{"paper_id":"4402f96f-5ad1-4f4b-9114-a8065fee873b","body_text":"Prevalence of hyperuricemia in adolescents from 2000 to 2019 in Asia: A meta-analysis | 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 Research article Prevalence of hyperuricemia in adolescents from 2000 to 2019 in Asia: A meta-analysis Lihui Chen, Shuguang Han, Fengjing Liu, Si Chen, Xiaoting Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-16198/v2 This work is licensed under a CC BY 4.0 License Status: Under Review Version 2 posted 3 You are reading this latest preprint version Show more versions Abstract Background : Studies of the prevalence of hyperuricemia in adolescents have been limited to specific areas and the prevalence in Asia is unknown. Objectives : This study was to determine the prevalence of hyperuricemia in adolescents in Asia from 2000 to 2019. Data sources : A comprehensive search was conducted to identify all relevant cross-sectional studies in Pubmed, Embase, and Cochrane library databases. Study eligibility criteria : “hyperuricemia” and “adolescent” were the two critical inclusion criteria. Participants, and interventions : Adolescents; Study appraisal and synthesis methods : Two reviewers independently extracted data and assessed study quality using STROBE check list. Extracted information included the first author, study year, country, publication year, sample size, number of cases, and age of onset. Heterogeneity among studies was evaluated using the Q test and quantified using the I 2 statistic. Subgroup analyses were performed to identify the source of the heterogeneity. The possibility of publication bias was assessed using Egger’s test. Results : The meta-analysis included 11 articles. The pooled prevalence of hyperuricemia in adolescents in Asia was 15.4% (95% CI 9.5-21.2%) and the prevalence of adolescents in Taiwan was higher than that in mainland China. The prevalence in coastal areas was higher than that in inland areas. The prevalence of men was higher than that of women. After excluding the high prevalence study in Taiwan, the prevalence of adolescents has been increasing year by year. Publication bias was observed but the results did not change after a trim and fill test, indicating that the impact of this bias was likely insignificant. Limitations: The diagnostic criteria for hyperuricemia for adolescents varied among the studies; some studies used their own cut-off values for hyperuricemia in adolescents. Conclusions and implications of key findings: Hyperuricemia prevalence in adolescents is high and continues to increase. The prevalence varies with geography, gender, and time. Effective measures should be taken to prevent any further increase in the incidence of adolescent hyperuricemia. Systematic review registration number : Not applicable. Pediatrics prevalence hyperuricemia adolescents Figures Figure 1 Figure 2 Background Hyperuricemia has been kept on increasing in worldwide. Long-term hyperuricemia can cause gout and complications such as hypertension, cardiovascular disease, and chronic kidney disease (1). What ’s more serious is that its complcations are more harmful in adolescents which were defined as people aged 10–19 years by The World Health Organization (2) than those of adults. Both early onset and juvenile hyperuricemic patients have more severe dyslipidemia, impaired liver and renal dysfunction (3, 4). Up to now, there is no unanimously accepted cut off for hyperuricemia in adolescents. Data on the prevalence of hyperuricemia are lacking and hyperuricemia of children under the age of 20 which accounting for one-third of the population(5) has not attracted enough attention. The health status of the adolescent population is related to the future of the country. Obtaining an accurate prevalence of hyperuricemia is important to help us formulate appropriate local public health policies. Due to varied geographic locations that include diverse populations and different socioeconomic conditions, a unified epidemiological investigation about the prevalence of hyperuricemia in adolescents remains difficult, so we performed a meta-analysis to determine the prevalence of hyperuricemia in adolescents in Asia from 2000 to 2019. Methods Search strategy : The PubMed, Embase, and Cochrane library databases were searched. All articles on the prevalence of hyperuricemia in adolescents published from Jan 1, 2000 to Dec 10, 2019 were searched comprehensively using the keywords “Adolescents”, “Adolescence”, “Teens”, “Teen”, “Teenagers”, “Teenager”, “Youth”, “Youths”, “Adolescents, Female”, “Adolescent, Female”, “Female Adolescent” or “Female Adolescents”, “Adolescents, Male” or “Adolescent, Male”, “Male Adolescent” or “Male Adolescents”, “Child”, “Children”, “Hyperuricemia”, “asymptomatic hyperuricemia”, “HUA”, “HU”, “uric acid”, “Prevalence”, “Incidence”, “Epidemiology”, “Prevalences” , and “Incidences”. The following search strategy was used for Pubmed: (“Adolescent”[Mesh] OR “Adolescents” OR “Adolescence” OR “Teens” OR “Teen” OR “Teenagers” OR “Teenager” OR “Youth” OR “Youths” OR “Adolescents, Female” OR “Adolescent, Female” OR “Female Adolescent” OR “Female Adolescents” OR “Adolescents, Male” OR “Adolescent, Male” OR “Male Adolescent” OR “Male Adolescents”) AND (((“Gout”[Mesh]) OR “Hyperuricemia”[Mesh]) OR “asymptomatic hyperuricemia” OR “HUA” OR “HU” OR “uric acid”) AND (((“Prevalence”[Mesh]) OR “Incidence”[Mesh]) OR “Epidemiology”[Mesh] OR “Prevalences” OR “Incidences”) AND ((“2000/01/01”[PDat] : “2019/12/10”[Pdat]) AND Humans[Mesh] AND English[lang]) Searches were restricted to English publications and human studies. In addition, we searched the reference lists of all identified relevant studies. Our meta-analysis was conducted fundamentally according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA). Eligibility criteria: Papers were included if they met all of the following criteria: (1) all study participants were adolescents; (2) study data were general (i.e., population- rather than hospital-based); (3) original research; (4)cross-sectional studies ;(5) clearly stated study date; and (6) the most detailed study among duplicate studies of the same population (where applicable). Studies were excluded if they (1) were not original research, such as a review or case report, (2) included participants with concomitant diseases or a history of taking medications known to affect uric acid metabolism, (3) were animal studies or (4) cohort studies, or (5) had a small sample size;(6) low Study quality. Studies were imported into an EndNote X8 database and duplicates were removed. LHC and SGH screened the titles and abstracts of all studies against inclusion and exclusion criteria, respectively. The full text of potentially eligible studies were reviewed in duplicate by LHC and SGH against inclusion and exclusion criteria using a predesigned electronic assessment form. Discrepancies were resolved by discussion between the reviewers, with arbitration by a third reviewer (HBC) in case of disagreement. Definitions of Hyperuricemia : The diagnostic criteria used for hyperuricemia for adolescents varied among the studies; we united the measurement unit of uric acid as mg/dL and listed the criteria in Table 1. Data extraction : Two researchers (LHC, SGH) screened the literature independently and the screening results were cross-checked. According to the pre-designed data extraction table, the data were extracted independently, and the extraction results were cross-checked. The extracted data included the first author, study year, country, publication year, sample size, number of cases, and age of onset. We used the STROBE checklist to assess the quality of the research. Using this evaluation