The incidence of chronic pain following Cesarean section and associated risk factors: A cohort of women followed up for three months

Natália Carvalho Borges; José Miguel de Deus; Rafael Alves Guimarães; Délio Marques Conde; Maria Márcia Bachion; Louise Amália de Moura; Lilian Varanda Pereira

doi:10.1371/journal.pone.0238634

Peer Review History

Original SubmissionMay 14, 2020
17 Jun 2020 Decision Letter - Ehab Farag, Editor PONE-D-20-14430 The incidence of chronic pain following Cesarean section and associated risk factors: a cohort of women followed up for three months PLOS ONE Dear Dr. To: Natalia Carvalho Borges 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. ============================== I would appreciate if you respond carefully to the reviewers' comments in your reply. Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact. ============================== Please submit your revised manuscript by Aug 01 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, Ehab Farag, MD FRCA FASA 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 2. 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 (if provided): I would appreciate if you respond carefully to the reviewers' comments in your reply. [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: Yes 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: Line 81 please add "elective" before Cesarean Is there a role of prior C Section on chronic pain? Please elaborate on the incidence of chronic pain in primary versus repeat C section. Manuscript well written and comprehensive Reviewer #2: I congratulate the authors in doing this prospective study. This topic is very important and well described. 1. What analgesics did patients receive in post operative period other than dipyrone? 2. Do you allow partner's presence during cesarean section to reduce anxiety? 3. Do patients receive analgesic when they were in pain after 7 days of surgery? 4. Can you provide the severity of pain at 90 days? 5. Did patients demand analgesic at 60 and 90 days? 6. Any H/O drug abuse in the past for any of the patients? 7. Can you include the surgeon variable? (eg- is there one or two particular surgeons whose patients had less pain or more CPSP? ****** 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: Yes: SABRY AYAD MD MBA FASA Reviewer #2: Yes: JAGAN DEVARAJAN [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.0238634.r001
Revision 1
30 Jul 2020 Author Response Reviewer 1 Comment: Line 81 please add "elective" before Cesarean The reviewer’s suggestion implies that the description of the study population was not clear; therefore, we decided that the text should be improved. The present study sample described in the manuscript was indeed made up of women who had been submitted to an elective Cesarean section, i.e. prior to the onset of labor and rupture of the membranes [1,2]. Nevertheless, the main study in which this study was nested included all the women admitted for a Cesarean section (n=1,122) irrespective of whether or not the procedure was elective. For this reason, we decided not to include the term “elective” before “Cesarean section” in that specific segment, as suggested by the reviewer, since this would lead to the interpretation that only women submitted to an elective Cesarean section had participated in the larger main study, which was not the case. Therefore, to improve our description of the study population, we have rewritten the relevant segment of the Methods section (page 4, lines 80-85), as follows: “For the larger main study, 1,122 women who were admitted to hospital for a Cesarean section were recruited. The present study included only those who underwent an elective Cesarean section and who did not meet the following exclusion criteria: age <20 years, presence of pain in the pelvic region that preceded pregnancy, women who had requested that tubal ligation be performed during the Cesarean section, women who had difficulty in communicating verbally, and those in continuous use of opioids.” Comment: Is there a role of prior C Section on chronic pain? Please elaborate on the incidence of chronic pain in primary versus repeat C section There is some evidence that previous surgeries may play a role in the chronification of postoperative pain [3–6]. This may occur due to repeated exposure to