PONE-D-23-40210The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study - A controlled intervention study: protocol paperPLOS ONE

Dear Dr. Winckler,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

Reviewer #2: No

Reviewer #3: 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

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for presenting your protocol.

I have only one suggestion: Primary outcomes should include the rates of preterm birth (below 37 weeks and below 34 weeks), because this is a more clinically useful parameter, and should improve your work acceptance.

Reviewer #2: A two-arm controlled study is being proposed where the aim is to determine whether periodontal treatment during pregnancy can reduce systemic inflammation and lower risk of complications during pregnancy.

Minor revisions:

1- Abstract: “The aim of this study is to determine whether periodontal treatment during pregnancy can reduce systemic inflammation and lower risk of complications during pregnancy and fetal growth.” The “and fetal growth” phrase in this sentence is confusing.

2- In the abstract, clarify if the study will be randomized or not.

3- The standard statistical term for average is mean.

4- Line 226: Power calculation. Indicate the statistical testing method used to estimate the power in the scenarios.

5- Line 240: List the confounders.

6- Line 240: Describe the statistical methods that will be applied to analyze changes in hormonal and inflammatory markers.

7- Procedure for testing an interaction effect: If the interaction effect is significant, provide an interpretation of the results, but do not test main effects because the tests for main effects are uninteresting in light of significant interactions. If interaction effects are non-significant, drop the interaction effects from the model and test the main effects. Determining which results to present when testing interactions is often a multi-step process.

8- Identify the software that will be used for statistical analysis.

Reviewer #3: In the manuscript entitled: " The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study - A controlled intervention study: protocol paper" the authors aimed to assess whether periodontal treatment during pregnancy can reduce systemic inflammation and lower risk of complications during pregnancy and fetal growth.

The authors concluded that Furthermore, the results will be communicated via social media, presented at academic meetings, and shared with participating communities as well as with national and international policymaking bodies. The REDCap platform, which will be used to collect demographic data, measures from the periodontal examinations, and data from the qualitative questionnaires, is a secure, web-based application designed to enable responses to be automatically uploaded into safe data storage to maximize data security.

Major comments:

In general, the idea and innovation of this study regards the analysis of oral and periodontal health in pregnancy is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design.

The study was well conducted by the authors; However, there are some concerns to revise that are described below.

The introduction section resumes the existing knowledge regarding the important factor linked with the impact mediators involved together oral health and with periodontitis.

However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the role of mediators (NT-PRO-BNP and TGF beta 1) in periodontitis and related recessions by adding as a references these article, before any further assessment of the manuscript: 1) DOI: doi: 10.1002/JPER.23-0063. PMID: 37433155; 2) DOI: 10.1177/1721727X1301100217

The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample.

Please better state the results obtained in the abstract.

The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution that could improve the quality of life in periodontitis patients which undergo pregnancy. The conclusion should reinforce in light of the discussions.

In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for publication in this journal and requests a revision before a futher re-evaluation of the manuscript.

Minor Comments:

Abstract:

-Better formulate the abstract section by better describing the aim of the study

Introduction:

-Please refer to major comments

Discussion

-Please add a specific sentence that clarifies the results obtained in the first part of the discussion

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study - A controlled intervention study: protocol paper

PONE-D-23-40210R1

Dear Dr. Winckler,

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,

Gaetano Isola, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have well addressed all issuea raised by the reviewers

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: Yes

Reviewer #3: Yes

**********

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 #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: All comments have been adequately addressed.

Reviewer #3: In this revised version of the manuscript, the authors have well addressed all issues raised by the reviewer. The manuscript can be accepted for publication.

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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 #2: No

Reviewer #3: No

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