tool, we will evaluate six core components, including study design, participants, measurement, bias, descriptive data, and outcome data. Study quality was assessed independently by three reviewers (LHC, SGH, HBC). If two or three reviewers were in agreement, the study was included in the meta-analysis. If the score of the Study quality less than 4, we think it is low quality, and it will be eliminated in the final analysis. All data included in the study were tabulated. Data analysis : The statistical analyses were performed using STATA software (ver. 15.0; StataCorp., College Station, TX, USA). First, a heterogeneity test was performed on the included studies. The heterogeneity statistic, I 2 , was classified as follows: 25%, low heterogeneity; 50%, high heterogeneity; and 75%, high heterogeneity. If the heterogeneity among the included studies was low (I 2 ≤ 50%, P > 0.05), a fixed effect model was used; when there was high heterogeneity among the included studies (I 2 > 50%, P < 0.05), a random effect model was adopted. Subgroup analyses were also performed according to gender, age, and region. Results The search identified 1,980 potentially relevant papers, among which 1,797 remained after removing duplicate articles. The 1,735 articles that clearly did not meet the inclusion criteria were excluded after reading the title and abstract; the remaining 62 articles were further screened by reading the full text. 11 articles were eventually included in the meta-analysis. Figure 1 summarizes the literature screening process. The basic characteristics of the included articles are shown in Table 1. Pooled prevalence of hyperuricemia : As shown in Figure 2, the pooled prevalence of adolescent hyperuricemia was 15.4% (95% CI 9.5-21.2%) Subgroup analysis : We performed subgroup analyses of the prevalence of hyperuricemia in adolescents according to gender, age, region, study year, and residence (coastal or inland). The prevalence of hyperuricemia in adolescents in Asia was 15.4% (95% CI 9.5-21.2%), which fell to 10.8% (95% CI 4.7–16.9%) after excluding Taiwan. In Taiwan, the prevalence of adolescent hyperuricemia was 27.4% (95% CI 22.5–32.2%) and that in mainland China was 20.3% (95% CI 10.3-30.3%). The prevalence rate inland was 13.8% (95% CI 6.1-21.5%), while that in coastal areas was 16.0% (95% CI 8.9-23.0%). The prevalence rate was 22.1% (95% CI 10.6-33.5%) in males and 11.2% (95%CI 7.5-15.0%) in females. The prevalence rate in adolescents was highest in 2013–2018 (18.0%), followed by 2000–2005 (16.6%), and 2006–2011 (12.1%). After excluding the high-prevalence Taiwanese studies, the pooled prevalence of hyperuricemia in 2000–2005 was 4.6% (95% CI 4.1–5.1%), which was lower than that in 2006–2011 (7.5%; 95% CI 0.0–15.1%). The prevalence of hyperuricemia in adolescents was high in Asia, and higher in Taiwan than in mainland China. The prevalence of hyperuricemia in adolescents was also higher in males and coastal areas (Table 2). Analysis of heterogeneity and publication bias : Heterogeneity analysis showed very high heterogeneity in the studies of the prevalence of hyperuricemia in adolescents, and there was no decrease in heterogeneity in the subgroup analyses. Egger’s test also indicated publication bias. Then we performed a trim and fill method to address the problem of publication bias. However, it became unchanged after we applied the trim and fill method. Discussion We analyzed 11 studies of adolescent hyperuricemia conducted between 2000 and 2019, in the first meta-analysis of the prevalence of hyperuricemia in adolescents (to the best of our knowledge). The pooled prevalence of adolescent hyperuricemia was 15.4%, which is higher than that in adults in some regions. The prevalence of hyperuricemia among Chinese adults in 2009–2010 was 8.4% (17). In Saudi Arabia, the prevalence of hyperuricemia was 8.42% (18). The overall prevalence of hyperuricemia in Thai adults was 10.6%(19). The age-standardized prevalence of hyperuricemia in the general Korean population was 11.4%(20). In Italy, the prevalence was 11.9% during the period 2005–2009(21). In our study, the prevalence in adolescents in mainland China was 20.3% during the period 2000–2019, i.e., higher than that in adults; a meta-analysis of studies conducted in mainland China showed that the prevalence of hyperuricemia in adults was 13.3% during the period 2000–2014(22). The prevalence of hyperuricemia in adolescents is high and varies with geography, gender, and time. We found that the prevalence of hyperuricemia in adolescents in Asia was high, with the highest prevalence being in Taiwan. This may be because little research has been conducted in other regions, or simply because the prevalence of hyperuricemia in adolescents in Taiwan is high. In one study, the prevalence of hyperuricemia among aboriginal people in Taiwan was higher than that of non-aboriginal people(23). Our meta-analysis included two studies of Taiwan aborigines; these studies reported hyperuricemia prevalence rates in aboriginal adolescents of 22.9% and 35.3%, respectively, compared with 15.2% in adolescents in mainland China. In addition to environmental factors, the high prevalence of hyperuricemia among aboriginals in Taiwan may be associated with genetic factors (24). There are many aboriginal tribes in Taiwan, and since many laws prohibit non-aboriginal people from occupying aboriginal villages, there is a high rate of inbreeding within these tribes. Considering the impact of the prevalence of hyperuricemia among aboriginal people in Taiwan on the overall prevalence, we excluded the data for Taiwan aboriginal adolescents from the subgroup analysis of time, and found that the prevalence of hyperuricemia increased with the year. The prevalence of hyperuricemia during the period 2006–2011 was 1.5 times that in 2000–2005, and that of hyperuricemia during the period 2013–2018 was three times that in 2000–2005. The increasing prevalence of hyperuricemia in adolescents with time is in accordance with the increasing prevalence of diabetes (25, 26). With economic development, people’s living standards have improved, and their living and eating habits have changed. The prevalence of hyperuricemia in adolescents in coastal areas is higher than that in inland areas, which may also be related to lifestyle and eating habits. Miao et al .(27) showed that consumption of alcohol, meat, and seafood was associated with elevated blood uric acid levels in coastal residents of Shandong, China. Studies have reported higher hyperuricemia prevalence in adult men than in adult women (28-30). The high incidence of hyperuricemia in men is thought to be associated with the protective effects of estrogen in women (31). Kubota et al .