PONE-D-22-30145Prevalence, risk factors, and consequences of hypothyroidism among pregnant women in the health region of Lleida: a cohort studyPLOS ONE

Dear Dr. Siscart,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR: Please revise the manuscript as suggested by the reviewer.

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Please submit your revised manuscript by Feb 09 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Mukhtiar Baig, Ph.D.

Academic Editor

PLOS ONE

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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: Yes

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: Yes

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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: The authors write in the limitation that socioeconomic status was not evaluated, however, it was part of the objectives. It should have been included.

Overall it is a well-written manuscript.

There are no concerns regarding dual publication, research ethics, or publication ethics.

Reviewer #2: Thank you for the opportunity to review the manuscript!

While the research topic is of importance to the clinicians working with pregnant women, the manuscript needs more details and some amendments to be brought to a standard format for publication.

Introduction:

- Please indicate at the end of the introduction why you have decided to conduct this study and what is the study significance and what gaps it aimed to address.

Materials and Methods

This section needs to address the following details:

- In the presented study, pregnancies were groups into low risk, medium risk, high risk and very high risk. Usually in real practice and for the sake of providing appropriate care to each group of women, pregnancies are categorised as “low risk” and “high risk”. Please indicate why you have chosen 4 gropes? Is this what is used in the real practice in the Lleida region to provide care to the women? If not, please clarify and re-group. Please modify the

Results accordingly.

- Please provide details of how you chose the criteria for adherence, how you calculated adherence score and what each score (lower/higher) means.

Results:

- “40.4-64.7% of the treated patients showed high adherence”. Why does adherence for one single group has a range? Please clarify or amend.

Table 4:

- “Duration of the pregnancy” has subgroups of “abortion”, “pre-term”, “prolonged”, and “full-term”. Please indicate the gestational age range for each item. Also, does the word “abortion” indicate both miscarriage and abortion, or does it refer to abortion only, or do you mean termination of pregnancy before 20th Weeks of gestation? They imply different meaning in clinical practice. Please clarify.

- “Newborn weight” has 3 sub-groups: underweight, macrosomia and normal weight. Please indicate the weight range for each group.

Figures 2 and 3:

- The standard format for presentation of regression results are “Adjusted OR”, “95% CI”, and “p-value”, each one sits on separate columns. Both lower and upper 95% CIs should be presented in one column for ease of reading. Please reformat the Figures.

Discussion

- “Difficulties and limitations of the study”: you have indicated that “… a lack of data for women with two gestation periods during the same year, where the data could not have been separated;”. Although not unlikely, it is uncommon that one woman gives birth to a preterm/term baby twice in one year. Do you mean both miscarriage/abortion and preterm/term pregnancies? Please clarify.

- What is the implications of the findings in practice? How can the readers use the results of the study to enhance their practice?

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6. 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.

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Reviewer #1: Yes: Dr Faiza Alam

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-22-30145R1Prevalence, risk factors, and consequences of hypothyroidism among pregnant women in the health region of Lleida: a cohort studyPLOS ONE

Dear Dr. Siscart,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 30 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Mukhtiar Baig, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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 #2: All comments have been addressed

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

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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 #2: Yes

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 #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. 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 #2: Many thanks for revising the manuscript!

Please add this description of risk groups to the text “This classification is what is used in the real practice in Lleida Region Health, on the one hand we can categorised low risk and medium risk as “low risk”. On the other hand we can categorised high risk and very high risk as “high risk”.

Please add details of adherence criteria to the text with the respective citations: “As we have observed in other studies we defined three levels of therapeutic adherence: high, for patients who took more than 80% of the drug prescribed; medium, for those who took between 50 and 80%; and low, for those who took <50%”.

The loss of pregnancy before 20th weeks can be abortion or miscarriage depending on the path. In the text, please replace “abortion” with “miscarriage/abortion”.

Figures 2 and 3: The usual format for presenting OR (CI) is up to two decimal points and for p-value is up to three decimal points. To maintain consistency, please revise Figures 2 and 3 accordingly.

Reviewer #3: The discussion section repeats most of the results already mentioned in the results section. It would be good if the discussion is re phrased to elucidate the implications of the findings from the study. Also address any discrepancies and offer insights into potential reasons for unexpected results. Suggestions for mitigation in clinical practice, counselling and future research endeavors should also be mentioned.

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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: Yes: Syeda Sadia Fatima

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Prevalence, risk factors, and consequences of hypothyroidism among pregnant women in the health region of Lleida: a cohort study

PONE-D-22-30145R2

Dear Dr. Siscart,

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,

Mukhtiar Baig, Ph.D.

Academic Editor

PLOS ONE