{"paper_id":"4d598eb5-4251-4fdc-9deb-2bf7adf2e271","body_text":"SAFEHERE-KM: A prospective multicenter registry-based observational study protocol on the safety of postpartum herbal medicine in Korean medicine clinics | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol SAFEHERE-KM: A prospective multicenter registry-based observational study protocol on the safety of postpartum herbal medicine in Korean medicine clinics Anna Kim, Eunbyul Cho, Young-Eun Kim, Su-Min Seo, Sungha Kim, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6911139/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Postpartum conditions significantly affect maternal and infant health. In South Korea, herbal medicine (HM) is commonly used for postpartum care in Korean Medicine (KM), but safety data on it remain limited. This study outlines a multicenter KM clinic registry designed to investigate treatment information and adverse events (AEs) in patients taking postpartum HM. Our aim is to build evidence for evaluating the safety of HM. Methods : This prospective observational registry will enroll 1,000 postpartum patients from 15 KM clinics between July 2024 and June 2027. Patients within 6 months postpartum receiving HM treatment will be included. Data collection may continue for up to 8 weeks, encompassing demographic information, medical history, HM prescriptions, AEs, and concomitant medication use. Adverse events are self-reported by patients, and their causality is examined using World Health Organization-Uppsala Monitoring Centre causality assessment and the Naranjo algorithm score. Data collection and entry conform to standard operating procedures. Discussion : This study represents the first large-scale, multicenter registry examining HM use during the postpartum period in KM clinics. By systematically collecting real-world data on AEs associated with postpartum HM use, we aim to establish a comprehensive safety database for individual HM and constituent herbs. Our findings will provide valuable insights for practitioners and patients, potentially improving active pharmacovigilance on HM and enhancing postpartum care outcomes for mothers and infants. Trial Registration : The registry was registered with the Clinical Research Information Service (https://cris.nih.go.kr/cris/index/index.do) on June 20, 2024 (KCT0009552). postpartum period herbal medicine safety adverse events registry 1. Background Childbirth, although a natural and universal process, imposes considerable stress on the mother’s body, often resulting in a debilitated condition and a low quality of life [ 1 , 2 ]. Studies show that 49–94% of women experience at least one health issue up to 8 weeks postpartum [ 3 , 4 ]. These issues include fatigue [ 5 – 9 ], headache [ 10 – 12 ], musculoskeletal pain [ 8 , 13 , 14 ], urinary incontinence [ 15 – 17 ], and depression [ 18 – 21 ], often persisting beyond the first year postpartum. These prevalent and prolonged health problems significantly affect the well-being of both mothers and their children [ 22 ]. This situation highlights the need for safe and effective postpartum care strategies, leading many to consider herbal medicine (HM) as a treatment option [ 23 , 24 ]. Herbal medicine offers various potential benefits for postpartum women. Studies have shown that HM can mitigate postpartum pain [ 25 ]. Additionally, when used in conjunction with conventional treatments, HM may alleviate postpartum depression [ 26 ]. In East Asian countries, where HM is integrated into national healthcare systems, its use in postpartum care is particularly prevalent, with high satisfaction among consumers. Nevertheless, the lack of safety data on HM for both mothers and infants remains a considerable concern, possibly deterring some from using HM [ 23 , 27 ]. For instance, a study in Taiwan found that, while breastfeeding mothers were more likely to use HM, consumers of traditional Chinese herbs showed high lead concentrations in their breast milk, emphasizing the importance of safety monitoring [ 28 ]. This global context underscores the urgent need for rigorous safety studies on postpartum HM use. In South Korea, Korean Medicine (KM) plays an active role in addressing postpartum symptoms, with HM commonly used alongside acupuncture as the standard treatment method. According to a study on the satisfaction of mothers who received postpartum treatment with KM during the early postpartum period, 78.68% indicated a willingness to use KM again in future childbirths [ 29 ], while satisfaction with HM treatment was notably high at 72.13% [ 30 ]. Numerous local governments in South Korea support the use of HM post-delivery by subsidizing expenses, further indicating its perceived value in postpartum care [ 30 ]. However, South Korea’s drug utilization review service does not provide adverse event (AE) information related to HM. While some national statistics provide estimates on the incidence rate of AEs related to HM, these figures are based on patient reports or survey data, lacking expert case evaluations and detailed information on specific HM treatments [ 31 ]. Moreover, some reported AEs may not be directly attributable to HM, underscoring the importance of assessing a clear causal relationship [ 32 ]. This lack of comprehensive safety data creates a significant gap in our understanding of the risks associated with postpartum HM use. To address these concerns, especially the lack of safety information from official sources, this study aims to establish a registry for those receiving HM treatment at primary care institutions, specifically KM clinics. Because KM clinics account for approximately 96% of KM institutions in South Korea [ 33 ], research based on primary care KM clinics is crucial for collecting representative clinical data on KM. Through the systematic collection of data on the constituents of HM, details of AEs, and causality assessment, we seek to provide evidence for the safety monitoring of HM administration during the postpartum period. The primary research questions of this study are as follows: (1) What is the incidence rate of AEs following the use of postpartum HM? (2) Which HMs and constituent herbs are associated with specific AEs? (3) What is the cause of the observed AEs? We hypothesize that while some AEs may be observed, the overall safety profile of postpartum HM use is favorable when properly administered under KM doctors’ professional supervision. This study represents the first nationwide multicenter registry examining the use of HM during the postpartum period in KM clinics across South Korea. By providing comprehensive safety data, this research aims to contribute to evidence-based clinical practice in South Korea and ultimately enhance patient safety for both mothers and infants. 2. Methods 2.1. Objective The primary objective of the SAFEty of HErbal medicine REgistry in Korean Medicine clinics (SAFEHERE-KM) registry is to systematically collect and analyze clinical data on AEs related to HM treatment in postpartum patients in South Korea. This web-based registry will collect patient characteristics, details of HM prescriptions, and AE information, including causality assessment of any AEs that arise during HM treatment using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment [ 34 ] and the Naranjo algorithm score [ 35 , 36 ]. By establishing AE monitoring databases, this registry further aims to contribute to the development of an active pharmacovigilance system for HM in South Korea. 2.2. Study design The SAFEHERE-KM registry is a multicenter, prospective, observational study designed to collect data on routine clinical care and associated AEs in postpartum women receiving HM treatment at KM clinics. This study aims to enroll at least 1,000 eligible patients between July 2024 and June 2027 based on a previous study suggesting that this sample size rapidly decreases variation when reporting AE incidence [ 37 ]. Using empirical observations of postpartum patient visits to participating KM clinics, we anticipate enrolling approximately 400 participants annually (approximately 27 patients per clinic per year). The participants are postpartum patients who voluntarily consent to the collection of their clinical data. This study does not introduce specific interventions. Instead, the patients receive individualized HM treatments as part of their routine postpartum care. Korean Medicine doctors prescribe HM at their discretion without restrictions. Throughout the treatment period, which may extend up to 8 weeks depending on the duration of prescribed HM use, we collect data on demographics, medical history, KM treatment details, HM prescriptions, AEs, and concomitant medication use. Adverse events are self-reported by the patients via an online survey and collected in online databases. To ensure consistency in data collection and entry, KM doctors will follow standard operating procedures (SOPs) specifically designed for this registry. Patients will be recruited from 15 Jayoon KM clinics, a network specializing in gynecological disorders, located across South Korea. This network provides wide geographical coverage, including five clinics each in Seoul and Gyeonggi-do, as well as clinics in Jeju Province, Busan, Incheon, Daejeon, and Daegu (Supplemental figure). The registry was registered in the Clinical Research Information Service (KCT0009552). Recruitment started on July 7, 2024. 2.3. Eligibility criteria This registry enrolls patients diagnosed with complications predominantly related to the puerperium (O85–O92 of the International Statistical Classification of Diseases-10) or puerperal wind disorder (U32.7 of the Korean Standard Classification of Diseases-8). Puerperal wind disorder indicates a set of symptoms including pain and autonomic disturbance caused by inadequate body care after childbirth [ 1 ]. Women who have visited primary KM clinics within six months after giving birth and have been prescribed HM for postpartum recovery are included (Table 1 ). Table 1 Inclusion and exclusion criteria Inclusion criteria Exclusion criteria • Women aged ≥ 19 years • Have visited primary KM clinics within 6 months postpartum (calculated from the date of delivery) and are undergoing HM treatment for postpartum recovery • Did not consent to participate • Deemed inappropriate for participation in this study 2.4. Recruitment Participants will be enrolled at 15 primary KM clinics that offer postpartum care. Recruitment posters will be placed at the entrance of each clinic to encourage voluntary participation in this study. Health professionals in the clinic will thoroughly explain the study’s purpose and procedures—including data use, confidentiality, and sharing with third parties for the purpose of analysis—and obtain informed consent from potential participants who meet the inclusion criteria prior to data collection. Participants may withdraw from the study at any time during the study period without affecting their clinical treatments. 2.5. Outcomes For participants who meet the inclusion criteria and voluntarily sign the written informed consent form, we will assign a study registration number. We will then collect the following data for up to 8 weeks while they are taking HM: Demographics: Date of birth and age Anthropometric measurements: Height and weight Medical history (maternal health and delivery details): Delivery information (date and mode of delivery and gestational age), obstetric history (number of pregnancies, full-term births, preterm births, miscarriages, and surviving children), high-risk pregnancy factors (advanced maternal age (≥ 35 years), in vitro fertilization, gestational hypertension, and gestational diabetes), and newborn information (demographics, birth details, and feeding methods) Details of HM prescription: Name of prescribed HM, start date of administration, composition (herbs and doses), total and one-day dose of HM, and duration of HM administration Other KM treatments: Concurrent treatments, such as acupuncture, moxibustion, cupping, Chuna manipulation, and KM physical therapy Details of AEs: The occurrence of AEs is monitored at each visit during HM intake for up to 8 weeks. If an AE occurs, the collected data include the AE start date, symptoms, outcome, severity, actions taken, recurrence after the reintroduction of the suspected HM, treatment methods for the AE, and concurrent medications. Follow-up telephone interviews may be conducted for detailed information and causality assessments. Table 2 presents the details of the data collection and the study schedule. Table 2. Study schedule Timepoint Visit 1 Subsequent visits Endpoint Baseline 2,4,6,8 weeks after taking HM 1 Follow-up completion 3 Data collected from KM doctor Patient KM doctor Informed consent O Demographics O Diagnosis O Eligibility screening O Anthropometrics O Medical history O Concomitant medication O O O KM treatment information Details of HM prescription O Other KM treatments O Check for AEs Occurrence status O O Details of AEs 2 O O 1 Visits 3, 4, and 5 may be conducted if HM intake continues, with the process occurring at 2-week intervals for up to 8 weeks. 2 Data are collected only in the presence of AEs. 3 Follow-up completion is conducted once data collection on AEs is finalized or when HM administration is completed. Abbreviations: HM, herbal medicine; KM, Korean Medicine; AEs, adverse events. 2.6. Data management and quality control For data collection, we will use the myTrial Electronic Data Capture system (NIKOM, Gyeongsan, Republic of Korea), an electronic case report form (e-CRF) system validated by National Agency for Korean Medicine Innovative Technologies Development. Each clinic’s KM doctor can access the data entry form via the web server (https://www.nikom.or.kr/ecrf/service/Login) from a remote computer with internet access by logging in using the credentials provided by the website administrator. Each case entered into the registry will be reviewed regularly, and data queries will be generated according to the data monitoring manual. Monitors regularly visit KM clinics to check the original registry records and research files, and they discuss and resolve any issues with the co-investigators and principal investigators at each institution. All data collected for this study will be securely stored on a dedicated server with strict access control permissions. 2.7. Statistical analysis and causality assessment Statistical analyses will be performed using R software (R & R of the Statistics Department of the University of Auckland, Auckland, New Zealand). For participants who withdraw consent for continued follow-up, the data collected until withdrawal will be used in the analysis. For continuous variables, the means and standard deviations will be presented. Categorical variables will be reported as frequencies and percentages. All statistical analyses will be performed using two-sided tests, with the significance level set at 5%. The incidence of AEs will be assessed by presenting the number of AEs as odds ratios with 95% confidence intervals. For any reported AEs, severity will be determined based on established criteria for assessing AE severity [38]. The causality of AEs will be evaluated using both the WHO-UMC causality assessment [34] and the Naranjo algorithm score [35, 36], referring to the approach used in similar previous studies [39, 40]. This evaluation will be carried out by an independent Adverse Reaction Assessment Committee affiliated with the Regional Drug Safety Center at the Korea Institute of Drug Safety and Risk Management. 2.8. Patient and public involvement Patients will not be involved in the design, conduct, and dissemination plans of this research, as this registry study aims to collect real-world data on routine clinical practice. 2.9. Safety considerations While AE data are collected for research purposes, the treatment and management of any AEs are conducted by KM doctors as part of routine clinical care, ensuring that the participants receive appropriate care throughout the study period. 2.10. Ethics and dissemination This registry protocol initially received approval (version 1.0, April 24, 2024) from the Institutional Review Board of Woosuk KM Hospital, Woosuk University, Jeonju, Republic of Korea (WSOH IRB H2404-01-01). Following amendments to the research plan, the updated protocol (version 1.1) was subsesquently approved on June 24, 2024. Any protocol amendments will be approved by the Institutional Review Board and communicated to all investigators. Informed written consent will be obtained from all participants, which will allow us to collect patient data as specified in the case report forms. The findings will be shared through publication in peer-reviewed journals and presentations at academic conferences. 3. Discussion This study outlines the protocol for SAFEHERE-KM, a prospective observational registry study designed to monitor the safety of HM during the postpartum period across multiple KM clinics in South Korea. The SAFEHERE-KM study is the first large-scale, multicenter registry specifically designed to assess the safety of HM during the postpartum period in primary KM clinics. This unique approach allows for the collection of real-world data on HM use in a setting where it is most commonly prescribed, potentially providing more representative and clinically relevant information than our previous study conducted in a KM hospital [41]. The puerperal period commonly extends beyond the initial 6–8 weeks when reproductive organ recovery is mostly complete. Many women continue to experience physical and mental burden because of childcare, household responsibilities, and stress. Insufficient care during this extended period can lead to various complications [1]. A previous survey has shown that mothers typically seek HM treatment at KM institutions around 13–14 weeks postpartum. Recognizing the need for prolonged health management, many local governments in Korea provide support for KM treatments for up to 6 months postpartum [30]. Therefore, we include women within 6 months of delivery in our registry. The decision to monitor AEs for up to 8 weeks after the initiation of HM treatment was based on clinical experience from participating KM doctors, who reported that most patients complete their HM treatments within this period. This approach allows us to maximize participant enrollment within our budget constraints while capturing the most relevant period of HM use in postpartum care. The anticipated results of this study have several important clinical implications. By systematically collecting data on AEs associated with postpartum HM use, we aim to establish a comprehensive safety database for individual HM and constituent herbs. This dataset will include AE symptoms and signs, frequency, and severity, thereby providing valuable insights for both practitioners and patients. Furthermore, the causality assessment of reported AEs will strengthen the evidence for HM safety, promoting the development of guidelines for HM monitoring and decision-making processes in postpartum care. A dataset on causal herbs, their dosages, and concomitant drugs will enable the advanced analysis of herb–herb and herb–drug interactions [42]. Methodologically, the SAFEHERE-KM study has several strengths. The use of standardized data collection procedures, including detailed SOPs and an e-CRF, ensures consistency and quality in data gathering across multiple sites. This study collects closely monitored, patient-reported AEs to prevent underreporting and collect patients’ viewpoints [43]. We recruit at least 1,000 patients to gain an in-depth understanding of the AEs associated with HM. Patients are being recruited from 15 geographically diverse KM clinics across South Korea to minimize selection bias. Moreover, through data collection in real-world clinical settings, our results may achieve high external validity, making the findings more applicable to clinical practice [44]. Nevertheless, some limitations of this study should be acknowledged. The recruitment of participants from a single network of KM clinics that specialize in gynecological disorders may limit the diversity of HM prescriptions. While KM doctors in this network prescribe personalized HM for individual patients instead of uniform prescriptions, this may not capture the full range of HM practices across South Korea. Additionally, reliance on patient-reported AEs may underestimate unfavorable clinical events [45], although this is mitigated by standardized reporting procedures and visits to KM clinics during routine medical treatment. Future research should build upon the foundation established by the SAFEHERE-KM study. The inclusion of a wider range of primary care institutions could provide more comprehensive evidence of HM use in postpartum care across various practice settings. Furthermore, long-term follow-up studies could offer insights into the long-term safety profile of postpartum HM use, which is beyond the scope of the current study. In conclusion, the SAFEHERE-KM study represents a significant step forward in building a robust evidence base for the safety of HM in postpartum care. By providing comprehensive safety data from primary care settings, this research has the potential to improve active pharmacovigilance on HM, ultimately enhancing health outcomes for both mothers and infants in the crucial postpartum period. The findings of this study will contribute not only to the field of KM but also to global integrative approaches to postpartum care. Abbreviations AE adverse event e-CRF electronic case report form HM herbal medicine KM Korean Medicine SAFEHERE-KM SAFEty of HErbal medicine REgistry in Korean Medicine clinics SOP standard operating procedure WHO-UMC World Health Organization Uppsala-Monitoring Centre Declarations Supplemental Figure. Locations of Korean Medicine clinics participating in the registry Ethics approval and consent to participate This registry protocol initially received approval (version 1.0, April 24, 2024) from the Institutional Review Board of Woosuk KM Hospital, Woosuk University, Jeonju, Republic of Korea (WSOH IRB H2404-01-01). Written informed consent is obtained from all participants before enrollment in the study. Consent for publication Not applicable Availability of data and materials As this is a study protocol, no datasets have been generated or analyzed yet. Therefore, data sharing is not applicable at this stage. Competing interests The authors declare no competing interests. Funding This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea, grant number: RS-2023-KH138688. The funding source had no input regarding the design or publication of the study. Authors’ contributions Conceptualization: Mi Ju Son, Anna Kim, Young-Eun Kim, Sungha Kim, and Eunbyul Cho Methodology: Sungha Kim, Su-Min Seo, and Young-Eun Kim Supervision: Mi Ju Son Project administration: Mi Ju Son Writing – original draft: Eunbyul Cho and Anna Kim Writing – review and editing: Eunbyul Cho, Anna Kim, Young-Eun Kim, Su-Min Seo, Sungha Kim, Jae-An Sin, Eunhee Lee, and Mi Ju Son Acknowledgments We thank the members of the Jayoon KM clinic network for their collaboration: Hee Eun Jung, Min Jae Gwak, Hwa Seon Ko, Ji Hyun Kim, Jun Hak Lee, Seo Kyung Kim, Hwang Jin Park, Ey Ryung Jung, Won Joon Cho, Chang Yun Lee, Jun Young Jo, Hyeon Ju Kim, Jong Soon Beak, Seul Ah Jang, Yu Jeong Choi, and Eun Ji Choi. References The Society of Korean Medicine Obstetrics and Gynecology: Korean Medicine Obstetrics & Gynecology, vol. 4. Seoul: Euisungdang; 2021. 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Gross AJ, Pisano CE, Khunsriraksakul C, Spratt DE, Park HS, Sun Y, Wang M, Zaorsky NG: Real-world data: applications and relevance to cancer clinical trials. Seminars in Radiation Oncology 2023, 33(4):374–385. Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S: Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 2009, 101(23):1624–1632. Additional Declarations No competing interests reported. Supplementary Files Supplementaryfigure.pptx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6911139\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Study protocol\",\"associatedPublications\":[],\"authors\":[{\"id\":476035412,\"identity\":\"a3cba1ec-298e-4474-abac-bf19815f737e\",\"order_by\":0,\"name\":\"Anna Kim\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Anna\",\"middleName\":\"\",\"lastName\":\"Kim\",\"suffix\":\"\"},{\"id\":476035414,\"identity\":\"75394b5f-f133-46b2-9c84-3bb9cb22cc06\",\"order_by\":1,\"name\":\"Eunbyul Cho\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Eunbyul\",\"middleName\":\"\",\"lastName\":\"Cho\",\"suffix\":\"\"},{\"id\":476035416,\"identity\":\"fd03c690-60d9-40ad-bc00-624cc9713e68\",\"order_by\":2,\"name\":\"Young-Eun Kim\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Young-Eun\",\"middleName\":\"\",\"lastName\":\"Kim\",\"suffix\":\"\"},{\"id\":476035417,\"identity\":\"31ceb2bc-7fed-4c99-a991-c4576281f32e\",\"order_by\":3,\"name\":\"Su-Min Seo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Su-Min\",\"middleName\":\"\",\"lastName\":\"Seo\",\"suffix\":\"\"},{\"id\":476035418,\"identity\":\"db871414-d5b6-47ca-8049-95a91ef3d953\",\"order_by\":4,\"name\":\"Sungha Kim\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sungha\",\"middleName\":\"\",\"lastName\":\"Kim\",\"suffix\":\"\"},{\"id\":476035420,\"identity\":\"17cbb398-bed8-4593-b53e-f727818ee646\",\"order_by\":5,\"name\":\"Jae-An Sin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jayoon Korean Medicine Clinic\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jae-An\",\"middleName\":\"\",\"lastName\":\"Sin\",\"suffix\":\"\"},{\"id\":476035422,\"identity\":\"53a49ba6-aff4-4baa-955d-37efd5a1fd98\",\"order_by\":6,\"name\":\"Eunhee Lee\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Woo-Suk University Korean Medicine Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Eunhee\",\"middleName\":\"\",\"lastName\":\"Lee\",\"suffix\":\"\"},{\"id\":476035424,\"identity\":\"70b4ece6-5811-4ec5-b005-e701f812fdfe\",\"order_by\":7,\"name\":\"Mi Ju Son\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYFCC8x8OSFQk8EB5CcRoOWB4wOIMaVoYjA9UtsFVEqFFt/FAwoGb89Jk+MUOsH34wJCWT1CL2YEDBw7O3JbDIzk7gXnmDIYcywbCWg42HJbcVsFjcDuBmZmHocKACFsOMxz+Oweq5Q9xWo4xHJBsyIFoYWDIIUbLGYYDEsfSgH5JbGbsMUgjQsuNM8wfJGqS7fmlkw8z/KhIJqyFQeIAjMXYwMBAhAYGBv4GYlSNglEwCkbBiAYAzMk+hpB/foIAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Korea Institute of Oriental Medicine\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Mi\",\"middleName\":\"Ju\",\"lastName\":\"Son\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-06-17 06:53:34\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6911139/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6911139/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":94064277,\"identity\":\"b584f918-dc2a-4f77-a21f-2a27963fd4f0\",\"added_by\":\"auto\",\"created_at\":\"2025-10-22 07:38:31\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":657259,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6911139/v1/3272582d-5f83-4b8d-8db5-86e48c8c262e.pdf\"},{\"id\":85568163,\"identity\":\"d6febdea-7e84-44b2-8e5b-07b54c10eac9\",\"added_by\":\"auto\",\"created_at\":\"2025-06-27 15:18:45\",\"extension\":\"pptx\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":2541871,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplementaryfigure.pptx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6911139/v1/0415680fdc924ad0137d0f92.pptx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"SAFEHERE-KM: A prospective multicenter registry-based observational study protocol on the safety of postpartum herbal medicine in Korean medicine clinics\",\"fulltext\":[{\"header\":\"1. Background\",\"content\":\"\\u003cp\\u003eChildbirth, although a natural and universal process, imposes considerable stress on the mother\\u0026rsquo;s body, often resulting in a debilitated condition and a low quality of life [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Studies show that 49\\u0026ndash;94% of women experience at least one health issue up to 8 weeks postpartum [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. These issues include fatigue [\\u003cspan additionalcitationids=\\\"CR6 CR7 CR8\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e], headache [\\u003cspan additionalcitationids=\\\"CR11\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e], musculoskeletal pain [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e], urinary incontinence [\\u003cspan additionalcitationids=\\\"CR16\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e], and depression [\\u003cspan additionalcitationids=\\\"CR19 CR20\\\" citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e], often persisting beyond the first year postpartum. These prevalent and prolonged health problems significantly affect the well-being of both mothers and their children [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. This situation highlights the need for safe and effective postpartum care strategies, leading many to consider herbal medicine (HM) as a treatment option [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eHerbal medicine offers various potential benefits for postpartum women. Studies have shown that HM can mitigate postpartum pain [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. Additionally, when used in conjunction with conventional treatments, HM may alleviate postpartum depression [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]. In East Asian countries, where HM is integrated into national healthcare systems, its use in postpartum care is particularly prevalent, with high satisfaction among consumers. Nevertheless, the lack of safety data on HM for both mothers and infants remains a considerable concern, possibly deterring some from using HM [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. For instance, a study in Taiwan found that, while breastfeeding mothers were more likely to use HM, consumers of traditional Chinese herbs showed high lead concentrations in their breast milk, emphasizing the importance of safety monitoring [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. This global context underscores the urgent need for rigorous safety studies on postpartum HM use.\\u003c/p\\u003e \\u003cp\\u003eIn South Korea, Korean Medicine (KM) plays an active role in addressing postpartum symptoms, with HM commonly used alongside acupuncture as the standard treatment method. According to a study on the satisfaction of mothers who received postpartum treatment with KM during the early postpartum period, 78.68% indicated a willingness to use KM again in future childbirths [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e], while satisfaction with HM treatment was notably high at 72.13% [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. Numerous local governments in South Korea support the use of HM post-delivery by subsidizing expenses, further indicating its perceived value in postpartum care [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eHowever, South Korea\\u0026rsquo;s drug utilization review service does not provide adverse event (AE) information related to HM. While some national statistics provide estimates on the incidence rate of AEs related to HM, these figures are based on patient reports or survey data, lacking expert case evaluations and detailed information on specific HM treatments [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e]. Moreover, some reported AEs may not be directly attributable to HM, underscoring the importance of assessing a clear causal relationship [\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e]. This lack of comprehensive safety data creates a significant gap in our understanding of the risks associated with postpartum HM use.\\u003c/p\\u003e \\u003cp\\u003eTo address these concerns, especially the lack of safety information from official sources, this study aims to establish a registry for those receiving HM treatment at primary care institutions, specifically KM clinics. Because KM clinics account for approximately 96% of KM institutions in South Korea [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e], research based on primary care KM clinics is crucial for collecting representative clinical data on KM. Through the systematic collection of data on the constituents of HM, details of AEs, and causality assessment, we seek to provide evidence for the safety monitoring of HM administration during the postpartum period.\\u003c/p\\u003e \\u003cp\\u003eThe primary research questions of this study are as follows: (1) What is the incidence rate of AEs following the use of postpartum HM? (2) Which HMs and constituent herbs are associated with specific AEs? (3) What is the cause of the observed AEs? We hypothesize that while some AEs may be observed, the overall safety profile of postpartum HM use is favorable when properly administered under KM doctors\\u0026rsquo; professional supervision.\\u003c/p\\u003e \\u003cp\\u003eThis study represents the first nationwide multicenter registry examining the use of HM during the postpartum period in KM clinics across South Korea. By providing comprehensive safety data, this research aims to contribute to evidence-based clinical practice in South Korea and ultimately enhance patient safety for both mothers and infants.\\u003c/p\\u003e\"},{\"header\":\"2. Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.1. Objective\\u003c/h2\\u003e \\u003cp\\u003eThe primary objective of the SAFEty of HErbal medicine REgistry in Korean Medicine clinics (SAFEHERE-KM) registry is to systematically collect and analyze clinical data on AEs related to HM treatment in postpartum patients in South Korea. This web-based registry will collect patient characteristics, details of HM prescriptions, and AE information, including causality assessment of any AEs that arise during HM treatment using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment [\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e] and the Naranjo algorithm score [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. By establishing AE monitoring databases, this registry further aims to contribute to the development of an active pharmacovigilance system for HM in South Korea.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.2. Study design\\u003c/h2\\u003e \\u003cp\\u003eThe SAFEHERE-KM registry is a multicenter, prospective, observational study designed to collect data on routine clinical care and associated AEs in postpartum women receiving HM treatment at KM clinics. This study aims to enroll at least 1,000 eligible patients between July 2024 and June 2027 based on a previous study suggesting that this sample size rapidly decreases variation when reporting AE incidence [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e]. Using empirical observations of postpartum patient visits to participating KM clinics, we anticipate enrolling approximately 400 participants annually (approximately 27 patients per clinic per year).\\u003c/p\\u003e \\u003cp\\u003eThe participants are postpartum patients who voluntarily consent to the collection of their clinical data. This study does not introduce specific interventions. Instead, the patients receive individualized HM treatments as part of their routine postpartum care. Korean Medicine doctors prescribe HM at their discretion without restrictions.\\u003c/p\\u003e \\u003cp\\u003eThroughout the treatment period, which may extend up to 8 weeks depending on the duration of prescribed HM use, we collect data on demographics, medical history, KM treatment details, HM prescriptions, AEs, and concomitant medication use. Adverse events are self-reported by the patients via an online survey and collected in online databases. To ensure consistency in data collection and entry, KM doctors will follow standard operating procedures (SOPs) specifically designed for this registry.\\u003c/p\\u003e \\u003cp\\u003ePatients will be recruited from 15 Jayoon KM clinics, a network specializing in gynecological disorders, located across South Korea. This network provides wide geographical coverage, including five clinics each in Seoul and Gyeonggi-do, as well as clinics in Jeju Province, Busan, Incheon, Daejeon, and Daegu (Supplemental figure).\\u003c/p\\u003e \\u003cp\\u003eThe registry was registered in the Clinical Research Information Service (KCT0009552). Recruitment started on July 7, 2024.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.3. Eligibility criteria\\u003c/h2\\u003e \\u003cp\\u003eThis registry enrolls patients diagnosed with complications predominantly related to the puerperium (O85\\u0026ndash;O92 of the International Statistical Classification of Diseases-10) or puerperal wind disorder (U32.7 of the Korean Standard Classification of Diseases-8). Puerperal wind disorder indicates a set of symptoms including pain and autonomic disturbance caused by inadequate body care after childbirth [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Women who have visited primary KM clinics within six months after giving birth and have been prescribed HM for postpartum recovery are included (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eInclusion and exclusion criteria\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"2\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eInclusion criteria\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eExclusion criteria\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026bull; Women aged\\u0026thinsp;\\u0026ge;\\u0026thinsp;19 years\\u003c/p\\u003e \\u003cp\\u003e\\u0026bull; Have visited primary KM clinics within 6 months postpartum (calculated from the date of delivery) and are undergoing HM treatment for postpartum recovery\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u0026bull; Did not consent to participate\\u003c/p\\u003e \\u003cp\\u003e\\u0026bull; Deemed inappropriate for participation in this study\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.4. Recruitment\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants will be enrolled at 15 primary KM clinics that offer postpartum care. Recruitment posters will be placed at the entrance of each clinic to encourage voluntary participation in this study. Health professionals in the clinic will thoroughly explain the study\\u0026rsquo;s purpose and procedures\\u0026mdash;including data use, confidentiality, and sharing with third parties for the purpose of analysis\\u0026mdash;and obtain informed consent from potential participants who meet the inclusion criteria prior to data collection. Participants may withdraw from the study at any time during the study period without affecting their clinical treatments.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.5. Outcomes\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFor participants who meet the inclusion criteria and voluntarily sign the written informed consent form, we will assign a study registration number. We will then collect the following data for up to 8 weeks while they are taking HM:\\u003c/p\\u003e\\n\\u003cul\\u003e\\n \\u003cli\\u003eDemographics: Date of birth and age\\u003c/li\\u003e\\n \\u003cli\\u003eAnthropometric measurements: Height and weight\\u003c/li\\u003e\\n \\u003cli\\u003eMedical history (maternal health and delivery details): Delivery information (date and mode of delivery and gestational age), obstetric history (number of pregnancies, full-term births, preterm births, miscarriages, and surviving children), high-risk pregnancy factors (advanced maternal age (\\u0026ge; 35 years), in vitro fertilization, gestational hypertension, and gestational diabetes), and newborn information (demographics, birth details, and feeding methods)\\u003c/li\\u003e\\n \\u003cli\\u003eDetails of HM prescription: Name of prescribed HM, start date of administration, composition (herbs and doses), total and one-day dose of HM, and duration of HM administration\\u003c/li\\u003e\\n \\u003cli\\u003eOther KM treatments: Concurrent treatments, such as acupuncture, moxibustion, cupping, Chuna manipulation, and KM physical therapy\\u003c/li\\u003e\\n \\u003cli\\u003eDetails of AEs: The occurrence of AEs is monitored at each visit during HM intake for up to 8 weeks. If an AE occurs, the collected data include the AE start date, symptoms, outcome, severity, actions taken, recurrence after the reintroduction of the suspected HM, treatment methods for the AE, and concurrent medications. Follow-up telephone interviews may be conducted for detailed information and causality assessments.\\u003c/li\\u003e\\n\\u003c/ul\\u003e\\n\\u003cp\\u003eTable 2 presents the details of the data collection and the study schedule.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2.\\u003c/strong\\u003e Study schedule\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"567\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eTimepoint\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eVisit 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eSubsequent visits\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eEndpoint\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eBaseline\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e2,4,6,8 weeks\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003eafter taking HM \\u003csup\\u003e1\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eFollow-up completion\\u003csup\\u003e3\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;Data collected from\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eKM doctor\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003ePatient\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eKM doctor\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eInformed consent\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eDemographics\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eDiagnosis\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eEligibility screening\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eAnthropometrics\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eMedical history\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eConcomitant medication\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eKM treatment\\u003c/p\\u003e\\n \\u003cp\\u003einformation\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eDetails of HM prescription\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eOther KM treatments\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eCheck for AEs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eOccurrence status\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eDetails of AEs \\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eO\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003csup\\u003e1\\u0026nbsp;\\u003c/sup\\u003eVisits 3, 4, and 5 may be conducted if HM intake continues, with the process occurring at 2-week intervals for up to 8 weeks.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003e2\\u003c/sup\\u003e Data are collected only in the presence of AEs.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003e3\\u003c/sup\\u003e Follow-up completion is conducted once data collection on AEs is finalized or when HM administration is completed.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eAbbreviations: HM, herbal medicine; KM, Korean Medicine; AEs, adverse events.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.6. Data management and quality control\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFor data collection, we will use the myTrial Electronic Data Capture system (NIKOM, Gyeongsan, Republic of Korea), an electronic case report form (e-CRF) system validated by National Agency for Korean Medicine Innovative Technologies Development. Each clinic\\u0026rsquo;s KM doctor can access the data entry form via the web server (https://www.nikom.or.kr/ecrf/service/Login) from a remote computer with internet access by logging in using the credentials provided by the website administrator. Each case entered into the registry will be reviewed regularly, and data queries will be generated according to the data monitoring manual. Monitors regularly visit KM clinics to check the original registry records and research files, and they discuss and resolve any issues with the co-investigators and principal investigators at each institution. All data collected for this study will be securely stored on a dedicated server with strict access control permissions.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.7. Statistical analysis and causality assessment\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eStatistical analyses will be performed using R software (R \\u0026amp; R of the Statistics Department of the University of Auckland, Auckland, New Zealand). For participants who withdraw consent for continued follow-up, the data collected until withdrawal will be used in the analysis. For continuous variables, the means and standard deviations will be presented. Categorical variables will be reported as frequencies and percentages. All statistical analyses will be performed using two-sided tests, with the significance level set at 5%. The incidence of AEs will be assessed by presenting the number of AEs as odds ratios with 95% confidence intervals.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eFor any reported AEs, severity will be determined based on established criteria for assessing AE severity [38]. The causality of AEs will be evaluated using both the WHO-UMC causality assessment [34] and the Naranjo algorithm score [35, 36], referring to the approach used in similar previous studies [39, 40]. This evaluation will be carried out by an independent Adverse Reaction Assessment Committee affiliated with the Regional Drug Safety Center at the Korea Institute of Drug Safety and Risk Management.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.8. Patient and public involvement\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients will not be involved in the design, conduct, and dissemination plans of this research, as this registry study aims to collect real-world data on routine clinical practice.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.9. Safety considerations\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWhile AE data are collected for research purposes, the treatment and management of any AEs are conducted by KM doctors as part of routine clinical care, ensuring that the participants receive appropriate care throughout the study period.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.10. Ethics and dissemination\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis registry protocol initially received approval (version 1.0, April 24, 2024) from the Institutional Review Board of Woosuk KM Hospital, Woosuk University, Jeonju, Republic of Korea (WSOH IRB H2404-01-01). Following amendments to the research plan, the updated protocol (version 1.1) was subsesquently approved on June 24, 2024. Any protocol amendments will be approved by the Institutional Review Board and communicated to all investigators. Informed written consent will be obtained from all participants, which will allow us to collect patient data as specified in the case report forms. The findings will be shared through publication in peer-reviewed journals and presentations at academic conferences.\\u003c/p\\u003e\"},{\"header\":\"3. Discussion\",\"content\":\"\\u003cp\\u003eThis study outlines the protocol for SAFEHERE-KM, a prospective observational registry study designed to monitor the safety of HM during the postpartum period across multiple KM clinics in South Korea.\\u003c/p\\u003e\\n\\u003cp\\u003eThe SAFEHERE-KM study is the first large-scale, multicenter registry specifically designed to assess the safety of HM during the postpartum period in primary KM clinics. This unique approach allows for the collection of real-world data on HM use in a setting where it is most commonly prescribed, potentially providing more representative and clinically relevant information than our previous study conducted in a KM hospital [41].\\u003c/p\\u003e\\n\\u003cp\\u003eThe puerperal period commonly extends beyond the initial 6–8 weeks when reproductive organ recovery is mostly complete. Many women continue to experience physical and mental burden because of childcare, household responsibilities, and stress. Insufficient care during this extended period can lead to various complications [1]. A previous survey has shown that mothers typically seek HM treatment at KM institutions around 13–14 weeks postpartum. Recognizing the need for prolonged health management, many local governments in Korea provide support\\u0026nbsp;for KM treatments for up to 6 months postpartum\\u0026nbsp;[30]. Therefore, we include women within 6 months of delivery in our registry. The decision to monitor AEs for up to 8 weeks after the initiation of HM treatment was based on clinical experience from participating KM doctors, who reported that most patients complete their HM treatments within this period. This approach allows us to maximize participant enrollment within our budget constraints while capturing the most relevant period of HM use in postpartum care.\\u003c/p\\u003e\\n\\u003cp\\u003eThe anticipated results of this study have several important clinical implications. By systematically collecting data on AEs associated with postpartum HM use, we aim to establish a comprehensive safety database for individual HM and constituent herbs. This dataset will include AE symptoms and signs, frequency, and severity, thereby providing valuable insights for both practitioners and patients. Furthermore, the causality assessment of reported AEs will strengthen the evidence for HM safety, promoting the development of guidelines for HM monitoring and decision-making processes in postpartum care. A dataset on causal herbs, their dosages, and concomitant drugs will enable the advanced analysis of herb–herb and herb–drug interactions [42].\\u003c/p\\u003e\\n\\u003cp\\u003eMethodologically, the SAFEHERE-KM study has several strengths. The use of standardized data collection procedures, including detailed SOPs and an e-CRF, ensures consistency and quality in data gathering across multiple sites. This study collects closely monitored, patient-reported AEs to prevent underreporting and collect patients’ viewpoints [43]. We recruit at least 1,000 patients to gain an in-depth understanding of the AEs associated with HM. Patients are being recruited from 15 geographically diverse KM clinics across South Korea to minimize selection bias. Moreover, through data collection in real-world clinical settings, our results may achieve high external validity, making the findings more applicable to clinical practice [44].\\u003c/p\\u003e\\n\\u003cp\\u003eNevertheless, some limitations of this study should be acknowledged. The recruitment of participants from a single network of KM clinics that specialize in gynecological disorders may limit the diversity of HM prescriptions. While KM doctors in this network prescribe personalized HM for individual patients instead of uniform prescriptions, this may not capture the full range of HM practices across South Korea. Additionally, reliance on patient-reported AEs may underestimate unfavorable clinical events [45], although this is mitigated by standardized reporting procedures and visits to KM clinics during routine medical treatment.\\u003c/p\\u003e\\n\\u003cp\\u003eFuture research should build upon the foundation established by the SAFEHERE-KM study. The inclusion of a wider range of primary care institutions could provide more comprehensive evidence of HM use in postpartum care across various practice settings. Furthermore, long-term follow-up studies could offer insights into the long-term safety profile of postpartum HM use, which is beyond the scope of the current study.\\u003c/p\\u003e\\n\\u003cp\\u003eIn conclusion, the SAFEHERE-KM study represents a significant step forward in building a robust evidence base for the safety of HM in postpartum care. By providing comprehensive safety data from primary care settings, this research has the potential to improve active pharmacovigilance on HM, ultimately enhancing health outcomes for both mothers and infants in the crucial postpartum period. The findings of this study will contribute not only to the field of KM but also to global integrative approaches to postpartum care.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eAE \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;\\u0026nbsp;adverse event\\u003c/p\\u003e\\n\\u003cp\\u003ee-CRF \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;electronic case report form\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eHM \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;herbal medicine\\u003c/p\\u003e\\n\\u003cp\\u003eKM \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;Korean Medicine\\u003c/p\\u003e\\n\\u003cp\\u003eSAFEHERE-KM SAFEty of HErbal medicine REgistry in Korean Medicine clinics\\u003c/p\\u003e\\n\\u003cp\\u003eSOP \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;\\u0026nbsp;standard operating procedure\\u003c/p\\u003e\\n\\u003cp\\u003eWHO-UMC \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;World Health Organization Uppsala-Monitoring Centre\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eSupplemental Figure.\\u003c/strong\\u003e Locations of Korean Medicine clinics participating in the registry\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis registry protocol initially received approval (version 1.0, April 24, 2024) from the Institutional Review Board of Woosuk KM Hospital, Woosuk University, Jeonju, Republic of Korea (WSOH IRB H2404-01-01). Written informed consent is obtained from all participants before enrollment in the study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAs this is a study protocol, no datasets have been generated or analyzed yet. Therefore, data sharing is not applicable at this stage.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by the Korea Health Technology R\\u0026amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health \\u0026amp; Welfare, Republic of Korea, grant number: RS-2023-KH138688. The funding source had no input regarding the design or publication of the study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors’ contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eConceptualization: Mi Ju Son, Anna Kim, Young-Eun Kim, Sungha Kim, and Eunbyul Cho\\u003c/p\\u003e\\n\\u003cp\\u003eMethodology: Sungha Kim, Su-Min Seo, and Young-Eun Kim\\u003c/p\\u003e\\n\\u003cp\\u003eSupervision: Mi Ju Son\\u003c/p\\u003e\\n\\u003cp\\u003eProject administration: Mi Ju Son\\u003c/p\\u003e\\n\\u003cp\\u003eWriting – original draft: Eunbyul Cho and Anna Kim\\u003c/p\\u003e\\n\\u003cp\\u003eWriting – review and editing: Eunbyul Cho, Anna Kim, Young-Eun Kim, Su-Min Seo, Sungha Kim, Jae-An Sin, Eunhee Lee, and Mi Ju Son\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe thank the members of the Jayoon KM clinic network for their collaboration: Hee Eun Jung, Min Jae Gwak, Hwa Seon Ko, Ji Hyun Kim, Jun Hak Lee, Seo Kyung Kim, Hwang Jin Park, Ey Ryung Jung, Won Joon Cho, Chang Yun Lee, Jun Young Jo, Hyeon Ju Kim, Jong Soon Beak, Seul Ah Jang, Yu Jeong Choi, and Eun Ji Choi.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eThe Society of Korean Medicine Obstetrics and Gynecology: Korean Medicine Obstetrics \\u0026amp; Gynecology, vol. 4. Seoul: Euisungdang; 2021.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMartin E, Fisher O, Tone J, Suldsuren N, Kularatna S, Beckmann M, Miller YD: Health-related quality of life and utility of maternity health states amongst post-partum Australians. \\u003cem\\u003ePLOS ONE\\u003c/em\\u003e 2024, 19(10):e0310913.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCooklin AR, Amir LH, Jarman J, Cullinane M, Donath SM, The CASTLE Study Team: Maternal physical health symptoms in the first 8 weeks postpartum among primiparous Australian women. \\u003cem\\u003eBirth\\u003c/em\\u003e 2015, 42(3):254\\u0026ndash;260.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMeyling MMG, Frieling ME, Vervoort JPM, Feijen-de Jong EI, Jansen DEMC: Health problems experienced by women during the first year postpartum: a systematic review. \\u003cem\\u003eEur J Midwifery\\u003c/em\\u003e 2023, 7:42.\\u003c/span\\u003e\\u003c/li\\u003e 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and method of birth. \\u003cem\\u003eBirth\\u003c/em\\u003e 2002, 29(2):83\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBakker M, van der Beek AJ, Hendriksen IJ, Bruinvels DJ, van Poppel MN: Predictive factors of postpartum fatigue: a prospective cohort study among working women. \\u003cem\\u003eJ Psychosom Res\\u003c/em\\u003e 2014, 77(5):385\\u0026ndash;390.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGoldszmidt E, Kern R, Chaput A, Macarthur A: The incidence and etiology of postpartum headaches: a prospective cohort study. \\u003cem\\u003eCan J Anaesth\\u003c/em\\u003e 2005, 52(9):971\\u0026ndash;977.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKlein AM, Loder E: Postpartum headache. \\u003cem\\u003eInt J Obstey Anesth\\u003c/em\\u003e 2010, 19(4):422\\u0026ndash;430.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAnzola GP, Brighenti R, Cobelli M, Giossi A, Mazzucco 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30(2):239\\u0026ndash;245.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAcharya TA, Trivedi MD, Joshi KJ, Chhaiya SB, Mehta DS: A study of agreement between WHO-UMC causality assessment system and the Naranjo algorithm for causality assessment of adverse drug reactions observed in medical ICU of a tertiary care teaching hospital. \\u003cem\\u003eBiomed Pharmacol J\\u003c/em\\u003e 2020, 13(1):79\\u0026ndash;83.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLessing C, Schmitz A, Albers B, Schrappe M: Impact of sample size on variation of adverse events and preventable adverse events: systematic review on epidemiology and contributing factors. \\u003cem\\u003eQual Saf Health Care\\u003c/em\\u003e 2010, 19(6):e24.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKim Y, Kim SE, Kim AJ, Kim M, Cho E, Suh S, Cho Y, Lee DE, Choi E, Kang H-R \\u003cem\\u003eet al\\u003c/em\\u003e: Incidence and risk factors of adverse drug 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E, Son MJ: Safety of herbal medicine in the postpartum period of a Korean Medicine hospital and postpartum care centre: protocol of a registry study (SAFEHERE-PC). \\u003cem\\u003eBMJ Open\\u003c/em\\u003e 2024, 14(8):e086645.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChoudhury A, Singh PA, Bajwa N, Dash S, Bisht P: Pharmacovigilance of herbal medicines: concerns and future prospects. \\u003cem\\u003eJ Ethnopharmacol\\u003c/em\\u003e 2023, 309:116383.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBanerjee AK, Okun S, Edwards IR, Wicks P, Smith MY, Mayall SJ, Flamion B, Cleeland C, Basch E: Patient-reported outcome measures in safety event reporting: PROSPER consortium guidance. \\u003cem\\u003eDrug Safety\\u003c/em\\u003e 2013, 36:1129\\u0026ndash;1149.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGross AJ, Pisano CE, Khunsriraksakul C, Spratt DE, Park HS, Sun Y, Wang M, Zaorsky NG: Real-world data: applications and relevance to cancer clinical trials. \\u003cem\\u003eSeminars in Radiation Oncology\\u003c/em\\u003e 2023, 33(4):374\\u0026ndash;385.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBasch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S: Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. \\u003cem\\u003eJ Natl Cancer Inst\\u003c/em\\u003e 2009, 101(23):1624\\u0026ndash;1632.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"postpartum period, herbal medicine, safety, adverse events, registry\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6911139/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6911139/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e: Postpartum conditions significantly affect maternal and infant health. In South Korea, herbal medicine (HM) is commonly used for postpartum care in Korean Medicine (KM), but safety data on it remain limited. This study outlines a multicenter KM clinic registry designed to investigate treatment information and adverse events (AEs) in patients taking postpartum HM. Our aim is to build evidence for evaluating the safety of HM.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e:\\u003cstrong\\u003e \\u003c/strong\\u003eThis prospective observational registry will enroll 1,000 postpartum patients from 15 KM clinics between July 2024 and June 2027. Patients within 6 months postpartum receiving HM treatment will be included. Data collection may continue for up to 8 weeks, encompassing demographic information, medical history, HM prescriptions, AEs, and concomitant medication use. Adverse events are self-reported by patients, and their causality is examined using World Health Organization-Uppsala Monitoring Centre causality assessment and the Naranjo algorithm score. Data collection and entry conform to standard operating procedures.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDiscussion\\u003c/strong\\u003e:\\u003cstrong\\u003e \\u003c/strong\\u003eThis study represents the first large-scale, multicenter registry examining HM use during the postpartum period in KM clinics. By systematically collecting real-world data on AEs associated with postpartum HM use, we aim to establish a comprehensive safety database for individual HM and constituent herbs. Our findings will provide valuable insights for practitioners and patients, potentially improving active pharmacovigilance on HM and enhancing postpartum care outcomes for mothers and infants.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial Registration\\u003c/strong\\u003e: The registry was registered with the Clinical Research Information Service (https://cris.nih.go.kr/cris/index/index.do) on June 20, 2024 (KCT0009552).\\u003c/p\\u003e\",\"manuscriptTitle\":\"SAFEHERE-KM: A prospective multicenter registry-based observational study protocol on the safety of postpartum herbal medicine in Korean medicine clinics\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-06-27 15:18:40\",\"doi\":\"10.21203/rs.3.rs-6911139/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"17236d19-65cc-4343-8596-339970134d42\",\"owner\":[],\"postedDate\":\"June 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-10-22T07:38:15+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-06-27 15:18:40\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6911139\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6911139\",\"identity\":\"rs-6911139\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}