The Influence of Nutritional Status on Brain Development: Benefits of Exclusive Breastfeeding

Round 1

Reviewer 1 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

This study is highly commendable for its review of carefully selected literatures from a considerable number of articles, but there are still some unclear points.

 

Line 101-108 should be deleted because it has already been stated.

 

The review included studies that suggested a positive association between breast milk and neurocognitive development; which implied that only the benefit of breast milk may be concluded and the negative study results are not reflected. Does this not fully achieve the purpose of this review?

 

The discription of discussion is an only extension of the results of this study and is not a discussion. You should be discussed by using studies other than Ref No. 12-22, which were the subjects of the analysis of this study.

Author Response

Reviewer 1#

This study is highly commendable for its review of carefully selected literatures from a considerable number of articles, but there are still some unclear points. 

Answer: We would like to extend our heartfelt thanks for taking the time to share your valuable comments with us. Ensuring that we meet and exceed your expectations is our top priority. We are committed to enhancing the quality of our study and your input is instrumental in achieving this goal. Your feedback is immensely appreciated and helps us strive for continuous improvement. For clarity purposes, we attached the revised manuscript for your revision.

 

 Line 101-108 should be deleted because it has already been stated.

Answer: We thank you for the comment. The text was removed from the revised version of the manuscript.

 

The review included studies that suggested a positive association between breast milk and neurocognitive development; which implied that only the benefit of breast milk may be concluded and the negative study results are not reflected. Does this not fully achieve the purpose of this review?

Answer: Thank you for your insightful comment. Our review aimed to provide an evidence-based overview of the potential benefits of exclusive breastfeeding on neuropsychomotor development. We focused on studies exploring the positive associations between breast milk and neurocognitive development, as these comprise a significant portion of the current literature and offer valuable insights into the mechanisms behind these benefits.

However, we acknowledge that including studies with negative or neutral findings is equally important for a balanced perspective. The review's methodology may have inadvertently emphasized studies with positive outcomes, possibly due to the available literature at the time. We did recognize the limitations of our review, including the lack of quantitative techniques and standardized methodologies, which could have provided a more comprehensive analysis.

In light of your feedback, we agree that incorporating studies with negative or neutral results would enhance the robustness of the review. We plan to include a broader range of studies for future work, ensuring a more balanced representation of the existing evidence. This will help us understand the full spectrum of the relationship between exclusive breastfeeding and neurocognitive development.

 

 

 

The discription of discussion is an only extension of the results of this study and is not a discussion. You should be discussed by using studies other than Ref No. 12-22, which were the subjects of the analysis of this study.

Answer: We appreciate your valuable comments and feedback. We appreciate your observation that the current discussion primarily extends the results of the studies included in our analysis. We understand the importance of incorporating a broader range of literature to provide a more comprehensive and critical discussion.

In discussing the revised manuscript, we included studies beyond those referenced in our analysis (Ref. 12-22). This allowed us to compare and contrast our findings with a wider body of research, including studies with different methodologies, populations, and outcomes. By doing so, we aim to enrich the discussion and offer a more nuanced interpretation of the effects of exclusive breastfeeding on neuropsychomotor development.

We also address potential confounding factors and alternative explanations presented in other studies, which may not have been the focus of our review but are relevant to understanding the overall impact of breastfeeding on neurodevelopment. All these alterations are highlighted in green in the revised document (Lines 353 to 395, and Lines 431 to 438).

Author Response File: Author Response.pdf

Reviewer 2 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

a narrative review on a relevant topic

Author Response

Reviewer 2#

Comments and Suggestions for Authors: a narrative review on a relevant topic

Answer: Thank you for your feedback regarding our paper. We attached the revised version of the manuscript for your revision.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

Thanks for your revision and the courteous reply. I have no additional comments to the content of the text. Please proofread the reference numbers only.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I have read this paper with interest, and with a background on clinical perinatal research, including aspects on lactation. I therefore value the topic, and its clinical epidemiological relevance. In this way, this paper is rather confirmatory, based on a structured search of papers a published on PubMed.  

I have the personal impression that the paper intends to covers both associations related to the brain and neurocognitive development, as well as claimed mechanisms (imaging, in vitro work, mRNA) to explain these differences in outcome. However, this is not really clear as the search strategy, and the subsequent assessment of the retrieved ‘hits’ (PubMed only). How have hits been assessed, and how have retained papers be assessed (extraction, quality assessment should be done, were these processes done by a single person, or two persons (who, what and when).

