Review Reports - Down Syndrome and Obesity Management: Lifestyle Observations Made in the Framework of the GO-DS21 Project and Clinical Recommendations

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Title: Down syndrome and obesity management: lifestyle observations made in the framework of the GO‑DS21 project and clinical recommendations.

Gomis‑González et al. presented an observational study conducted across three European sites within the EU Horizon 2020 GO‑DS21 project, aiming to highlight key insights for developing effective prevention and management strategies for overweight and obesity in individuals with Down syndrome. As the authors emphasize, there is a lack of scientific evidence in this area, with most available studies focusing on children. By including a population aged 12 to 45 years, this study offers an important additional perspective, as it captures data from adolescents and provides much-needed information on adults with Down syndrome, an age group for which evidence on obesity management remains particularly scarce.

The main findings indicate an early onset of multimorbidity in individuals with Down syndrome, an increased risk of overweight and obesity beginning in adolescence, a strong influence of family context, particularly parental BMI, on weight outcomes, and the important role of diet quality and physical activity in both metabolic and cognitive health.

The manuscript is easy to read and maintains scientific rigor throughout. It may be of general interest to the journal's readers; however, I have some concerns presented below. I ask that the authors specifically address each of my comments in their response.

INTRODUCTION

The introduction is nicely written and emphasizes the problem. However, it could be helpful for readers if the authors added a bit more detail about the study methods. Even a brief note on the data-collection period or a mention of the participating sites would make the study easier to understand, while still maintaining the concise format expected for a Communication article.

RESULTS

The Results section is informative and covers several relevant domains; however, it may benefit from a summary that highlights the key quantitative findings. In particular, providing the exact prevalence of overweight and obesity in the studied Down syndrome cohort would help readers better understand the magnitude of the problem and contextualize the subsequent discussion.

The authors may consider adding a concise summary table outlining the study population’s key characteristics (e.g., age range, sample size, sex distribution, BMI), which could further enhance clarity and help readers quickly grasp the cohort’s composition. Although such a table is not mandatory for a Communication article, in my view, it would provide a more straightforward overview of the results section.

DISSCUSION

It may be helpful to add a short introductory paragraph that synthesizes the main findings before presenting them as bullet points. Figure 1 is clear, well-structured, and effectively summarizes the key points.

With these minor revisions incorporated, the manuscript will align well with the scope and standards of Nutrients and will make a valuable contribution to the field.

Comments for author File: Comments.pdf

Author Response

REVIEWER 1

Comments and Suggestions for Authors

Title: Down syndrome and obesity management: lifestyle observations made in the framework of the GO‑DS21 project and clinical recommendations.

Thank you very much for your insightful and positive feedback on our manuscript. We sincerely appreciate your recognition of the study’s importance, particularly its focus on the underserved population of adolescents and adults with Down syndrome.

We are pleased that you found the manuscript easy to read and scientifically rigorous. We acknowledge your comments and concerns, and we are committed to addressing each of them specifically to improve the quality of our work.

We provide a detailed, point-by-point response to all your suggestions in the revised version of the manuscript.

INTRODUCTION

We thank the reviewer for the constructive comments about the details on study methods.

In response, we have include a brief Methods section in the manuscript, in line with the concise format of a Communication article. This new section provides additional details on the participating centers, the recruitment period), and the data-collection procedures.

We believe that these additions improve the transparency of the study design and the origin of the data, while maintaining the brevity required for this article format.

This new section can be found at page 2, line 66.

RESULTS

Thank you very much for your feedback on the results section of the manuscript.

Regarding your suggestion, to further contextualize the results and the resulting guidelines, we would like to clarify a key point in our methodology:

While the findings from our observational study within the GO-DS21 project provide crucial primary data to elaborate these guidelines, the prevention and management guidelines we present are not derived solely from this specific cohort but also from two observational studies performed from UK electronic health registers (presently referenced in the Introduction).

The guidelines have been developed by integrating our empirical results with other existing scientific literature and established clinical sources. This evidence-based approach ensures that the recommendations are robust, generalizable, and supported by the broader scientific context beyond our immediate findings. For these reasons, we believe that focusing exclusively on the quantitative prevalence data from our specific cohort could inadvertently narrow the scope of the proposed guidelines.

We thank the reviewer for this helpful suggestion. In response, we have added a concise summary table outlining the key characteristics of the GO-DS21 study population (including sample size, age, sex distribution, and BMI).