(32)showed that the serum uric acid level increased steadily from 1 to 15 years of age, and there was a significant difference in uric acid levels between boys and girls after the age of 13 years. However, because of limited amount of data in these studies, we did not perform subgroup analyses of specific age groups. One limitation in our study was that the diagnostic criteria for hyperuricemia for adolescents varied among the studies; some studies used their own cut-off values for hyperuricemia in adolescents, which may also explain the high heterogeneity of prevalence. A study of schoolchildren in Brazil defined hyperuricemia as a serum uric acid ≥ 5.5 mg/dL(33). A study of school adolescents in northeast China used the 95 th percentile of serum uric acid in their sample as the cutoff value for hyperuricemia (34). There is no accepted threshold for defining hyperuricemia in children and adolescents. In the future, it will be necessary to determine optimal cutoff values for hyperuricemia in children in China and elsewhere. In summary, since previous studies have been limited to specific areas, our meta-analysis of adolescent hyperuricemia has important implications for public health policy. We found that the prevalence of hyperuricemia in adolescents is similar to that in adults, and is continuing to increase. The prevalence of hyperuricemia in Taiwanese aboriginals had a major impact on the overall prevalence. Large, well-designed multicenter surveys are needed to obtain information on the outcome and prognosis of hyperuricemia in adolescents. Effective measures should be taken to prevent the incidence of adolescent hyperuricemia from further increasing. Declarations Ethics approval and consent to participate : Not applicable Consent for publication : Not applicable Availability of data and materials: Not applicable Competing interests : The authors declare that they have no competing interests Funding: This work was supported by the National Key R&D Program of China, Synthetic Biology Research (Grant no. 2019YFA0904500) and the National Natural Science Foundation of China (No. 81870616 and 81670737). The funders had no role in the study design, data collection, analysis and interpretation of findings and made no contribution to writing the report. Authors' contributions: HBC designed the research, LHC and SGH analyzed the data and wrote the manuscript. FJL, XTC and SC participated in the revision of the manuscript. All authors were involved in the acquisition and/or interpretation of the data. H.B.C. was the guarantor of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. Acknowledgements: The authors thank all team members and participants from Shanghai Jiaotong University Affiliated Sixth People’s Hospital. References Abeles AM. Hyperuricemia, gout, and cardiovascular disease: an update. Curr Rheumatol Rep. 2015;17(3):13. Dick B, Ferguson BJ. Health for the world's adolescents: a second chance in the second decade. 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J Pediatr (Rio J). 2017;93(5):538-43. Li P, Jiang R, Li L, Liu C, Yang F, Qiu Y. Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China. J Pediatr Endocrinol Metab. 2014;27(5-6):525-32. Tables Table 1: Characteristics of studies on the prevalence of hyperuricemia. First Author Publication year Area Diagnostic criterion(mg/dL)(boy/girl) Inland/coastal Study year Age Sample size Case Prevalence (%) Study quality Suttikomin(6) 2018 Thailand ≥ 7/≥ 6 Inland 2013 12–18 689 135 19.6 5 Wang(7) 2015 Northeast China > 7/> 5.7 Inland 2010-2011 11-16 936 142 15.2 6 Chen(8) 2012 Taiwan ≥7.7/≥5.7 Coastal 2010 12-19 2090 535 25.6 5 Soylemezoglu(9) 2012 Turkey 5-11years:>6.6 >11years:>7.7/ >5.7 Coastal 2007-2008 5-18 3174 28 0.9 5 Hongo (10) 2010 Japan ≥7.0 Inland 2006-2008 12.1-15 958 65 6.8 5 Lee (11) 2007 Taiwan ≥7.0 Coastal 2001-2002 6-12 2284 524 22.9 6 Liu (12) 2003 Taiwan ＞7/>6 Coastal 2001 4-13 414 146 35.3 6 Ogura (13) 2004 Japan >7.6 Coastal 1999-2002 18-19 5338 240 4.5 5 Oyama (14) 2006 Japan ≥7.0 Coastal 2003 9.1-15 1729 86 5.0 5 Lee(15) 2019 Korea 10-11years:>6.6 12-18years:>7.7 />5.7 Coastal 2016-2017 10–18 1256 115 9.2 6 Lu(16) 2019 China ≥7.0 Coastal 2017-2018 13-19 9371 2379 25.3 7 Table 2: Stratified prevalence of hyperuricemia in adolencsents. Subgroups Prevalence(95%CI) Number of studies Heterogeneity Case/Total I 2 % P value Location Asia 15.4(9.5，21.2) 11 99.7 <0.001 4395/28239 Taiwan 27.4(22.5,32.2) 3 92.0 <0.001 1205/4788 China mainland 20.3(10.3,30.3) 2 98.5 <0.001 2521/10307 Coast/inland Inland 13.8(6.1,21.5) 3 97.2 <0.001 342/2583 Coast 16.0(8.9,23.0) 8 99.8 <0.001 4053/25656 Sex Male 22.1(10.6，33.5) 8 99.4 <0.001 2784/9070 Female 11.2(7.5，15.0) 8 99.1 <0.001 808/8567 Study Year 2000-2005 16.6(8.3,24.9) 4 99.5 <0.001 996/9765 4.6(4.1,5.1) * 2 0 0.422 326/7076 2006-2011 12.1(0.9，23.3) 4 99.6 <0.001 770/7158 7.5(0,15.1) * 3 99.0 <0.001 235/5068 2013-2018 18.0(6.6,29.5) 3 99.3 <0.001 2629/11316 Age 11-19 16.2(6.4,25.9) 6 99.7 <0.001 3496/19382 Total 15.4(9.5，21.2) 11 99.7 <0.001 4395/28239 * after excluding studies in Taiwan Supplementary Files PRISMA2009checklist.pdf Cite Share Download PDF Status: Under Review Version 2 posted Editor assigned by journal 30 Apr, 2020 Editor invited by journal 29 Apr, 2020 Submission checks completed at journal 02 Mar, 2020 You are reading this latest preprint version Show more versions 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. 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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-16198\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research article\",\"associatedPublications\":[],\"authors\":[{\"id\":539760,\"identity\":\"1bdb2267-0552-49e7-ad71-88e1a10b0596\",\"order_by\":1,\"name\":\"Lihui Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lihui\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":539761,\"identity\":\"bd77ca63-39aa-4589-a8aa-498e0fd99bec\",\"order_by\":2,\"name\":\"Shuguang Han\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shuguang\",\"middleName\":\"\",\"lastName\":\"Han\",\"suffix\":\"\"},{\"id\":539762,\"identity\":\"03c75a45-50c9-4450-b9bd-d77ca627b73c\",\"order_by\":3,\"name\":\"Fengjing Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Fengjing\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":539763,\"identity\":\"05d0438c-433a-4cef-9be1-c37cc403318d\",\"order_by\":4,\"name\":\"Si Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Si\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":539764,\"identity\":\"ddb4c861-b1b7-49fd-9835-f78ec56f7748\",\"order_by\":5,\"name\":\"Xiaoting Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiaoting\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":539765,\"identity\":\"5f305503-1b67-4d5e-a674-37bfb09ec372\",\"order_by\":6,\"name\":\"Haibing Chen\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYDACCQYGZsYGGwbGBhCPjXgtaQyMbSRqOQxVTYwW/tnNxx4X7jhvzzy/x4DhQ9lhoEgDAUvuHEs3nnnmdmJjG48B44xzh4EiB/BrMZDIMZPmbbudwAjUwszbdhgokkBIS/43oJZz9mAtf4nTksMG1HKAEeQwZkZitEjcSAM67Ewy0C9pBQd7zqXzSNwgoIV/RvIzad4ddvaGzYc3PvhRZi3HP4OAFjgwbGBgOACkeYhUDwTyxCsdBaNgFIyCkQYA/Qw+AD6sraoAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Haibing\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2020-03-02 15:26:47\",\"currentVersionCode\":2,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-16198/v2\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-16198/v2\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":1108006,\"identity\":\"54d5bf5d-9345-4fde-837b-214712d62a9e\",\"added_by\":\"auto\",\"created_at\":\"2020-05-15 17:04:21\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":43601,\"visible\":true,\"origin\":\"\",\"legend\":\"Flow diagram for the literature-search process. A total of 1,980 articles were identified. After screening for population base, study type, relevancy, and duplicates, 11 articles met our inclusion criteria.\",\"description\":\"\",\"filename\":\"Figure1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-16198/v2/Figure1.jpg\"},{\"id\":1108007,\"identity\":\"0e47819b-6410-410b-8fcb-23c5c3ac6a76\",\"added_by\":\"auto\",\"created_at\":\"2020-05-15 17:04:21\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":115155,\"visible\":true,\"origin\":\"\",\"legend\":\"Forest plot of the pooled prevalence of hyperuricemia in adolescents.\\nSummary the prevalence of hyperuricemia in adolescents. The area of the squares reflects the study-specific weight. Weights are from random effects analysis. The diamond and the vertical dotted line represent the pooled prevalence and 95%CI.\",\"description\":\"\",\"filename\":\"Figure2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-16198/v2/Figure2.jpg\"},{\"id\":13503844,\"identity\":\"8f36d257-f6ec-4d5d-a8fe-073beceb45b6\",\"added_by\":\"auto\",\"created_at\":\"2021-09-16 23:20:43\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":371677,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-16198/v2/9d9bd591-d659-4a30-9f0b-25458c15ff68.pdf\"},{\"id\":1108005,\"identity\":\"805a7b6d-f679-4d24-b26d-b9b3ccbc070d\",\"added_by\":\"auto\",\"created_at\":\"2020-05-15 17:04:21\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":58153,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"PRISMA2009checklist.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-16198/v2/PRISMA2009checklist.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Prevalence of hyperuricemia in adolescents from 2000 to 2019 in Asia: A meta-analysis\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eHyperuricemia has been kept on increasing in worldwide.\\u0026nbsp;Long-term hyperuricemia can cause gout and complications such as hypertension, cardiovascular disease, and chronic kidney disease (1). What \\u0026rsquo;s more serious\\u0026nbsp;is that its\\u0026nbsp;complcations\\u0026nbsp;are\\u0026nbsp;more harmful in\\u0026nbsp;adolescents which were defined as people aged 10\\u0026ndash;19 years by The World Health Organization (2) than those of adults.\\u0026nbsp;Both early onset\\u0026nbsp;and\\u0026nbsp;juvenile hyperuricemic\\u0026nbsp;patients\\u0026nbsp;have more\\u0026nbsp;severe\\u0026nbsp;dyslipidemia,\\u0026nbsp;impaired liver and renal dysfunction (3, 4). Up\\u0026nbsp;to\\u0026nbsp;now,\\u0026nbsp;there is no unanimously accepted cut off for hyperuricemia\\u0026nbsp;in adolescents.\\u0026nbsp;Data on the prevalence of hyperuricemia are lacking and hyperuricemia of children under the age of 20 which accounting for one-third of the population(5) has not attracted enough attention.\\u003c/p\\u003e\\n\\u003cp\\u003eThe health status of the adolescent\\u0026nbsp;population\\u0026nbsp;is related to\\u0026nbsp;the future of the\\u0026nbsp;country. Obtaining an accurate prevalence of hyperuricemia\\u0026nbsp;is important to help us formulate appropriate local\\u0026nbsp;public health policies. Due to varied geographic locations that include diverse\\u0026nbsp;populations and different socioeconomic conditions, a unified epidemiological investigation about the prevalence of\\u0026nbsp;hyperuricemia in adolescents remains difficult, so we performed a meta-analysis to determine the prevalence of hyperuricemia in adolescents in Asia from 2000 to 2019.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cem\\u003eSearch strategy\\u003c/em\\u003e: The PubMed, Embase, and Cochrane library databases were searched. All articles on the prevalence of hyperuricemia in adolescents published from Jan 1, 2000 to Dec 10, 2019 were searched comprehensively using the keywords \\u0026ldquo;Adolescents\\u0026rdquo;, \\u0026ldquo;Adolescence\\u0026rdquo;, \\u0026ldquo;Teens\\u0026rdquo;, \\u0026ldquo;Teen\\u0026rdquo;, \\u0026ldquo;Teenagers\\u0026rdquo;, \\u0026ldquo;Teenager\\u0026rdquo;, \\u0026ldquo;Youth\\u0026rdquo;, \\u0026ldquo;Youths\\u0026rdquo;, \\u0026ldquo;Adolescents, Female\\u0026rdquo;, \\u0026ldquo;Adolescent, Female\\u0026rdquo;, \\u0026ldquo;Female Adolescent\\u0026rdquo; or \\u0026ldquo;Female Adolescents\\u0026rdquo;, \\u0026ldquo;Adolescents, Male\\u0026rdquo; or \\u0026ldquo;Adolescent, Male\\u0026rdquo;, \\u0026ldquo;Male Adolescent\\u0026rdquo; or \\u0026ldquo;Male Adolescents\\u0026rdquo;, \\u0026ldquo;Child\\u0026rdquo;, \\u0026ldquo;Children\\u0026rdquo;, \\u0026ldquo;Hyperuricemia\\u0026rdquo;, \\u0026ldquo;asymptomatic hyperuricemia\\u0026rdquo;, \\u0026ldquo;HUA\\u0026rdquo;, \\u0026ldquo;HU\\u0026rdquo;, \\u0026ldquo;uric acid\\u0026rdquo;, \\u0026ldquo;Prevalence\\u0026rdquo;, \\u0026ldquo;Incidence\\u0026rdquo;, \\u0026ldquo;Epidemiology\\u0026rdquo;, \\u0026ldquo;Prevalences\\u0026rdquo; , and \\u0026ldquo;Incidences\\u0026rdquo;.\\u003c/p\\u003e\\n\\u003cp\\u003eThe following search strategy was used for Pubmed:\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e(\\u0026ldquo;Adolescent\\u0026rdquo;[Mesh] OR \\u0026ldquo;Adolescents\\u0026rdquo; OR \\u0026ldquo;Adolescence\\u0026rdquo; OR \\u0026ldquo;Teens\\u0026rdquo; OR \\u0026ldquo;Teen\\u0026rdquo; OR \\u0026ldquo;Teenagers\\u0026rdquo; OR \\u0026ldquo;Teenager\\u0026rdquo; OR \\u0026ldquo;Youth\\u0026rdquo; OR \\u0026ldquo;Youths\\u0026rdquo; OR \\u0026ldquo;Adolescents, Female\\u0026rdquo; OR \\u0026ldquo;Adolescent, Female\\u0026rdquo; OR \\u0026ldquo;Female Adolescent\\u0026rdquo; OR \\u0026ldquo;Female Adolescents\\u0026rdquo; OR \\u0026ldquo;Adolescents, Male\\u0026rdquo; OR \\u0026ldquo;Adolescent, Male\\u0026rdquo; OR \\u0026ldquo;Male Adolescent\\u0026rdquo; OR \\u0026ldquo;Male Adolescents\\u0026rdquo;) AND (((\\u0026ldquo;Gout\\u0026rdquo;[Mesh]) OR \\u0026ldquo;Hyperuricemia\\u0026rdquo;[Mesh]) OR \\u0026ldquo;asymptomatic hyperuricemia\\u0026rdquo; OR \\u0026ldquo;HUA\\u0026rdquo; OR \\u0026ldquo;HU\\u0026rdquo; OR \\u0026ldquo;uric acid\\u0026rdquo;) AND (((\\u0026ldquo;Prevalence\\u0026rdquo;[Mesh]) OR \\u0026ldquo;Incidence\\u0026rdquo;[Mesh]) OR \\u0026ldquo;Epidemiology\\u0026rdquo;[Mesh] OR \\u0026ldquo;Prevalences\\u0026rdquo; OR \\u0026ldquo;Incidences\\u0026rdquo;) AND ((\\u0026ldquo;2000/01/01\\u0026rdquo;[PDat] : \\u0026ldquo;2019/12/10\\u0026rdquo;[Pdat]) AND Humans[Mesh] AND English[lang])\\u003c/p\\u003e\\n\\u003cp\\u003eSearches were restricted to English publications and human studies. In addition, we searched the reference lists of all identified relevant studies. Our meta-analysis was conducted fundamentally according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eEligibility criteria:\\u003c/em\\u003e Papers were included if they met all of the following criteria: (1) all study participants were adolescents; (2) study data were general (i.e., population- rather than hospital-based); (3) original research; (4)cross-sectional studies ;(5) clearly stated study date; and (6) the most detailed study among duplicate studies of the same population (where applicable).\\u003c/p\\u003e\\n\\u003cp\\u003eStudies were excluded if they (1) were not original research, such as a review or case report, (2) included participants with concomitant diseases or a history of taking medications known to affect uric acid metabolism, (3) were animal studies or (4) cohort studies, or (5) had a small sample size;(6) low Study quality.\\u003c/p\\u003e\\n\\u003cp\\u003eStudies were imported into an EndNote X8 database and duplicates were removed. LHC and SGH screened the titles and abstracts of all studies against inclusion and exclusion criteria, respectively. The full text of potentially eligible studies were reviewed in duplicate by LHC and SGH against inclusion and exclusion criteria using a predesigned electronic assessment form. Discrepancies were resolved by discussion between the reviewers, with arbitration by a third reviewer (HBC) in case of disagreement.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eDefinitions of Hyperuricemia\\u003c/em\\u003e: The diagnostic criteria used for hyperuricemia for adolescents varied among the studies; we united the measurement unit of uric acid as mg/dL and listed the criteria in Table 1.