I recommend to subdivide the results by the ‘type of outcome’ to further provide perspective in the paper as a potential alternative approach to improve the current version of the paper.

Specific comments:

Figure 1: typo, PubMe should read PubMed

Line 132: support neural growth (suggest to add here also connections, and myelinization)

Line 138: myelin membranes formation, I think that ‘myelination’ is more accurate

Line 168: potential epigenetic effects present in human milk: please rephrase

Author Response

Reviewer 1#

I have read this paper with interest, and with a background on clinical perinatal research, including aspects on lactation. I therefore value the topic, and its clinical epidemiological relevance. In this way, this paper is rather confirmatory, based on a structured search of papers a published on PubMed. 

Answer: We express our gratitude for your valuable comments. It is our utmost priority to fulfill your expectations while enhancing the quality of our study.

I have the personal impression that the paper intends to covers both associations related to the brain and neurocognitive development, as well as claimed mechanisms (imaging, in vitro work, mRNA) to explain these differences in outcome. However, this is not really clear as the search strategy, and the subsequent assessment of the retrieved ‘hits’ (PubMed only). How have hits been assessed, and how have retained papers be assessed (extraction, quality assessment should be done, were these processes done by a single person, or two persons (who, what and when).

Answer: Thank you for your insightful question and for recognizing the importance of clarity in our study's methodology. We appreciate your keen observation regarding the need for a clear and detailed explanation of our search strategy, assessment process, and how we investigated the associations between breastfeeding and neurocognitive development. Ensuring transparency and rigor in our methodology is paramount to the validity and reliability of our findings. In the revised version of the manuscript, we included more detailed methodological aspects applied to prepare our review, which are highlighted in red in the document (Lines 78 to 120).

As outlined in our study, the search was conducted using the PubMed database with specific keywords ("Brain" AND "Growth" OR "Development" AND "Breastfeeding") combined using Boolean operators ("AND" and "NOT"). This strategy was designed to encompass a broad range of studies relevant to both neurocognitive development and the underlying mechanisms facilitated by breastfeeding. The initial search yielded 15,412 articles, then filtered based on our eligibility criteria. This comprehensive review included only studies published between 2013 and 2024, written in English. It focused on the positive association between breast milk and neurocognitive development, excluding those that dealt with diseases, maternal health, or intervention strategies.

            We would like to clarify that PubMed was the only database platform applied in our search because it is the most extensively used database and search engine in the biomedical and healthcare fields. PubMed comprises more than 37 million citations for biomedical literature from MEDLINE, life science journals, and online books, making it an unparalleled resource for comprehensive and up-to-date scientific information (10.5195/jmla.2019.433; 10.1371/journal.pone.0281422; 10.1371/journal.pbio.2005343; 10.1080/17521740701702115). This extensive coverage ensures that we can access a wide range of high-quality, peer-reviewed articles pertinent to our study on the effects of exclusive breastfeeding on neurocognitive development.

 

By leveraging PubMed's robust search capabilities and extensive database, we aimed to capture a comprehensive set of relevant studies. Additionally, PubMed's integration with MEDLINE and its focus on life sciences and biomedical topics align closely with the specific aims of our research, providing us with a highly relevant and specialized pool of literature. We believe that utilizing PubMed allowed us to maintain a high standard of quality and relevance in the articles we reviewed, thereby strengthening the overall rigor and reliability of our findings. Nonetheless, we acknowledge the value of incorporating multiple databases in future research to ensure an even broader scope of literature.

            Following, two independent researchers screened the titles and abstracts of the initial search results to ensure a thorough and unbiased selection process. Articles that did not meet the inclusion criteria were excluded at this stage. The remaining articles were reviewed in full to confirm their relevance. Any discrepancies between the two reviewers were resolved through discussion and, when necessary, consultation with a third researcher. Relevant data from the selected studies were meticulously extracted and grouped into a table. The extracted information included the author's name, year of publication, study population details, evaluation methodology, and specific outcomes related to neurocognitive development and breastfeeding. By adhering to this methodology, our study has endeavored to provide robust evidence on the benefits of exclusive breastfeeding for neurocognitive development. This detailed explanation clarifies our search strategy, assessment process, and the mechanisms explored, thereby addressing your concerns comprehensively.

