel or Elizabeth Nelson will review the document with the individual, and then the individual can sign and email the document back to MMIB. If the document is reviewed in person with MMIB, the individual can sign it then or can return it to us on site. The consent forms will be stored in a locked fire proof cabinet.

Phase 3: One-on-One Interview MMIB will conduct a 15-minute interview with an identified individual within the hospital who is familiar and practices milk management.

Phase 4: Observation MMIB will observe the milk management process in action. The time and duration of the observation will be dependent on the hospital’s milk management practice- milk room, bedside, nurse’s station.


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Study Duration

Phase Duration (in weeks)

One: Documentation Collection 1

Two: One-on-one Interview 6

Three: Observation

Total 8

Inclusion/Exclusion Criteria

Specific Aim 1

Inclusion Criteria o Females (18 years and older) who are providing human milk for their infant,

(infants must be less than 4 weeks old) o Mothers must have adequate milk supply (750 ml ( = 25 ounces/day) or more per

day) or be ‘pumping and dumping their milk’ for a medical reason (milk cannot be provided for feeding baby yet).

Exclusion Criteria: Women who are/have (any may apply):

• less than 18 years of age

• pregnant

• non-English speakers

• non-breastfeeding mothers

• diagnosed with any acute or chronic issues (eg. cardiovascular, diabetes, etc)

• significant challenges with breastfeeding

• any issues with breast or nipple tissue

Specific Aim 2

Inclusion Criteria Individuals who are

• Working in a NICU

• In contact and part of the milk management process

Exclusion Criteria Individuals who are


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• Do not work in a NICU

• Not In contact and part of the milk management process

• Non-English speakers

Drugs/Substances/Devices

a. The rationale for choosing the drug and dose or for choosing the device to be used. n/a

b. Justification and safety information if FDA approved drugs will be administered for non-FDA approved indications or if doses or routes of administration or participant populations are changed.

No drugs will be administered for our study. c. Justification and safety information if non-FDA approved drugs without an IND

will be administered.

No drugs will be administered for our study.

Study Statistics

Specific Aim 1

Primary Outcome Variables

1. Initial Volume of Milk

2. Final Volume of Milk

3. Nutrient analysis pre-concentration

4. Nutrient analysis post concentration

5. % Difference between nutrient and volume concentration

Secondary Outcome Variables 1. Volume of milk concentrated at t=30 minutes 2. Cross reference nutrient information by the following variables (from medical

history interview) a. Maternal date of birth b. First baby c. Active Maternal Diagnosis: d. Mastitis


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e. Infection requiring Antibiotic f. Diabetes g. High blood pressure h. Baby’s Allergy to milk/ formula i. Baby born premature j. Maternal medication exposure k. Baby's due date l. Baby's actual birth date m. Birth weight n. When mother first start pumping? o. How many times mother’s pump per 24 hrs (day 1) and how many times

in 24 hrs do thye pump now? p. When their milk supply exceeded baby's daily needs? (baby's age/ day of

life) q. If a Lactation counselor was used? r. Baby’s supplemental fortifiers or formula in the hospital or at home?

Note: If consent is provided to use the remaining samples for future use, the variables might change given the testing that is performed.

Statistical Plan This study will include more than 30 samples. This estimate is based on the following assumptions: 1. The study will measure the difference between the paired data results

2. Assuming a type-I error rate of 5% and 80% power, this study will need 27 samples

to measure a statistically significant difference between the concentrated milk and unconcentrated milk

When the study is ~100% complete, we will measure the preliminary results by: 1. For dependent data, in which measurements were taken on the same HMC

concentration device with two different samples, paired t-tests will be used to determine statistically significant differences.

2. Group data can also be compared between the unconcentrated milk and concentrated milk using unpaired t-tests.

3. Data can be separated into categories based on medical history interview to

determine if there are trends identified for potential future studies.


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Specific Aim 2 The data from this aim will be qualitative.

Primary Outcome Variables n/a

Secondary Outcome Variables n/a

Statistical Plan n/a

Early stopping rules.

Specific Aim 1 If the human milk concentration device has a defect in manufacturing, the HMC device will be evaluated to determine possible causes of error and potentially decide to discontinue testing.

Specific Aim 2 n/a

Confidentiality and Privacy of Subjects

Specific Aim 1

The following methods will be used to maintain confidentiality:

• An ID will be provided to every participant. This ID number will be used exclusively. The ID will be placed on

o Milk Sample Collection Bottle/Bag o Pre and post concentration samples o Medical History Interview

• All documents will be stored in a locked filing cabinet and will not contain identifying information

• The medical history interview will only be shared with individuals and organization that conduct or watch over this research, including:

o The research sponsor


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o People who work with the research sponsor o Government agencies, such as the Food and Drug Administration o The Institutional Review Board (IRB) that reviewed this research

• If possible, the $10 payment for participation will be given in cash to the participant such that the payment will not have to be sent to the individual.