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eData extraction\\u003c/em\\u003e: Two researchers (LHC, SGH) screened the literature independently and the screening results were cross-checked. According to the pre-designed data extraction table, the data were extracted independently, and the extraction results were cross-checked. The extracted data included the first author, study year, country, publication year, sample size, number of cases, and age of onset. We used the STROBE checklist to assess the quality of the research. Using this evaluation tool, we will evaluate six core components, including study design, participants, measurement, bias, descriptive data, and outcome data. Study quality was assessed independently by three reviewers (LHC, SGH, HBC). If two or three reviewers were in agreement, the study was included in the meta-analysis. If the score of the Study quality less than 4, we think it is low quality, and it will be eliminated in the final analysis. All data included in the study were tabulated.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eData analysis\\u003c/em\\u003e: The statistical analyses were performed using STATA software (ver. 15.0; StataCorp., College Station, TX, USA). First, a heterogeneity test was performed on the included studies. The heterogeneity statistic, I\\u003csup\\u003e2\\u003c/sup\\u003e, was classified as follows: 25%, low heterogeneity; 50%, high heterogeneity; and 75%, high heterogeneity. If the heterogeneity among the included studies was low (I\\u003csup\\u003e2\\u003c/sup\\u003e \\u0026le; 50%, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026nbsp;\\u0026gt;\\u0026nbsp;0.05), a fixed effect model was used; when there was high heterogeneity among the included studies (I\\u003csup\\u003e2\\u0026nbsp;\\u003c/sup\\u003e\\u0026gt;\\u0026nbsp;50%, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026nbsp;\\u0026lt;\\u0026nbsp;0.05), a random effect model was adopted. Subgroup analyses were also performed according to gender, age, and region.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eThe search identified 1,980 potentially relevant papers, among which 1,797 remained after removing duplicate articles. The 1,735 articles that clearly did not meet the inclusion criteria were excluded after reading the title and abstract; the remaining 62 articles were further screened by reading the full text. 11 articles were eventually included in the meta-analysis. Figure 1 summarizes the literature screening process. The basic characteristics of the included articles are shown in Table 1.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003ePooled prevalence of hyperuricemia\\u003c/em\\u003e: As shown in Figure 2, the pooled prevalence of adolescent hyperuricemia was 15.4% (95% CI 9.5-21.2%)\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eSubgroup analysis\\u003c/em\\u003e: We performed subgroup analyses of the prevalence of hyperuricemia in adolescents according to gender, age, region, study year, and residence (coastal or inland). The prevalence of hyperuricemia in adolescents in Asia was 15.4% (95% CI 9.5-21.2%), which fell to 10.8% (95% CI 4.7\\u0026ndash;16.9%) after excluding Taiwan. In Taiwan, the prevalence of adolescent hyperuricemia was 27.4% (95% CI 22.5\\u0026ndash;32.2%) and that in mainland China was 20.3% (95% CI 10.3-30.3%). The prevalence rate inland was 13.8% (95% CI 6.1-21.5%), while that in coastal areas was 16.0% (95% CI 8.9-23.0%). The prevalence rate was 22.1% (95% CI 10.6-33.5%) in males and 11.2% (95%CI 7.5-15.0%) in females. The prevalence rate in adolescents was highest in 2013\\u0026ndash;2018 (18.0%), followed by 2000\\u0026ndash;2005 (16.6%), and 2006\\u0026ndash;2011 (12.1%). After excluding the high-prevalence Taiwanese studies, the pooled prevalence of hyperuricemia in 2000\\u0026ndash;2005 was 4.6% (95% CI 4.1\\u0026ndash;5.1%), which was lower than that in 2006\\u0026ndash;2011 (7.5%; 95% CI 0.0\\u0026ndash;15.1%). The prevalence of hyperuricemia in adolescents was high in Asia, and higher in Taiwan than in mainland China. The prevalence of hyperuricemia in adolescents was also higher in males and coastal areas (Table 2).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eAnalysis of heterogeneity and publication bias\\u003c/em\\u003e: Heterogeneity analysis showed very high heterogeneity in the studies of the prevalence of hyperuricemia in adolescents, and there was no decrease in heterogeneity in the subgroup analyses. Egger\\u0026rsquo;s test also indicated publication bias. Then we performed a trim and fill method to address the problem of publication bias. However, it became unchanged after we applied the trim and fill method.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eWe analyzed 11 studies of adolescent hyperuricemia conducted between 2000 and 2019, in the first meta-analysis of the prevalence of hyperuricemia in adolescents (to the best of our knowledge). The pooled prevalence of adolescent hyperuricemia was 15.4%, which is higher than that in adults in some regions. The prevalence of hyperuricemia among Chinese adults in 2009\\u0026ndash;2010 was 8.4% (17). In Saudi Arabia, the prevalence of hyperuricemia was 8.42% (18). The overall prevalence of hyperuricemia in Thai adults was 10.6%(19). The age-standardized prevalence of hyperuricemia in the general Korean population was 11.4%(20). In Italy, the prevalence was 11.9% during the period 2005\\u0026ndash;2009(21). In our study, the prevalence in adolescents in mainland China was 20.3% during the period 2000\\u0026ndash;2019, i.e., higher than that in adults; a meta-analysis of studies conducted in mainland China showed that the prevalence of hyperuricemia in adults was 13.3% during the period 2000\\u0026ndash;2014(22).\\u003c/p\\u003e\\n\\u003cp\\u003eThe prevalence of hyperuricemia in adolescents is high and varies with geography, gender, and time. We found that the prevalence of hyperuricemia in adolescents in Asia was high, with the highest prevalence being in Taiwan. This may be because little research has been conducted in other regions, or simply because the prevalence of hyperuricemia in adolescents in Taiwan is high. In one study, the prevalence of hyperuricemia among aboriginal people in Taiwan was higher than that of non-aboriginal people(23). Our meta-analysis included two studies of Taiwan aborigines; these studies reported hyperuricemia prevalence rates in aboriginal adolescents of 22.9% and 35.3%, respectively, compared with 15.2% in adolescents in mainland China. In addition to environmental factors, the high prevalence of hyperuricemia among aboriginals in Taiwan may be associated with genetic factors (24). There are many aboriginal tribes in Taiwan, and since many laws prohibit non-aboriginal people from occupying aboriginal villages, there is a high rate of inbreeding within these tribes.\\u003c/p\\u003e\\n\\u003cp\\u003eConsidering the impact of the prevalence of hyperuricemia among aboriginal people in Taiwan on the overall prevalence, we excluded the data for Taiwan aboriginal adolescents from the subgroup analysis of time, and found that the prevalence of hyperuricemia increased with the year. The prevalence of hyperuricemia during the period 2006\\u0026ndash;2011 was 1.5 times that in 2000\\u0026ndash;2005, and that of hyperuricemia during the period 2013\\u0026ndash;2018 was three times that in 2000\\u0026ndash;2005. The increasing prevalence of hyperuricemia in adolescents with time is in accordance with the increasing prevalence of diabetes (25, 26). With economic development, people\\u0026rsquo;s living standards have improved, and their living and eating habits have changed. The prevalence of hyperuricemia in adolescents in coastal areas is higher than that in inland areas, which may also be related to lifestyle and eating habits. Miao \\u003cem\\u003eet al\\u003c/em\\u003e.(27) showed that consumption of alcohol, meat, and seafood was associated with elevated blood uric acid levels in coastal residents of Shandong, China.\\u003c/p\\u003e\\n\\u003cp\\u003eStudies have reported higher hyperuricemia prevalence in adult men than in adult women (28-30). The high incidence of hyperuricemia in men is thought to be associated with the protective effects of estrogen in women (31). Kubota \\u003cem\\u003eet al\\u003c/em\\u003e.(32)showed that the serum uric acid level increased steadily from 1 to 15 years of age, and there was a significant difference in uric acid levels between boys and girls after the age of 13 years. However, because of limited amount of data in these studies, we did not perform subgroup analyses of specific age groups.\\u003c/p\\u003e\\n\\u003cp\\u003eOne limitation in our study was that the diagnostic criteria for hyperuricemia for adolescents varied among the studies; some studies used their own cut-off values for hyperuricemia in adolescents, which may also explain the high heterogeneity of prevalence. A study of schoolchildren in Brazil defined hyperuricemia as a serum uric acid \\u0026ge; 5.5 mg/dL(33). A study of school adolescents in northeast China used the 95\\u003csup\\u003eth\\u003c/sup\\u003e percentile of serum uric acid in their sample as the cutoff value for hyperuricemia (34). There is no accepted threshold for defining hyperuricemia in children and adolescents. In the future, it will be necessary to determine optimal cutoff values for hyperuricemia in children in China and elsewhere.\\u003c/p\\u003e\\n\\u003cp\\u003eIn summary, since previous studies have been limited to specific areas, our meta-analysis of adolescent hyperuricemia has important implications for public health policy. We found that the prevalence of hyperuricemia in adolescents is similar to that in adults, and is continuing to increase. The prevalence of hyperuricemia in Taiwanese aboriginals had a major impact on the overall prevalence. Large, well-designed multicenter surveys are needed to obtain information on the outcome and prognosis of hyperuricemia in adolescents. Effective measures should be taken to prevent the incidence of adolescent hyperuricemia from further increasing.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003cstrong\\u003e: \\u003c/strong\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003cstrong\\u003e: \\u003c/strong\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials: \\u003c/strong\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003cstrong\\u003e:\\u003c/strong\\u003e The authors declare that they have no competing interests\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding: \\u003c/strong\\u003eThis work was supported by the National Key R\\u0026amp;D Program of China, Synthetic Biology Research (Grant no. 2019YFA0904500) and the National Natural Science Foundation of China (No. 81870616 and 81670737). The funders had no role in the study design, data collection, analysis and interpretation of findings and made no contribution to writing the report.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors' contributions:\\u003c/strong\\u003e HBC designed the research, LHC and SGH analyzed the data and wrote the manuscript. FJL, XTC and SC participated in the revision of the manuscript. All authors were involved in the acquisition and/or interpretation of the data. H.B.C. was the guarantor of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements: \\u003c/strong\\u003eThe authors thank all team members and participants from Shanghai Jiaotong University Affiliated Sixth People\\u0026rsquo;s Hospital.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eAbeles AM. Hyperuricemia, gout, and cardiovascular disease: an update. Curr Rheumatol Rep. 2015;17(3):13.\\u003c/li\\u003e\\n\\u003cli\\u003eDick B, Ferguson BJ. Health for the world's adolescents: a second chance in the second decade. J Adolesc Health. 2015;56(1):3-6.\\u003c/li\\u003e\\n\\u003cli\\u003eLu CC, Wu SK, Chen HY, Chung WS, Lee MC, Yeh CJ. Clinical characteristics of and relationship between metabolic components and renal function among patients with early-onset juvenile tophaceous gout. J Rheumatol. 2014;41(9):1878-83.\\u003c/li\\u003e\\n\\u003cli\\u003eChen JH, Yeh WT, Chuang SY, Wu YY, Pan WH. Gender-specific risk factors for incident gout: a prospective cohort study. Clin Rheumatol. 2012;31(2):239-45.\\u003c/li\\u003e\\n\\u003cli\\u003eClausen CE, Bazaid K, Azeem MW, Abdelrahim F, Elgawad AAA, Alamiri B, et al. Child and adolescent psychiatry training and services in the Middle East region: a current status assessment. Eur Child Adolesc Psychiatry. 2020;29(1):51-61.\\u003c/li\\u003e\\n\\u003cli\\u003eSuttikomin W, Leelahagul P, Khamvang S, Chaimongkol C, Chaiwut N. Obesity and serum uric acid in secondary school-age students of srinagarindra the princess mother school, Phayao, Thailand. Indian J Public Health. 2018;62(2):133-7.\\u003c/li\\u003e\\n\\u003cli\\u003eWang ZN, Li P, Jiang RH, Li L, Li X, Li L, et al. The association between serum uric acid and metabolic syndrome among adolescents in northeast China. Int J Clin Exp Med. 2015;8(11):21122-9.\\u003c/li\\u003e\\n\\u003cli\\u003eChen SC, Huang YF, Wang JD. Hyperferritinemia and hyperuricemia may be associated with liver function abnormality in obese adolescents. PLoS One. 2012;7(10):e48645.\\u003c/li\\u003e\\n\\u003cli\\u003eSoylemezoglu O, Duzova A, Yalcinkaya F, Arinsoy T, Suleymanlar G. Chronic renal disease in children aged 5-18 years: a population-based survey in Turkey, the CREDIT-C study. Nephrol Dial Transplant. 2012;27 Suppl 3:iii146-51.\\u003c/li\\u003e\\n\\u003cli\\u003eHongo M, Hidaka H, Sakaguchi S, Nakanishi K, Ichikawa M, Hirota N, et al. Association between serum uric acid levels and cardiometabolic risk factors among Japanese junior high school students. Circ J. 2010;74(8):1570-7.\\u003c/li\\u003e\\n\\u003cli\\u003eLee MS, Wahlqvist ML, Yu HL, Pan WH. Hyperuricemia and metabolic syndrome in Taiwanese children. Asia Pac J Clin Nutr. 2007;16 Suppl 2:594-600.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu CS, Li TC, Lin CC. The epidemiology of hyperuricemia in children of Taiwan aborigines. J Rheumatol. 2003;30(4):841-5.\\u003c/li\\u003e\\n\\u003cli\\u003eOgura T, Matsuura K, Matsumoto Y, Mimura Y, Kishida M, Otsuka F, et al. Recent trends of hyperuricemia and obesity in Japanese male adolescents, 1991 through 2002. Metabolism. 2004;53(4):448-53.\\u003c/li\\u003e\\n\\u003cli\\u003eOyama C, Takahashi T, Oyamada M, Oyamada T, Ohno T, Miyashita M, et al. Serum uric acid as an obesity-related indicator in early adolescence. Tohoku J Exp Med. 2006;209(3):257-62.\\u003c/li\\u003e\\n\\u003cli\\u003eLee JH. Prevalence of hyperuricemia and its association with metabolic syndrome and cardiometabolic risk factors in Korean children and adolescents: analysis based on the 2016-2017 Korea National Health and Nutrition Examination Survey. Korean J Pediatr. 2019;62(8):317-23.\\u003c/li\\u003e\\n\\u003cli\\u003eLu J, Sun W, Cui L, Li X, He Y, Liu Z, et al. A cross-sectional study on uric acid levels among Chinese adolescents. Pediatr Nephrol. 2019.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu H, Zhang XM, Wang YL, Liu BC. Prevalence of hyperuricemia among Chinese adults: a national cross-sectional survey using multistage, stratified sampling. J Nephrol. 2014;27(6):653-8.\\u003c/li\\u003e\\n\\u003cli\\u003eAl-Arfaj AS. Hyperuricemia in Saudi Arabia. Rheumatol Int. 2001;20(2):61-4.\\u003c/li\\u003e\\n\\u003cli\\u003eLohsoonthorn V, Dhanamun B, Williams MA. Prevalence of hyperuricemia and its relationship with metabolic syndrome in Thai adults receiving annual health exams. Arch Med Res. 2006;37(7):883-9.\\u003c/li\\u003e\\n\\u003cli\\u003eKim Y, Kang J, Kim GT. Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample. Clin Rheumatol. 2018;37(9):2529-38.\\u003c/li\\u003e\\n\\u003cli\\u003eTrifiro G, Morabito P, Cavagna L, Ferrajolo C, Pecchioli S, Simonetti M, et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis. 2013;72(5):694-700.