Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors

Eilidh M. Wood; Kylie K. Hornaday; Matthew Newton; Melinda Wang; Stephen L. Wood; Donna M. Slater

doi:10.1371/journal.pone.0315484

Peer Review History

Original SubmissionNovember 28, 2024
Decision Letter - Godwin Anywar, Editor Dear Dr. Slater, 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 Jan 24 2025 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. 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, Godwin Upoki Anywar, BSc, Msc, PhD Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. 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 https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf [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? 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 Reviewer #1: No Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: Well-written article with logically conducted data analysis. Unfortunately, the review of available current literature was not conducted correctly 1. the consent of the bioethics committee does not have a date of issue (day, month, year) 2. material and methods should provide the main metabolites that were analyzed (lipoxins, 5,8,12,15 HETE, leukotriene, thromboxane, protectins, maresins, resovins) or if only PG and their sunny please do not mislead in the description (also abstract) 3. the supplement may contain results indicating no differences between the remaining metabolites 4. the discussion should be rearranged and discussed to the already described fresh/new articles. Currently, out of 67 publications, only 10 items from the last 5 years. There are several hundred of them in the PubMed database alone 5. It is suggested to include new reports from the last 10 years 6. old literature should be removed and replaced 2-5, 7-9, 11-13, 21, 24, 27-35, 39-56, 58-59, 62-65 7. the summary right after the discussion without a description of the discussion line 281-282 is incomprehensible 8. the conclusion refers to 20 metabolites but it is not clear from the article which ones? it should be adjusted best regards Reviewer #2: This study investigates urinary prostaglandin metabolites as potential biomarkers for labor, with a focus on both term and preterm conditions. The research uses ELISA and mass-spectrometry to evaluate changes in prostaglandin levels across different gestational stages and labor conditions. I would suggest some revisions as follows: 1)The threatened preterm labor (TPTL) group includes both preterm labor and preterm premature rupture of membranes (PPROM) cases. This might confound the results, as these conditions could involve distinct pathways. pls mention this in discussion limitations 2)Figures are informative but could benefit from improved clarity (e.g., larger font sizes for axes). 3)Some terms (e.g., "threatened preterm labor") should be clearly defined early in the manuscript for consistency and clarity. 4)If possible, reanalyze data by separating TPTL cases into labor-related and PPROM-related events to clarify molecular differences. ****** 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: No ******** [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. https://doi.org/10.1371/journal.pone.0315484.r001
Revision 1
16 Jan 2025 Author Response Thank you for giving us the opportunity to submit a revised draft of the manuscript “Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors” for publication in PLOS ONE. We appreciate the time and effort that the reviewers have given to providing valuable feedback on our manuscript. Please see below for a point-by-point response to the reviewer’s comments and suggestions.. Reviewer 1: Comment 1: the consent of the bioethics committee does not have a date of issue (day, month, year) Response: We have included the date of issue of institutional ethics on line 99 (page 5). Comment 2: material and methods should provide the main metabolites that were analyzed (lipoxins, 5,8,12,15 HETE, leukotriene, thromboxane, protectins, maresins, resovins) or if only PG and their sunny please do not mislead in the description (also abstract) Response: We have included a description of the major classes of eicosanoids measured by mass spectrometry in the materials and methods section, lines 176-184, page 9. Details of all the eicosanoids measured are also included in S3 Appendix. Comment 3: the supplement may contain results indicating no differences between the remaining metabolites Response: All the raw data is present. We have not performed statistics on the mass spectrometry data in the supplemental file (Appendix 1) due to the small sample size for the discovery analysis combined with some eicosanoids that were below the limit of detection. We have included a statement of this in the statistical analysis section of the methods, lines 210-213, page 10. Comments 4-6: the discussion should be rearranged and discussed to the already described fresh/new articles. Currently, out of 67 publications, only 10 items from the last 5 years. There are several hundred of them in the PubMed database alone. It is suggested to include new reports from the last 10 years. Old literature should be removed and replaced 2-5, 7-9, 11-13, 21, 24, 27-35, 39-56, 58-59, 62-65 Response: We have now included more up to date sources where possible, however in some cases the references cited are the most recent available primary articles on the subject, despite being published more than 20 years ago. New references are highlighted in yellow. Justifications for keeping select older references are detailed below. - We have kept reference 9 (Karim et al., 1968) as it is the first report of the use of prostaglandins for induction of labour and provides important historical context surrounding the clinical use of prostaglandins in labour. However, we have also included two recent meta-analyses on the use of prostaglandins for labour induction. - Reference 24 (Boeniger et al., 1993) is included in reference to a formula that was developed in said publication in 1993. We have also included a more recent citation that uses this formula for a similar purpose (MacPherson et al., 2018). Comment 7: the summary right after the discussion without a description of the discussion line 281-282 is incomprehensible Response: We have removed the “Summary” subheading from the discussion section (line 299 page 17). Comment 8: the conclusion refers to 20 metabolites but it is not clear from the article which ones? it should be adjusted Response: We have removed the reference to the 20 eicosanoids from the conclusion section to avoid confusion and have included a new table (Table 4 page 16) detailing the 20 eicosanoids that were detectable in at least half of the discovery cohort samples. Reviewer 2: Comment 1: The threatened preterm labor (TPTL) group includes both preterm labor and preterm premature rupture of membranes (PPROM) cases. This might confound the results, as these conditions could involve distinct pathways. pls mention this in discussion limitations Response: Please see highlighted limitations section lines 387-393 (page 21). Comment 2: Figures are informative but could benefit from improved clarity (e.g., larger font sizes for axes). Response: Thank you for the suggestion. We have increased the font sizes of all the axes by at least 2 points. Comment 3: Some terms (e.g., "threatened preterm labor") should be clearly defined early in the manuscript for consistency and clarity. Response: We have expanded the description of threatened preterm labour in the introduction (lines 65-66, page 3) and have made the definition of threatened preterm labour more explicit in the methods section (lines 121-125, page 6). Comment 4: If possible, reanalyze data by separating TPTL cases into labor-related and PPROM-related events to clarify molecular differences. Response: We recognize this is a limitation of the present study, however it is not possible to analyze the TPTL cases separately by presence/absence of PPROM as there are only n=4 cases of PPROM within these groups. We have included an additional, separate analysis with the n=4 PPROM cases excluded in a new supplemental file (S4 Appendix) and have added a description of this analysis to the results (lines 234-238, page 12). Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0315484.r002
Decision Letter - Godwin Anywar, Editor Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors PONE-D-24-52502R1 Dear Dr. Wood, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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 help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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. Kind regards, Godwin Upoki Anywar, BSc, Msc, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #3: All comments have been addressed Reviewer #4: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #3: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #3: Yes Reviewer #4: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #3: Yes Reviewer #4: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #3: Yes Reviewer #4: Yes ****** Reviewer #3: The revised version of the manuscript is improved and the authors made the appropriate changes suggested by the reviewers and replied properly to the comments and concerns. There is a typo mistake: In Table 4 change Arachadonic acid to Arachidonic acid Reviewer #4: Almost comments have been addressed. There are some minor comments. 1) Line 511-513: Ref34 does not include the publication year or page number. 2) S3 Appendix: The statement "LOD = limit of detection" at the bottom of the table is unnecessary. ****** 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 #3: Yes: Paola Patrignani Reviewer #4: No ******** https://doi.org/10.1371/journal.pone.0315484.r003
Formally Accepted
Acceptance Letter - Godwin Anywar, Editor PONE-D-24-52502R1 PLOS ONE Dear Dr. Slater, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Godwin Upoki Anywar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315484.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .