Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study

Jonatan Axelsson; Kristin Scott; Joakim Dillner; Christian H. Lindh; He Zhang; Lars Rylander; Anna Rignell-Hydbom

doi:10.1371/journal.pone.0236394

Peer Review History

Original SubmissionApril 24, 2020
9 Jun 2020 Decision Letter - Angela Lupattelli, Editor PONE-D-20-11886 Exposure to polychlorinated compounds and cryptorchidism; a nested case-control study PLOS ONE Dear Dr. Axelsson, 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 Jul 24 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Angela Lupattelli, PhD Academic Editor PLOS ONE Journal Requirements: 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 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 1. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0044767 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Additional Editor Comments: Dear authors, - please avoid using the terminology "statistically significant" but rather evaluate the findings of your work on the basis of the 95% CI of the observed effect estimates. - it would be informative to have a table summarizing the association meausures identified in the study. - the discussion needs some further elaboration as to why the findings do/do not align with prior research, and also in light of the comments raised by the reviewers concerning risk of misclassification of exposure, residual confounding and unmeasured confounding. [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: Partly ******** 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 authors presented a study on the association between polychlorinated compounds and cryptorchidism using linkage of a Swedish biobank and national health registers. Although the research question is not new it may be relevant to study this in a relative large sample size of 165 cases and 165 controls. My major comments to the manuscript includes 1) I would prefer to have a descriptive table on the characteristics mathced for - and although these by design should be equal in the case and control group it would be nice to see how well they fit. 2) On line 129-131 the authors stated that they decided not to include other exposures due to high correlations. The correlations reported were moderate and I would like to see the results of including additional exposures as a subanalysis or some kind of combined measure to compare with what was reported in previous studies. 3) I would prefer to see the results presented in a table in addition to the text. 4) P values from the results should be deleted since CIs gives the necessary information and p-values may be misleading since they are highly sample size dependent. 5) In the discussion add limitations: discussion of potential misclassification of exposure, outcome and matching factors and potential residual confounding. Reviewer #2: This study investigated the associations between cryptorchidism and POPs measured in first trimester maternal serum. The results showed no significant associations. However, the authors only measured only three chemicals as representatives for POP exposures. 1. Line 70. Why do the authors collect first trimester maternal serum? 2. Line 72. Although the authors believe that PCB-153 can be a representative for PCB exposures. The individual PCBs may produce effects simultaneously. 3. Line 116. Why does this paragraph only contain one sentence? ****** 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: 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.0236394.r001
Revision 1
3 Jul 2020 Author Response Response to reviewers regarding PLOS ONE Decision: Revision required [PONE-D-20-11886] - [EMID:0c61a118f2ed1618] Dear Editor, We want to thank you and the reviewers for the wise comments which here will be addressed. Our answers are shown in italics below each comment. With best regards on behalf of all co-authors, Jonatan Axelsson, MD, PhD Lund University Sweden 1. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0044767 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. -The text has been gone through, but the mentioned overlappings have not been clearly identified. Still, to highlight the similarity to the mentioned publication, a reference to the publication has been done on page 4, line 71-72. Additional Editor Comments: Dear authors, - please avoid using the terminology "statistically significant" but rather evaluate the findings of your work on the basis of the 95% CI of the observed effect estimates. -We have now deleted the part of the sentences regarding statistical significance. - it would be informative to have a table summarizing the association meausures identified in the study. -Such a table (Table 3) has now been added, and can be found on page 11. - the discussion needs some further elaboration as to why the findings do/do not align with prior research, and also in light of the comments raised by the reviewers concerning risk of misclassification of exposure, residual confounding and unmeasured confounding. -We agree that the discussion could benefit from being more precise, and now changed it to mention the review articles on the topic directly, and removed the references to original articles (page 15). We, thereafter, added the fact that DDE was associated with male reproductive disorders as a common entity in one of the review articles, and that this compound was the only one with a positive OR for the risk of cryptorchidism in our study. 5. Review Comments to the Author Reviewer #1: My major comments to the manuscript includes 1) I would prefer to have a descriptive table on the characteristics mathced for - and although these by design should be equal in the case and control group it would be nice to see how well they fit. -Such a table has now been added as Table 1, page 8 2) On line 129-131 the authors stated that they decided not to include other exposures due to high correlations. The correlations reported were moderate and I would like to see the results of including additional exposures as a subanalysis or some kind of combined measure to compare with what was reported in previous studies. -We have now added an analysis with a simultaneous inclusion of the three different exposure markers. This is mentioned in the end Methods section as a second sensitivity analysis, page 8. The results of this analysis is written on page 12 in the end of the Results section of the manuscript, as well as in the first paragraph of the Discussion. 3) I would prefer to see the results presented in a table in addition to the text. -Such a table (Table 3) of the main analysis has now been added, and can be found on page 11. 4) P values from the results should be deleted since CIs gives the necessary information and p-values may be misleading since they are highly sample size dependent. -The p values have now been deleted from the manuscript. 5) In the discussion add limitations: discussion of potential misclassification of exposure, outcome and matching factors and potential residual confounding. -We have now added a discussion about a possible misclassification of the outcome (page 13). After this discussion we changed the formulation of the beginning of the next paragraph (line 213), and also added an additional reference to the mentioning of the study by Damgaard et al for clarification (reference 28). We have thereafter also added a discussion of possible misclassification of the exposure, and of the matching factors. It is hard to evaluate the risk of possible residual confounding since few environmental risk factors, are known. This has also been added to the discussion. Reviewer #2: This study investigated the associations between cryptorchidism and POPs measured in first trimester maternal serum. The results showed no significant associations. However, the authors only measured only three chemicals as representatives for POP exposures. -We have now added some reasoning around the possible relevance also for other compounds not measured (page 14, line 228-). 1. Line 70. Why do the authors collect first trimester maternal serum? - The samples available from the biobank were taken in early pregnancy when the screening for rubella is done in Sweden. Still, we believe that these levels are representative due to correlations reported between POP levels in first trimester and levels in cord blood. This is now mentioned in the Discussion, page 13 (line 195-197). 2. Line 72. Although the authors believe that PCB-153 can be a representative for PCB exposures. The individual PCBs may produce effects simultaneously. -It is true that individual PCBs may produce effects simultaneously. Still, at least two studies reported that PCB-153 was a good marker for the sum of PCBs in serum. We now added one of these references to the discussion on page 14, line 227 (reference 17). We have also added the correlation between PCB-153 and the possibly antiandrogenic PCB-138 on line 228-232. 3. Line 116. Why does this paragraph only contain one sentence? -This sentence was separated from the rest of the paragraph to make it more easily discernible, but has now been moved as a final sentence to the paragraph above, since it is still related to the determination of the compounds. As an additional change during the revision process we have limited the number of decimals in the ranges of the levels of the POPs in the different quartiles in Table 2. https://doi.org/10.1371/journal.pone.0236394.r002
8 Jul 2020 Decision Letter - Angela Lupattelli, Editor Exposure to polychlorinated compounds and cryptorchidism; a nested case-control study PONE-D-20-11886R1 Dear Dr. Axelsson, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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 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, Angela Lupattelli, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0236394.r003
Formally Accepted
15 Jul 2020 Acceptance Letter - Angela Lupattelli, Editor PONE-D-20-11886R1 Exposure to polychlorinated compounds and cryptorchidism; a nested case-control study Dear Dr. Axelsson: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Angela Lupattelli Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0236394.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 .