 

I recommend to subdivide the results by the ‘type of outcome’ to further provide perspective in the paper as a potential alternative approach to improve the current version of the paper.

Answer: Thank you for your valuable feedback and for suggesting an alternative approach to enhance the presentation of our results. We appreciate your recommendation to subdivide the results by the type of outcome, as this can indeed provide clearer insights and a more structured perspective on the findings. This approach would allow readers to more easily identify and interpret the specific benefits and mechanisms associated with exclusive breastfeeding. The revised manuscript incorporates the subdivision based on the type of results, as follows:

3.1 Potential mechanisms involved in the positive association between breastfeeding       and neurodevelopment (Page 6)

3.2 Neurocognitive benefits observed in exclusively breastfed children (Page 7)

            We also polish the discussion in order to better explore the findings of selected studies. All these alterations are highlighted in red in the revised document.

 

 

 

Specific comments:

Figure 1: typo, PubMe should read PubMed

Answer: Thank you for your comment. It was corrected.

 

Line 132: support neural growth (suggest to add here also connections, and myelinization)

Answer: Thank you for your comment. It was added and marked in red (Line 164).

 

Line 138: myelin membranes formation, I think that ‘myelination’ is more accurate

Answer: Thank you for your comment. It was corrected and marked in red (Lines 295 and 300).

 

Line 168: potential epigenetic effects present in human milk: please rephrase

Answer: Thank you for your comment. It was rephrased and highlighted in red in the document (Page 6, lines 200 to 202).

 

Reviewer 2 Report

Comments and Suggestions for Authors

Although the topic of this review examining the effects of breast milk nutrition on the brain development of the child is interesting, the structure of this paper is immature and does not reach the level of publication.

The main fault of this review is that the data analysis is not described in Method; Chart 1 lists the papers included, but does not analyze these results, so it remains uncertain what was revealed in this review. Within the Discussion, there is a detailed description of the included papers. This is to be analyzed within the results, not the discussion. In the conclusion, the benefit of breast milk compared to formula is mentioned, but not described in the results. Therefore, the structure of the paper is not consistent.

Minor revisions:
Inclusion criteria for this review should be stated within the Methods.
Citation numbers should be added to lines 99-116 in Results.

Author Response

Reviewer 2#

Although the topic of this review examining the effects of breast milk nutrition on the brain development of the child is interesting, the structure of this paper is immature and does not reach the level of publication.

Answer: Thank you for your feedback regarding our paper. We recognized the need for improvements to meet publication standards and have addressed your concerns accordingly. We undertook a comprehensive revision of the manuscript, reorganizing the content to enhance clarity and coherence. The introduction was refined to clearly outline the study's objectives and scope, while the results section was restructured to categorize findings by outcome type, as you suggested. This restructuring provided a more systematic presentation of the data.

We strengthened the analysis and interpretation of the results, offering a more detailed discussion of the mechanisms through which breastfeeding influences neurodevelopment. We also improved the presentation and style of the manuscript, ensuring consistency and enhancing readability. By incorporating your constructive feedback, we aimed to enhance the overall quality of the paper. All these alterations are highlighted in red in the revised document.

 

The main fault of this review is that the data analysis is not described in Method;

Answer: Thank you for your insightful question and for recognizing the importance of clarity in our study's methodology. We appreciate your keen observation regarding the need for a clear and detailed explanation of our search strategy, assessment process, and how we investigated the associations between breastfeeding and neurocognitive development. Ensuring transparency and rigor in our methodology is paramount to the validity and reliability of our findings. In the revised version of the manuscript, we included more detailed methodological aspects applied to prepare our review, which are highlighted in red in the document (Lines 78 to 120).

As outlined in our study, the search was conducted using the PubMed database with specific keywords ("Brain" AND "Growth" OR "Development" AND "Breastfeeding") combined using Boolean operators ("AND" and "NOT"). This strategy was designed to encompass a broad range of studies relevant to both neurocognitive development and the underlying mechanisms facilitated by breastfeeding. The initial search yielded 15,412 articles, then filtered based on our eligibility criteria. This comprehensive review included only studies published between 2013 and 2024, written in English. It focused on the positive association between breast milk and neurocognitive development, excluding those that dealt with diseases, maternal health, or intervention strategies.