postoperative pain treated with opioids, resulting in central sensitization and hyperalgesia [5] and/or to the increased risk of nerve entrapment caused by the increase in fibroses at repeat surgeries [6]. Consequently, we analyzed the effect of exposure to a prior Cesarean section and the occurrence of chronic postoperative pain. These results are shown in Table 2 (page 12). In agreement with other studies with similar populations [7–13], there was no statistically significant difference between the incidence of chronic postoperative pain in women who had been submitted to a previous C-section and those who were undergoing the procedure for the first time. Reviewer 2 Comment: What analgesics did patients receive in postoperative period other than dipyrone? Thank you for this question. Data regarding the medication received for pain relief were collected postoperatively for all the women in the cohort (n=620) while they were still in hospital. We have now added further information on this subject in the Results section (page 10, lines 179-184), as follows, and have added an extra table (S1 Table) in the Supporting Information section. “Of the 620 women monitored after surgery, all received some type of medication for pain relief while in hospital. As shown in S1 Table, almost all (99.7%) were given simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) (93.3%) during this period. Of the simple analgesics, dipyrone was the most commonly administered medication (99.2%), while, of the NSAIDs, diclofenac sodium was the most common (99.5%). Only five women (0.8%) were given an opioid analgesic during this period”. Comment: Do you allow partner's presence during cesarean section to reduce anxiety? Not all of the women were able to have an accompanying person in the operating room, since permission for a companion to be present in the hospital where data collection was performed was dependent on authorization from the attending surgeon. In this study, data are not available on this factor since this information was not collected in a standardized manner. Comment: Do patients receive analgesic when they were in pain after 7 days of surgery? Comment: Did patients demand analgesic at 60 and 90 days? Yes, some of the women were in use of pain relief medication during follow-up. The reviewer’s question made us reconsider how this information was provided in the manuscript and we decided to add a paragraph in the Results section and include some supplementary tables (S2-S5 Tables) regarding the use of pain medication during follow-up. Since information was included on the use of medication at all evaluation moments during follow-up, we deemed it relevant to also present related data in the flowchart of the cohort. Therefore, we have changed the flowchart to add the number of women evaluated at 30 and 60 days following surgery (Fig 1). The following paragraph was included in the manuscript (page 10, lines 185-192) and refers to the additional tables: “Following discharge from hospital, 95.8%, 36.0%, 15.5% and 17.0% of the women with surgery-related pain used some form of pain relief medication on the 7th, 30th, 60th and 90th day after the Cesarean section, respectively. Of the women who used simple analgesics, dipyrone was the drug of choice at all the evaluation moments (7th day = 95.9%; 30th day = 87.2%; 60th day = 91.7% and 90th day = 90.9%). Of those who used an NSAID, diclofenac sodium was the most commonly used drug throughout follow-up (7th day = 97.9%; 30th day = 92.3%; 60th day = 90.0% and 90th day = 71.4%). None of the participants used an opioid following discharge from hospital (S2-S5 Tables)”. Comment: Can you provide these severity of pain at 90 days? Yes, the women reporting pain on the 90th day following surgery were asked about the intensity of this symptom, particularly when the pain was most intense. We have added the following segment to the Results section (page 10, lines 194-196). “When the women with CPSP (n=118) were asked about the intensity of pain at the moment when this symptom was most intense, 16.1%, 47.5% and 36.4% reported mild, moderate and severe pain, respectively. The mean intensity of pain was 5.7 (±2.3 SD)”. Comment: Any H/O drug abuse in the past for any of the patients? In relation to drug abuse, prior to surgery the patients were asked about their use of opioids, alcohol and tobacco. All stated that they did not use opioids (an exclusion criterion). Data on alcohol consumption and smoking are shown in the tables. Regarding opioid use, we have now included the following phrase in the manuscript as part of the exclusion criteria in the Methods section (page 4, line 85): “and those in continuous use of opioids.”. Comment: Can you include the surgeon variable? (e.g. is there one or two particular surgeons whose patients had less pain or more CPSP? At this institute, six different surgeons perform Cesarean sections. In the present study, it was not possible to include data on the variable “surgeon” since this information was not collected in a standardized manner. REFERENCES 1. World Health Organization. (‎2018)‎. WHO recommendation: elective C-sections hould not be routinely recommended to women living with HIV: policy brief. World Health Organization. https://apps.who.int/iris/handle/10665/272454. 2. International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1 – a meta-analysis of 15 prospective cohort studies. N Engl J Med. 1999;340:977–987. doi:10.1056/NEJM199904013401301 3. Brandsborg B, Nikolajsen L, Hansen CT, Kehlet H, Jensen TS. Risk factors for chronic pain after hysterectomy: A Nationwide questionnaire and database study. Anesthesiology. 2007;106:1003–1012. doi: 10.1097/01.anes.0000265161.39932.e8 4. Rivat C, Laboureyras E, Laulin J-P, Le Roy C, Richebé P, Simonnet G. Non-nociceptive environmental stress induces hyperalgesia, not Analgesia, in pain and opioid-experienced rats. Neuropsychopharmacology. 2007;32:2217–28. doi:10.1038/sj.npp.1301340 5. Rivat C, Ballantyne J. The dark side of opioids in pain management: basic science explains clinical observation. Pain Reports. 2016;1:e570. doi: 10.1097/PR9.0000000000000570 6. Loos MJ, Scheltinga MR, Mulders LG, Roumen RM. The Pfannenstiel Incision as a Source of Chronic Pain. Obstet Gynecol. 2008;111:839–846. doi:10.1097/AOG.0b013e31816a4efa 7. Nikolajsen L, Sorensen HC, Jensen TS, Kehlet H. Chronic pain following Caesarean section. Acta Anaesthesiol Scand. 2004;48: 111–116. doi:10.1111/j.1399-6576.2004.00271.x 8. Sng BL, Sia ATH, Quek K, Woo D, Lim Y. Incidence and Risk Factors for Chronic Pain after Caesarean Section under Spinal Anaesthesia. Anaesth Intensive Care. 2009;37: 748–52. doi:10.1177/0310057X0903700513 9. Kainu JP, Halmesmaki E, Korttila KT, Sarvela PJ. Persistent pain after cesarean delivery and vaginal delivery: A prospective cohort study. Anesth Analg. 2016;123: 1535–1545. doi:10.1213/ANE.0000000000001619 10. Liu TT, Raju A, Boesel T, Cyna AM, Tan SGM. Chronic pain after caesarean delivery: An Australian cohort. Anaesth Intensive Care. 2013;41: 496–500. doi:10.1177/0310057x1304100410 11. Nardi N, Campillo-Gimenez B, Pong S, Branchu P, Ecoffey C, Wodey E. Douleurs chroniques après césarienne: Impact et facteurs de risque associés. Ann Fr Anesth Reanim. 2013;32: 772–778. doi:10.1016/j.annfar.2013.08.007 12. Moriyama K, Ohashi Y, Motoyasu A, Ando T, Moriyama K, Yorozu T. Intrathecal administration of morphine decreases persistent pain after cesarean section: A prospective observational study. PLoS One. 2016;11: 1–13. doi:10.1371/journal.pone.0155114 13. Brotons MJS, Echevarria M, Turmo M, Almeida C. Chronic Pain and Predictive Factors in the C-Section Surgery. J Anesth Clin Care. 2016;3: 1–6. doi:10.24966/acc-8879/100015 Attachments Attachment Submitted filename: Response to Reviewers.pdf https://doi.org/10.1371/journal.pone.0238634.r002
21 Aug 2020 Decision Letter - Ehab Farag, Editor The incidence of chronic pain following Cesarean section and associated risk factors: a cohort of women followed up for three months PONE-D-20-14430R1 Dear Dr. Natalia Carvalho Borges 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, Ehab Farag, MD FRCA FASA Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0238634.r003
Formally Accepted
27 Aug 2020 Acceptance Letter - Ehab Farag, Editor PONE-D-20-14430R1 The incidence of chronic pain following Cesarean section and associated risk factors: a cohort of women followed up for three months Dear Dr. Borges: 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. Ehab Farag Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0238634.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 .