PONE-D-21-01879

Human Milk-Based Fortifier is Associated with Less Alteration of Milk Fat Globule Size than Cow Milk-Based Fortifier

PLOS ONE

Dear Dr. Mizuno,

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Academic Editor

PLOS ONE

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4. Thank you for stating the following in the Financial Disclosure section:

'KH receives speaker honoraria from Prolacta Bioscience.

Prolacta Bioscience (www.prolacta.com) provided the product for use in this study but

was not involved in the study design, data collection or analysis, performance of the

study, outcomes, decision to publish, or manuscript writing.'

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Additional Editor Comments (if provided):

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study aimed to assess the change of the MFG size with the fortification of a human milk-based or a cow milk-based fortifier. Changes in the particle size might associate with feeding intolerance. This is of great relevance, particularly for low-birth-weight or preterm infants.

Over the manuscript, there are some inconsistencies in the grammar, as well as some repetitiveness in some parts. I would suggest authors revise the manuscript.

The Introduction section seems very broad. In this part, the authors should describe more about the relevance of the MFG size, the differences in composition of the two fortifiers, etc. This would create a greater interest in the reader.

Regarding the methodology, was the MGF size measurement done in duplicate, or were they single measurements? What software was used to conduct the statistical analyses?

Could the author summarize the demographic characteristics of the donors (e.g. age, weight, BMI)?

The results section mentions three different figures which were not part of the manuscript. I wonder if there was an issue with the website/system. I can not discuss much about the information associated with the figures.

Table 1 could include more information to make it more comprehensive. For example, could you add the number of samples in each group (n=), as well as the p values for the differences within and between groups?

The discussion summarizes the findings and the impact on MFG sizes. Although the authors discuss some of the possible mechanisms, they could further explain how human milk-based or a cow milk-based fortifier changes the size and structure of the MFG and how the consumption affects the feeding tolerance in infants consuming these fortifiers.

Reviewer #2: Review Comments to the Author

This paper aimed at to evaluate the HMBF and CMBF on the MFG, and to explain it impact on feeding tolerance. The result sounds interesting, however, the paper still explain the detail of the test and how it works, more data need before it could accept. Question is list below:

1. For the particle size of fat globule, many parameter many effect the result, such as p

H, Ca and casein content in milk. You should add this data in the paper.

2. Line 76-80, you collected human milk from 9 monther, do you mixed the 9 sample together or

Separated? If you separate, does all sample the protein is 2.9g/100ml? for the line 79, more information about CMBF is need, company, composition.

3. Line 82-83, after you mixed together, you test the size in 0, 1, 24, 48h. Does the sample is put in refrigerator? What’s temperature you keep the sample?

4. Excepted the particle size, such as the scanning electron microscope is need to show the difference of the samples.

5. The figures is not show in the paper, please added it.

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Reviewer #1: No

Reviewer #2: Yes: Daxi Ren

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Human Milk-Based Fortifier is Associated with Less Alteration of Milk Fat Globule Size than Cow Milk-Based Fortifier

PONE-D-21-01879R1

Dear Dr. Mizuno,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Juan J Loor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you to the authors for addressing the comments and suggestions. The manuscript has improved.

There are only some minor things that I would suggest. The numbers for the citations should be before the point or commas just so there are no blank spaces. The title of Figure 3 should begin with a capital letter.

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Miriam Aguilar-Lopez

Reviewer #2: No