• The database used for this study will be password protected and maintained in a secure fashion

• Data from the study many be stored for future use but will remain securely stored on a password protected computer

• If milk is being pick up from a specified location, the name of the individual will not be disclosed. The ID number will serve as the tracking mechanism

Specific Aim 2 For all interviews and observations, only first names will be recorded. All interview information collected will be stored in a locked fire proof filing cabinet.

Risks

Specific Aim 1

a. Medical risks, listing all procedures, their major and minor risks, and expected frequency.

Risks Causes Frequency expected

Potential harm Step to minimize risks

Biohazard

Exposure

Improper handling of

mother’s milk leading to slashed of

milk in eyes, skin contact

<1% low

Research labs testing the milk

have prior experience with

testing milk, Gloves, glasses, and gowning will

be used during the concentration

process. Universal precautions; milk will be stored per

usual care


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Specific Aim 2

a. Medical risks, listing all procedures, their major and minor risks, and expected frequency.

none

Plan for reporting unanticipated problems or study deviations.

Any unanticipated problems or study deviations will be documented in writing by the technical representative and brought to the attention of the PI.

Legal risks such as the risks that would be associated with breach of confidentiality.

None at this time.

Financial risks to the participants.

None at this time

Benefits a. Description of the probable benefits for the participant and for society.

I) Individual

N/A II) Society

Increasing the percentage of mother's own milk transferred to her baby may improve health for baby and mother as baby may be exclusively fed mother's own milk. Particularly for mother's who have abundant milk supply and whose baby requires concentrated feedings that otherwise would require the addition of additives from cow's milk or pooled HM donor sourced fortifiers. Potential benefits of feeding solely mother's own milk, that require additional research to prove, may be increased immune protection of a fragile preterm infant, increased transfer of hormones and digestive enzymes that may impact the microbiome and long term health of the baby and reduced risk of feeding intolerance and potentially Necrotizing Enterocolitis.


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Payment and Remuneration

Specific Aim 1

1. Participants a. Compensation will be offered to participants- $10/sample b. Provided access to fruit and water during pumping session c. MMIB water bottle d. Breast milk storage bag if on site-

https://www.buybuybaby.com/store/product/medela-6-oz-breast-milk-storage-bags/3333415

2. Nutrient Analysis a. Laboratories analyzing the data will be paid according to specified

contract.

Specific Aim 2

none

Costs a. Detail costs of study procedure(s) or drug (s) or substance(s) to

participants and identify who will pay for them. Participants will be asked to provide their own pumping bag for collection when offsite. If requested, an unused milk collection bag(s) will be given to them at the time of transfer to MMIB. All cost of the nutrient analysis used in this trial will be paid by MMIB, Inc.


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References

1. Ballard, O., & Morrow, A. L. (2013). Human Milk Composition. Pediatric Clinics of North America,60(1), 49-74. doi:10.1016/j.pcl.2012.10.002 2.Meier, P. P., Patel, A. L., & Esquerra-Zwiers, A. (2017). Donor Human Milk Update: Evidence, Mechanisms and Priorities for Research and Practice. The Journal of Pediatrics, 180, 15–21. http://doi.org/10.1016/j.jpeds.2016.09.027 3. Bertino E., Giuliani F., Occhi L., Coscia A., Tonetto P., Marchino F., Fabris C. Benefits of donor human milk for preterm infants: Current evidence. Early Hum. Dev. 2009;85:S9–S10. doi: 10.1016/j.earlhumdev.2009.08.010. 4. Moro GE, Arslanoglu S, Bertino E, Corvaglia L, Montirosso R, Picaud JC, et al. XII. Human milk in feeding premature infants: Consensus statement. J Pediatr Gastroenterol Nutr. 2015;61:S16–9 5. Herrmann, K., & Carroll, K. (2014). An Exclusively Human Milk Diet Reduces Necrotizing Enterocolitis. Breastfeeding Medicine, 9(4), 184–190. http://doi.org/10.1089/bfm.2013.0121 6.Unger SL, Gibbins S, Kiss A, O’Connor DL. Donor milk reduces necrotizing enterocolitis but does not improve neurodevelopment of very low birthweight (VLBW) infants at 18 months corrected age. Paper presented at: Pediatric Academic Society; 2016 April 30–May 3; Baltimore, MD 7. Johnson TJ, Patel AL, Bigger HR, Engstrom JL, Meier PP. Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants. Neonatology. 2015;107:271–6. [PMC free article] [PubMed] 8. Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis.Microbiome. 2017;5:31 9. Sherman MP, Miller MM, Sherman J, Niklas V. Lactoferrin and necrotizing enterocolitis. Curr Opin Pediatr. 2014;26:146–50. [PubMed] 10. Johnson et al. Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants. Neonatology. 2015;107(4):271-6. doi: 10.1159/000370058. Epub 2015 Mar 3.

http://doi.org/10.1016/j.jpeds.2016.09.027

http://doi.org/10.1089/bfm.2013.0121

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458214/

https://www.ncbi.nlm.nih.gov/pubmed/25765818

https://www.ncbi.nlm.nih.gov/pubmed/24503532

Efficacy of Human Milk Concentration Device: A Nutrient...

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