This table has been included at the end of the newly added Methods section to provide readers with a clear and straightforward overview of the cohort’s composition, while maintaining the concise format required for a Communication article.

DISCUSION

We sincerely thank the reviewer for this constructive suggestion.

We agree that a synthesis paragraph helps to frame the conclusions more effectively for the reader. Accordingly, we have added a short introductory summary before the bulleted points to integrate the main findings provide a clearer transition into the specific recommendations.

This additional introductory summary before the core findings can be found at page 4, line 190.

With these minor revisions incorporated, the manuscript will align well with the scope and standards of Nutrients and will make a valuable contribution to the field.

We sincerely thank the reviewer for this positive assessment and for the constructive suggestions provided throughout the review process.

We have carefully incorporated the recommended revisions and believe that these changes have strengthened the manuscript. In the few instances where a suggestion was not incorporated, we have provided a clear justification in our response, explaining our rationale.

We appreciate the reviewer’s time and thoughtful feedback, which have helped us improve the clarity and overall quality of our work.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

This manuscript addresses an important and timely topic and is generally well written. However, major revisions are required before it can be reconsidered for publication.

The main issues that need to be addressed are:

Clarify the primary aim and scope of the communication.
It is currently unclear whether the manuscript intends to present observational findings, a conceptual synthesis, or clinical recommendations. Please clearly define the focus and align the structure and conclusions accordingly.
Explicitly define the limits of the analysis.
Several sections use language that may suggest causality or clinical guidance. The observational nature of the evidence, the absence of intervention data, and the limits of inference should be clearly acknowledged, particularly regarding diet–cognition associations.
Improve transparency regarding data sources and methodology.
Even for a short communication, readers should be able to understand the origin of the data that underpin the conclusions and recommendations.

Addressing these points will substantially strengthen the scientific rigor, clarity, and interpretability of the manuscript.

Kind regards,

Author Response

REVIEWER 2

Dear Authors,

This manuscript addresses an important and timely topic and is generally well written. However, major revisions are required before it can be reconsidered for publication.

We sincerely thank the reviewer for the positive assessment and recognizing the importance of the topic. We also appreciate the constructive feedback provided and we have carefully addressed the requested major revisions to improve the quality of the manuscript.

The main issues that need to be addressed are:

Clarify the primary aim and scope of the communication.
It is currently unclear whether the manuscript intends to present observational findings, a conceptual synthesis, or clinical recommendations. Please clearly define the focus and align the structure and conclusions accordingly.

We thank the reviewer for this insightful comment.

We have revised the introduction to explicitly state that the primary aim of this brief communication is to provide clinical recommendations for individuals with Down syndrome and their families. We have clarified that these recommendations are built upon a synthesis of existing literature and our own observational data from the GO-DS21 project.

These new information can be found in the Introduction section, page 2 line 48:

“To address this gap, this brief communication aims to provide practical clinical recommendations for individuals with DS and their families to support weight management and obesity prevention”

And also in a brief sentence at the end of the Introduction (page 2, line 62):

“The final aim is to offer a practical framework for the prevention and treatment of overweight and obesity in Down syndrome population”.

We would like to highlight that the Discussion section was already structured point-by-point to present the findings in a clear and actionable manner, supported by a visual summary in Figure 1 to ensure accessibility for families and clinicians.

However, in response to the reviewer’s suggestion to better clarify the clinical focus, we have slightly refined the wording of these points to emphasize their nature as clinical recommendations rather than just observational findings. We believe these minor adjustments, combined with the clarified aim in the Introduction, now provide the clear and consistent focus the reviewer requested while maintaining the original organized structure of the manuscript.

Explicitly define the limits of the analysis.
Several sections use language that may suggest causality or clinical guidance. The observational nature of the evidence, the absence of intervention data, and the limits of inference should be clearly acknowledged, particularly regarding diet–cognition associations.

We thank the reviewer for this comment. The association between diet and cognition has been further toned down following the reviewer suggestions and we have now explicitly clarified its exploratory nature (page 4, line 149).

The comment regarding the limitations inherent to the observational data used for the development of these guidelines has been carefully addressed by clearly acknowledging the absence of intervention studies and the consequent limits to clinical interpretation. These clarifications have been incorporated into the Discussion section (page 6, line 234).

Improve transparency regarding data sources and methodology.
Even for a short communication, readers should be able to understand the origin of the data that underpin the conclusions and recommendations.

We thank the reviewer for the constructive comment regarding transparency and clarity of the data sources and methodology.