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu R, Han C, Wu D, Xia X, Gu J, Guan H, et al. Prevalence of Hyperuricemia and Gout in Mainland China from 2000 to 2014: A Systematic Review and Meta-Analysis. Biomed Res Int. 2015;2015:762820.\\u003c/li\\u003e\\n\\u003cli\\u003eChungtei C. Hyperuricemia and gout among Taiwan Aborigines and Taiwanese-prevalence and risk factors. Chin Med J (Engl). 2003;116(7):965-7.\\u003c/li\\u003e\\n\\u003cli\\u003eWang WH, Chang SJ, Wang TN, Cheng LS, Feng YP, Chen CJ, et al. Complex segregation and linkage analysis of familial gout in Taiwanese aborigines. Arthritis Rheum. 2004;50(1):242-6.\\u003c/li\\u003e\\n\\u003cli\\u003ePan XR, Yang WY, Li GW, Liu J. Prevalence of diabetes and its risk factors in China, 1994. National Diabetes Prevention and Control Cooperative Group. Diabetes Care. 1997;20(11):1664-9.\\u003c/li\\u003e\\n\\u003cli\\u003eWang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, et al. Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013. JAMA. 2017;317(24):2515-23.\\u003c/li\\u003e\\n\\u003cli\\u003eMiao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, et al. Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol. 2008;35(9):1859-64.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu L, Lou S, Xu K, Meng Z, Zhang Q, Song K. Relationship between lifestyle choices and hyperuricemia in Chinese men and women. Clin Rheumatol. 2013;32(2):233-9.\\u003c/li\\u003e\\n\\u003cli\\u003eCui L, Meng L, Wang G, Yuan X, Li Z, Mu R, et al. Prevalence and risk factors of hyperuricemia: results of the Kailuan cohort study. Mod Rheumatol. 2017;27(6):1066-71.\\u003c/li\\u003e\\n\\u003cli\\u003eZhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-41.\\u003c/li\\u003e\\n\\u003cli\\u003eNicholls A, Snaith ML, Scott JT. Effect of oestrogen therapy on plasma and urinary levels of uric acid. Br Med J. 1973;1(5851):449-51.\\u003c/li\\u003e\\n\\u003cli\\u003eKubota M, Nagai A, Tang L, Tokuda M. Investigation on hyperuricemia in children with obesity or various pediatric disorders. Nucleosides Nucleotides Nucleic Acids. 2011;30(12):1051-9.\\u003c/li\\u003e\\n\\u003cli\\u003eReis LN, Renner JDP, Reuter CP, Horta JA, Paiva DN, Valim ARM, et al. Hyperuricemia is associated with low cardiorespiratory fitness levels and excess weight in schoolchildren. J Pediatr (Rio J). 2017;93(5):538-43.\\u003c/li\\u003e\\n\\u003cli\\u003eLi P, Jiang R, Li L, Liu C, Yang F, Qiu Y. Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China. J Pediatr Endocrinol Metab. 2014;27(5-6):525-32.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\\\"\\u003eTable 1: Characteristics of studies on the prevalence of hyperuricemia.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width: 4.5e+2pt;margin-left:-14.2pt;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width:42.3pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:.35pt .35pt 0in .35pt;height:25.7pt;\\\"\\u003e\\n \\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"color: rgb(0, 0, 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style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"color: rgb(0, 0, 0);\\\"\\u003e\\u003cspan style=\\\"font-size: 12px;\\\"\\u003e\\u003cspan style=\\\"font-family: Helvetica;\\\"\\u003e\\u003cspan style=\\\"line-height: 200%;\\\"\\u003e25.3\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:28.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:25.55pt;\\\"\\u003e\\n \\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"color: rgb(0, 0, 0);\\\"\\u003e\\u003cspan style=\\\"font-size: 12px;\\\"\\u003e\\u003cspan style=\\\"font-family: Helvetica;\\\"\\u003e\\u003cspan style=\\\"line-height: 200%;\\\"\\u003e7\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\u003cbr\\u003e\\n\\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\\\"\\u003eTable 2: Stratified prevalence of hyperuricemia in adolencsents.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width: 4.4e+2pt;border: none;border-collapse:collapse;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\" 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12px;\\\"\\u003e\\u003cspan style=\\\"font-family: Helvetica;\\\"\\u003ePrevalence(95%CI)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width:57.7pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:.3pt .3pt 0in .3pt;height:15.9pt;\\\"\\u003e\\n \\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"color: rgb(0, 0, 0);\\\"\\u003e\\u003cspan style=\\\"font-size: 12px;\\\"\\u003e\\u003cspan style=\\\"font-family: Helvetica;\\\"\\u003eNumber of studies\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" style=\\\"width:136.95pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:.3pt .3pt 0in .3pt;height:15.9pt;\\\"\\u003e\\n 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1.0pt;padding:.3pt .3pt 0in .3pt;height:19.6pt;\\\"\\u003e\\n \\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"color: rgb(0, 0, 0);\\\"\\u003e\\u003cspan style=\\\"font-size: 12px;\\\"\\u003e\\u003cspan style=\\\"font-family: Helvetica;\\\"\\u003e4395/28239\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;margin-bottom:.0001pt;line-height:200%;font-size:16px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cspan style=\\\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\\\"\\u003e* after excluding studies in Taiwan\\u003c/span\\u003e\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"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\":\"bmc-pediatrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bped\",\"sideBox\":\"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bped/default.aspx\",\"title\":\"BMC Pediatrics\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"prevalence, hyperuricemia, adolescents \",\"lastPublishedDoi\":\"10.21203/rs.3.rs-16198/v2\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-16198/v2\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e: Studies of the prevalence of hyperuricemia in adolescents have been limited to specific areas and the prevalence in Asia is unknown. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eObjectives\\u003c/strong\\u003e: This study was to determine the prevalence of hyperuricemia in adolescents in Asia from 2000 to 2019.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eData sources\\u003c/strong\\u003e: A comprehensive search was conducted to identify all relevant cross-sectional studies in Pubmed, Embase, and Cochrane library databases.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eStudy eligibility criteria\\u003c/strong\\u003e: “hyperuricemia” and “adolescent” were the two critical inclusion criteria. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eParticipants, and interventions\\u003c/strong\\u003e: Adolescents;\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eStudy appraisal and synthesis methods\\u003c/strong\\u003e: Two reviewers independently extracted data and assessed study quality using STROBE check list.\\u0026nbsp;Extracted information included the first author, study year, country, publication year, sample size, number of cases, and age of onset. Heterogeneity among studies was evaluated using the Q test and quantified using the I\\u003csup\\u003e2\\u003c/sup\\u003e statistic. Subgroup analyses were performed to identify the source of the heterogeneity. The possibility of publication bias was assessed using Egger’s test. \\u0026nbsp;\\u0026nbsp;\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e: The meta-analysis included 11 articles. The pooled prevalence of hyperuricemia in adolescents in Asia was 15.4% (95% CI 9.5-21.2%) and the prevalence of adolescents in Taiwan was higher than that in mainland China. The prevalence in coastal areas was higher than that in inland areas. The prevalence of men was higher than that of women. After excluding the high prevalence study in Taiwan, the prevalence of adolescents has been increasing year by year. Publication bias was observed but the results did not change after a trim and fill test, indicating that the impact of this bias was likely insignificant.