            Following, two independent researchers screened the titles and abstracts of the initial search results to ensure a thorough and unbiased selection process. Articles that did not meet the inclusion criteria were excluded at this stage. The remaining articles were reviewed in full to confirm their relevance. Any discrepancies between the two reviewers were resolved through discussion and, when necessary, consultation with a third researcher. Relevant data from the selected studies were meticulously extracted and grouped into a table. The extracted information included the author's name, year of publication, study population details, evaluation methodology, and specific outcomes related to neurocognitive development and breastfeeding. By adhering to this methodology, our study has endeavored to provide robust evidence on the benefits of exclusive breastfeeding for neurocognitive development. This detailed explanation clarifies our search strategy, assessment process, and the mechanisms explored, thereby addressing your concerns comprehensively.

 

Chart 1 lists the papers included, but does not analyze these results, so it remains uncertain what was revealed in this review.

Answer: Thank you for highlighting this important point. We acknowledge that Table 1 (previously named as “Chart”) lists the included studies but does not provide a detailed analysis of their results, which are highlighted in red in the revised document (Lines 325 to 360, but also in other parts of the manuscript). To address this, we have included a comprehensive discussion in the revised manuscript, which analyzes the findings from the studies listed in Table. This discussion provides an overview of the key outcomes and implications of each study, including the specific contributions of various bioactive compounds in breast milk, the effects of exclusive breastfeeding on brain development and cognitive performance, and the observed mechanisms through which breastfeeding influences neurodevelopment. By incorporating this analysis, we aim to clarify the overall insights gained from the review and provide a clearer understanding of the evidence presented in the included studies.

 

Within the Discussion, there is a detailed description of the included papers. This is to be analyzed within the results, not the discussion.

Answer: Thank you for your comment. We moved the description of the included papers to a separate section named “Results”. We also subdivided the results by the type of outcome, as this can indeed provide clearer insights and a more structured perspective on the findings. This approach would allow readers to more easily identify and interpret the specific benefits and mechanisms associated with exclusive breastfeeding. The revised manuscript incorporates the subdivision based on the type of results, as follows:

3.1 Potential mechanisms involved in the positive association between breastfeeding       and neurodevelopment (Page 6)

3.2 Neurocognitive benefits observed in exclusively breastfed children (Page 7)

            All these alterations are highlighted in red in the revised document.

 

In the conclusion, the benefit of breast milk compared to formula is mentioned, but not described in the results. Therefore, the structure of the paper is not consistent.

Answer: Thank you for pointing out this inconsistency. We appreciate your careful review of the manuscript. In response to your feedback, we have revised the paper to ensure that the conclusion aligns with the results presented.           All these alterations are highlighted in red in the revised document (Lines 380 to 400).

The revised manuscript now includes a more detailed discussion of how the results support the benefits of breast milk compared to formula feeding. Specifically, we have integrated findings from the studies in Table 1, highlighting key results such as improved brain white matter development, enhanced cognitive performance, and superior neural connectivity in exclusively breastfed infants. By directly linking these findings to our conclusion, we aim to provide a cohesive narrative demonstrating how the evidence supports the advantages of breastfeeding over formula feeding.

We have updated the manuscript to reflect these changes, ensuring that the conclusion accurately represents the results and provides a consistent and comprehensive overview of the study’s findings.

 

Minor revisions:

Inclusion criteria for this review should be stated within the Methods.

Answer: Thank you for your comment. The inclusion criteria were provided in the revised document, which are highlighted in red in the document (Section 2.2 “Eligibility criteria and study selection criteria”, lines 90 to 108). More specifically, the criteria for this study aim to select high-quality systematic reviews, narrative reviews, and observational studies that delve into the profound impact of exclusive breastfeeding on the neurocognitive development of infants and young children. These chosen studies should be published in the English language and must present compelling evidence that illustrates the myriad benefits of exclusive breastfeeding for brain development. Additionally, these studies should thoroughly explore and elucidate the intricate mechanisms through which breastfeeding influences neurocognitive outcomes, encompassing the pivotal roles of micronutrients, bioactive compounds, and epigenetic factors. Studies that focus on diseases unrelated to neurodevelopment, prioritize maternal health over child development, or predominantly address interventions aimed at promoting breastfeeding rather than its effects on neurocognitive development will be excluded from consideration.

 

Citation numbers should be added to lines 99-116 in Results.

Answer: Thank you for your comment. It was added and highlighted in red in the document (Lines 131 to 149).