We believe that these additions improve the transparency of the study design and the origin of the data, while maintaining the brevity required for this article format.

This new section can be found at page 2, line 66.

Addressing these points will substantially strengthen the scientific rigor, clarity, and interpretability of the manuscript.

We hope that we have adequately addressed the points raised and that the revisions made have strengthened the scientific rigor, clarity, and interpretability of the manuscript.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for the revised version of the manuscript. The clarity of the aims and the addition of a Methods section represent improvements. However, several important issues remain and should be addressed before publication.

First, the manuscript continues to present strong clinical recommendations that are primarily based on observational and partly unpublished data. The language throughout the manuscript should better reflect the level of evidence and avoid directive or causal interpretations that are not supported by the study design.

Second, the Methods section remains too general. Greater transparency is required regarding how the primary data were collected, measured, and analyzed, particularly for diet, cognition, physical activity, and parental BMI. Readers must be able to understand the basis on which recommendations are made.

Third, the diet–cognition association is still interpreted too strongly. Given the cross-sectional and exploratory nature of the analysis, the conclusions should be more cautious and clearly acknowledge the limits of inference.

Finally, reliance on unpublished data (Reference 7) needs clarification, as clinical recommendations should not depend heavily on non-accessible evidence.

In summary, the manuscript addresses an important topic, but further revision is necessary to better align the strength of the conclusions with the strength of the evidence and to improve methodological transparency.

I look forward to reviewing a revised version.

Author Response

Dear Authors,

We are grateful for the reviewer’s positive feedback regarding the clarity of the aims and the updated Methods section. We have now addressed the remaining issues to further improve the manuscript

Thank you for this comment.

We appreciate the concern regarding the strength of the clinical recommendations and the level of evidence supporting them. In response, we have carefully revised the manuscript to soften the language throughout and to better reflect the observational nature of the data. We have avoided directive and causal interpretations and have adjusted the relevant sections to ensure that the conclusions are appropriately aligned with the study design and the level of evidence available.

Finally, we would like to clarify that the observational study previously referred to as unpublished data has now been formally published in the journal Nutrients.

We appreciate the reviewer’s request for greater methodological transparency.

We have extensively revised the Methods section to include:

The specific tools and validated instruments used to measure diet, cognition, and physical activity.
The procedure for obtaining parental BMI.

These additions ensure that the methodology is no longer general and provides the necessary transparency regarding the study’s findings.

The new paragraph specifying this data can be found in the Methods section, specifically at page 3, line 101.

We agree with the reviewer’s comment. We acknowledge that the cross-sectional nature of our study design limits our ability to draw causal inferences regarding the impact of diet on cognition.

Following the suggestion, we have carefully revised the text to use a more cautious language. Specifically:

We have replaced definitive statements with more appropriate terms such as "associated with," "linked to," and "potentially."
We have explicitly added a sentence acknowledging the limits of inference due to the cross-sectional and exploratory nature of the data.
We have framed the clinical implications as hypotheses/potential priorities rather than established facts.

We believe these changes now provide a more balanced and scientifically rigorous interpretation.

Finally, reliance on unpublished data (Reference 7) needs clarification, as clinical recommendations should not depend heavily on non-accessible evidence.

Thank you for this important comment. We fully agree that clinical recommendations should not rely heavily on non-accessible or unpublished evidence.

In this sense, the manuscript corresponding to Reference 7, which supports a substantial part of the evidence discussed in the guidelines, has now been published in Nutrients within the same Special Issue, “Nutrition for Cognitive Health and Neuroprotection.”

Thank you for your constructive feedback. We appreciate your comments and have carefully revised the manuscript. We hope that these revisions adequately address your concerns and meet your expectations.

I look forward to reviewing a revised version.

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for submitting the revised version of your manuscript and for the detailed responses to the reviewer’s comments.

The revised manuscript shows clear improvements. In particular, the Methods section now provides greater transparency regarding the tools and procedures used to assess dietary intake, cognition, physical activity, and parental BMI. These additions help readers better understand the basis of the analyses and strengthen the methodological clarity of the study.

I also appreciate the revisions made to the language throughout the manuscript, which now more appropriately reflects the observational and cross-sectional nature of the data. The clarification that the study previously cited as unpublished data has now been formally published also improves the transparency of the evidence supporting the manuscript.

Overall, the manuscript now presents a more balanced interpretation of the findings, and the conclusions are better aligned with the level of available evidence.

Thank you for your efforts in revising the manuscript.

Kind regards,
Reviewer