PONE-D-19-22011

Associations between symptoms of sleep-disordered breathing and maternal sleep patterns with late stillbirth: findings from an individual participant data meta-analysis.

PLOS ONE

Dear Mrs Cronin,

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.

We would appreciate receiving your revised manuscript by Feb 19 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Claudio Liguori

Academic Editor

PLOS ONE

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2.  Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

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

Mrs Cronin reports grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), grants from Sir John Logan Campbell Medical Trust, during the conduct of the study;

Ms. Wilson reports grants from 2016 TransTasman Red Nose/Curekids (6601);

Dr. Gordon reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Early Career Fellowship #1089898,  outside the submitted work;

Dr. Li reports grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study;

Dr. Culling has nothing to disclose;

Associate Professor Raynes-Greenow reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Career Development Fellowship #1087062, outside the submitted work;

Professor Heazell reports grants from Action Medical Research, during the conduct of the study; grants from Tommy's, grants from NIHR, outside the submitted work;

Dr. Stacey reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., during the conduct of the study;

Professor Askie has nothing to disclose;

Professor Mitchell reports grants from Cure Kids (Grant 3537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study; other from Cure Kids, outside the submitted work;

Associate Professor Thompson reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study;

Professor McCowan reports grants from Cure Kids (537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357);  Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study.

Associate Professor O'Brien reports grants from American Sleep Medicine Foundation, grants from ResMed, outside the submitted work;

We note that you received funding from a commercial source: ResMed

Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc.

Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Additional Editor Comments:

Only some minor changes have been requested by the Reviewers; please modify the manuscript as requested.

[Note: HTML markup is below. Please do not edit.]

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: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: No

Reviewer #2: Yes

**********

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

**********

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 aim of this work is to find the relationship of symptom of SDB and late stillbirth from previously done case-control studies that is available and pool them together using statistical technique. The point that this paper is a successful collaboration between large teams around the globe combining with a robust individual patient-level data analysis technique is interesting. I congratulate the authors for their efforts.

Overall I find the manuscript to be of good quality, however some minor revision points may need to be done:

1. Study selection process report need to be more transparent, i.e. the authors should describe number of study that were excluded (fig. 1 may need to be revised) how many duplicates were there?, why 124 studies did not meet the eligibility criteria? There should be more detail on the number and reason of studies that were excluded, to provided that the author has established all available evidences to support the meta-analysis. Also, for one study that is not participating, is there any difference in characteristic of that particular study compared to participating studies? (The author may need to describe about this in the result)

2. Case control studies were prone to recall bias and combining case-control in meta-analysis can still be susceptible to this. I wonder if there any other supporting evidences from cohort study? If there is not the author should specifically mention about the result of the assessment of quality of the evidence in the result, and emphasis on the possibility of bias upon making conclusion, which may need a large pregnancy cohort to be done.

Again, I sincerely admire the authors' efforts into the collaborating process.

Reviewer #2: Comments to the Author

-How the duration of overnight sleep was evaluated? Did you use a standardized sleep log?

-How did you evaluated the sleep position (supine and not supine)? Is this data only self-reported? Or did you use some instruments to evaluate it? If only self-reported, it can probably be inaccurate because you can’t know the real position throughout the night. Can you specify it?

-You suggest that a reduction in the odds of late stillbirth for women who reported restless sleep during the last month may be is due to maternal body movement facilitating maternal-fetal blood flow, potentially abating adverse fetal effects of aortocaval compression. Considering that the supine position is associated with an increase in aortocaval compression, have you evaluated interactions between restless sleep and sleep position to understand if the reduced risk of late stillbirth in these cases can be related to the position?

-You report that the combined effect of supine going-to-sleep position and habitual snoring resulted in a reduced odds of late stillbirth in the multivariable model and you explain this result assuming that snoring can cause arousal that can cause a change of position from supine to lateral. It would be interesting to test this hypothesis with an objective assessment of the position.

-You report that getting up to use the toilet in the night is associated with a reduced risk of late stillbirth, suggesting that maternal body movement on the night may mitigate the effects of a hypoxic event on the fetus. Considering that getting up to use the toilet in the night can be also a clinical manifestation of SBD, have you analyzed interactions between the use of the toilet in the night and Berlin Questionnaire (excluding BMI)?

-Non using objective measures (polysomnography) for SBD’s evaluation may be a limitation as you specified. Didn’t you evaluate the possibility to assess the polysomography, if not possibile in all the women, in some of them such as patients with positive Berlin Questionnaire (excluding BMI), in patients with restless sleep and in patients getting up to use the toilet?

**********

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.

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: No

Reviewer #2: Yes: Dott.ssa Francesca Furia

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Associations between symptoms of sleep-disordered breathing and maternal sleep patterns with late stillbirth: findings from an individual participant data meta-analysis.

PONE-D-19-22011R1

Dear Dr. Cronin,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Claudio Liguori

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 #2: All comments have been addressed

**********

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

**********

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

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 #2: 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

**********

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: I congratulate the authors for their work. I find that the manuscript is well written, well analizyzed and of good quality.

**********

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: Yes: Francesca Furia