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eLimitations:\\u003c/strong\\u003e The diagnostic criteria for hyperuricemia for adolescents varied among the studies; some studies used their own cut-off values for hyperuricemia in adolescents.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConclusions and implications of key findings:\\u003c/strong\\u003e Hyperuricemia prevalence in adolescents is high and continues to increase. The prevalence varies with geography, gender, and time. Effective measures should be taken to prevent any further increase in the incidence of adolescent hyperuricemia.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eSystematic review registration number\\u003c/strong\\u003e: Not applicable.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Prevalence of hyperuricemia in adolescents from 2000 to 2019 in Asia: A meta-analysis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":2,\"date\":\"2020-05-15 17:01:40\",\"doi\":\"10.21203/rs.3.rs-16198/v2\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2020-04-30T12:00:00+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2020-04-29T12:00:00+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2020-03-02T12:00:00+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-pediatrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bped\",\"sideBox\":\"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bped/default.aspx\",\"title\":\"BMC Pediatrics\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}},{\"code\":1,\"date\":\"2020-03-05 16:37:29\",\"doi\":\"10.21203/rs.3.rs-16198/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Major revision\",\"date\":\"2020-04-01T12:00:00+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2020-03-31T12:00:00+00:00\",\"index\":2,\"fulltext\":\"Recommendation: Major revisions required\\nForm responses:\\n---\\n\\nComments to Author:\\n---\\nManuscript number: BPED-D-20-00270\\nTitle: Global prevalence of hyperuricemia in adolescents from 2000 to 2019: A meta-analysis\\nGenerally, the authors deserve appreciations for producing this evidence. A pioneering analysis in the area, the produced evidence may play important role for further study. Major part of the study went nicely. However, there are certain limitations: the findings do not adequately address the aims; the methods lack clarity; the discussion is too narrow in scope. Hence, the author may need to improve the manuscript substantially. See my specific comments on each section below.\\nTitle: The title seems undeservedly broad: the analysis included only two of the 13 articles from outside of Asia. Hence, I do not believe the adequacy of the pooled prevalence of hyperuricemia to represent the wider world.\\nAbstract: Should provide a brief but optimal picture of the research synthesis. This abstract seems to lack many of the important descriptions of the overall analysis. It did not adequately justify the study. The methods section particularly is uninformative as it did not give the most expected descriptions (for example, on type of studies, selection criteria, management of bias [quality appraisal], and method of analysis). The result does not justify some of the concluding remarks (the third conclusion, for instance). The synthesists (authors) hinted the use of the PRISMA guideline in developing this report, but the write up showed poor adherence to the guideline.\\nIntroduction: this section provided important clarification. However, the synthesists need to elaborate it further by reviewing some additional pertinent literatures, textbooks and reports; it should be simple (free of gorgon words) enough for optimal understanding by the majority (if not all) of readers. It should clearly define some important concepts like hyperuricemia and adolescent. The meta-analysis is not well justified: What special interests does hyperuricemia hold about adolescents? What really is the synthesists want to achieve? They stated their aim as, \\\"to increase our understanding of adolescent hyperuricemia and enhance awareness…,\\\" which demands evidences on its more important aspects (such as its consequences, severity and causes) than its prevalence. Say differently, the output of the analysis poorly addressed the stated aim; the synthesists need to modify either the aim or input and throughput of the analysis.\\nMaterials and methods: This section lacks clarity. The authors must further clarify it by including their qualification to conduct this synthesis, the screening criteria, protocols followed (in developing the report), tools used to assess the quality of primary studies, the procedure followed in calculating the pooled prevalence (as the primary studies varied in their units of prevalence measurement), and so on. I feel that the quality of the primary studies should be considered as part of the inclusion criteria. Further, the quality appraisal tool they used to assess the quality of the primary studies is appropriate for the type of studies included in the research synthesis. Finally, it is not clear why and how they used both the non-fixed and fixed model effects to a singly research synthesis.\\nResult: The authors presented this section nicely. However, some concerns, such as publication bias, may have undermined the credibility of the pooled prevalence of hyperuricemia. Additionally, the inclusion of only two articles outside of Asia lead to fallacy in generalizing the finding to the wider world. The failure to standardize the varying definitions- for, for e.g., adolescent, cut point for hyperuricemia, and unit of measurement for hyperuricemia among the primary studies- may cast additional doubt over the credibility of the findings of this study.\\nDiscussion: The comparison of the findings of this synthesis with others went nicely. Nonetheless, the narrow scope of the analysis limited the discussion. Further, the way the authors discussed their findings lacks novelty. The limitations mentioned in the previous sections also contributed to the limitations in this section. The result does not substantiate some of the concluding remarks.\\n\\n* Are the methods appropriate and well described?: **No**\\n* Does the work include the necessary controls?: **Yes**\\n* Are the conclusions drawn adequately supported by the data shown?: **No**\\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\\n* Quality of written English: **Needs some language corrections before being published**\\n* Declaration of competing interests: **I declare that I have no competing interests.**\\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\\n\"},{\"type\":\"reviewerAgreed\",\"content\":\"\",\"date\":\"2020-03-11T12:00:00+00:00\",\"index\":3,\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2020-03-09T12:00:00+00:00\",\"index\":1,\"fulltext\":\"Recommendation: Accept after minor essential revisions\\nForm responses:\\n---\\n\\nComments to Author:\\n---\\n* Are the methods appropriate and well described?: **Yes**\\n* Does the work include the necessary controls?: **Yes**\\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\\n* Quality of written English: **Acceptable**\\n* Declaration of competing interests: ****\\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). 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