Pregnancy outcomes in women with vitiligo: A Taiwanese nationwide cohort study

Chih-Tsung Hung; Hsin-Hui Huang; Chun-Kai Wang; Chi-Hsiang Chung; Chang-Huei Tsao; Wu-Chien Chien; Wei-Ming Wang

doi:10.1371/journal.pone.0248651

Peer Review History

Original SubmissionDecember 29, 2020
3 Feb 2021 Decision Letter - Christy Pu, Editor PONE-D-20-40830 Pregnancy outcomes in women with vitiligo: a Taiwan nationwide cohort study PLOS ONE Dear Dr. Hung, 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 Mar 19 2021 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. 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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: [The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.] Please include your amended statements within your cover letter; we will change the online submission form on your behalf. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions 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: 1. The study of the relations between pregnant outcomes and vitiligo is quite rare, this research points out some unknown features by applying large scale research database. 2. The Taiwan National Health Insurance (NHI) and the National Health Insurance Research Database (NHIRD) should be different. Are there any references indicating the coverage rate (>99% in the text) and the reimbursement system of NHI? Further, how it works between the NHI and NHIRD? Third, the abbreviation of NHIRD should be used when it first appeared in the manuscript. 3. As mentioned in the study limitation section, the extend and severity of the vitiligo is difficult to be defined, therefore, the treatment of choice remained controversy. Topical agents have longstanding been used as the first line therapy, why only systemic treatments were regarded as preconception treatment? Consequently, should the 800 cases who were assigned as “without treatment” be “real non treatment” or “topical treatment”? Since those cases without treatment also remained controversy, the term used in the table 3 should be revised, and the conclusion also should be reconsidered accordingly. 4. As for the comorbid diseases, the SLE/Sjogren’s syndrome/RA were excluded for the enrollment in the beginning, so how to explain why those diseases still existed in the abortion group of vitiligo patients? Furthermore, immunosuppressive agents such as methotrexate and azathioprine are not common as the systemic medications for vitiligo prescribed by dermatologists, is there any explanation? [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.0248651.r001
Revision 1
15 Feb 2021 Author Response 1. The study of the relations between pregnant outcomes and vitiligo is quite rare, this research points out some unknown features by applying large scale research database. Response: Thanks for your kind comment. The purpose of our study is to emphasize the importance of vitiligo in pregnant women. Out of personal discussion, most obstetricians would check whether pregnant patients were previously diagnosed as SLE or Sjögren’s syndrome, but vitiligo which is also an autoimmune disease seldom drew their attention. Besides, our study also revealed the importance of disease control with systemic treatment to reduce the risk of miscarriage. 2. The Taiwan National Health Insurance (NHI) and the National Health Insurance Research Database (NHIRD) should be different. Are there any references indicating the coverage rate (>99% in the text) and the reimbursement system of NHI? Further, how it works between the NHI and NHIRD? Third, the abbreviation of NHIRD should be used when it first appeared in the manuscript. Response: Thanks for your kind comment and reminder. Taiwan National Health Insurance (NHI) is a single-payer compulsory social insurance. This system promises equal access to healthcare for all citizens, and the coverage had reached 99% [1]. NHIRD, the large computerized databases, derived from the National Health Insurance Administration (the former Bureau of National Health Insurance, BNHI), Ministry of Health and Welfare (the former Department of Health, DOH), Taiwan and maintained by the National Health Research Institutes, Taiwan, are provided to scientists in Taiwan for research purposes. The data in NHIRD is fully anonymized linked information, including outpatient care, inpatient care, emergency care, treatment procedures, and prescription drugs. 3. As mentioned in the study limitation section, the extend and severity of the vitiligo is difficult to be defined, therefore, the treatment of choice remained controversy. Topical agents have longstanding been used as the first line therapy, why only systemic treatments were regarded as preconception treatment? Consequently, should the 800 cases who were assigned as “without treatment” be “real non treatment” or “topical treatment”? Since those cases without treatment also remained controversy, the term used in the table 3 should be revised, and the conclusion also should be reconsidered accordingly. Response: Thanks for your kind reminder. As your comment, topical agents have longstanding been used as the first line therapy. In this study, we want to know if the systemic treatment before pregnancy decreases the risk of abortion or not, and we revised our article accordingly, including manuscript and tables. 4. As for the comorbid diseases, the SLE/Sjogren’s syndrome/RA were excluded for the enrollment in the beginning, so how to explain why those diseases still existed in the abortion group of vitiligo patients? Furthermore, immunosuppressive agents such as methotrexate and azathioprine are not common as the systemic medications for vitiligo prescribed by dermatologists, is there any explanation? Response: Thanks for your kind comment. This is a retrospective cohort study ranging from January 1st, 2000 to December 31st, 2015. SLE/Sjogren’s syndrome/RA were excluded for the enrollment in the beginning, and we rechecked our enrolled data that no one was diagnosed of SLE/Sjogren’s syndrome/RA before their first pregnancy. We kept following the medical records after their first pregnancy and found the increased risk of SLE/Sjogren’s syndrome/RA in patients with vitiligo who experienced abortion. Besides, steroid phobia is a common problem in my country. Some patients rejected any treatment containing steroid, including topical and oral agents. At that time, we will arrange phototherapy and/or prescribe topical calcineurin inhibitors and/or oral immunosuppressive agents, such as methotrexate and azathioprine, to control their vitiligo disease activity. Reference 1. Wu T-Y, Majeed A, Kuo KN. An overview of the healthcare system in Taiwan. London journal of primary care. 2010;3(2):115-9. Attachments Attachment Submitted filename: Reviewer opinion and response.doc https://doi.org/10.1371/journal.pone.0248651.r002
23 Feb 2021 Decision Letter - Christy Pu, Editor PONE-D-20-40830R1 Pregnancy outcomes in women with vitiligo: a Taiwanese nationwide cohort study PLOS ONE Dear Dr. Hung, 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 Apr 09 2021 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, Christy Pu 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. Additional Editor Comments: 1. Please remove results from Discussion. 2. Odds ratios among different studies (or models) should never be compared in terms of magnitudes. This is a common mistake. Please remove all comparisons and rephrase all relevant discussions. 3. In the Limitation section, please discuss briefly direction of bias and how they may affect your conclusion. [Note: HTML markup is below. Please do not edit.] [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.0248651.r003
Revision 2
26 Feb 2021 Author Response 1. Please remove results from Discussion. Response: Thanks for your kind comment. The results were removed from discussion in the revised article accordingly. 2. Odds ratios among different studies (or models) should never be compared in terms of magnitudes. This is a common mistake. Please remove all comparisons and rephrase all relevant discussions. Response: Thanks for your kind comment and reminder. We revised and rephrased our article accordingly. 3. In the Limitation section, please discuss briefly direction of bias and how they may affect your conclusion. Response: Thanks for your kind comment and reminder. We took your recommendation and revised our article accordingly. Attachments Attachment Submitted filename: Reviewer opinion and response.doc https://doi.org/10.1371/journal.pone.0248651.r004
3 Mar 2021 Decision Letter - Christy Pu, Editor Pregnancy outcomes in women with vitiligo: a Taiwanese nationwide cohort study PONE-D-20-40830R2 Dear Dr. Hung, 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, Christy Pu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0248651.r005
Formally Accepted
12 Mar 2021 Acceptance Letter - Christy Pu, Editor PONE-D-20-40830R2 Pregnancy outcomes in women with vitiligo: a Taiwanese nationwide cohort study Dear Dr. Wang: 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. Christy Pu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0248651.r006

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