Burden of Gastroesophageal reflux disease in China and Global from 1990 to 2021 with forecast to 2041: An analysis and comparison

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However, long-term trends in its burden across different regions and the relationship with socio-demographic development remain incompletely understood. Methods: We extracted data on GERD incidence, prevalence, and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2021 database for China and globally between 1990 and 2021. Age-standardized rates (ASRs) were analyzed using Joinpoint regression to estimate annual percentage changes. An autoregressive integrated moving average (ARIMA) model was applied to forecast trends through 2041. Correlations between GERD burden and the Socio-demographic Index (SDI) were evaluated using Pearson’s coefficients. Results: In 2021, China reported an age-standardized prevalence rate (ASPR) of 4,540.66, incidence rate (ASIR) of 1,844.31, and DALY rate (ASDR) of 35.12 per 100,000, all substantially lower than global values (ASPR: 9,838.6; ASIR: 3,881.86; ASDR: 75.56 per 100,000). From 1990 to 2021, China’s absolute GERD cases increased by 60.6% (prevalence) and 55.2% (incidence), driven mainly by aging and population growth, while global cases rose by over 80%. Joinpoint analysis revealed accelerated growth in China after 2010, and ARIMA projections estimate a 7–12% rise in global GERD ASRs by 2041, with the DALY gap between China and global levels widening. Globally, SDI was positively correlated with GERD ASRs, whereas these associations were weak and nonsignificant in China. Conclusion: GERD poses a growing public health challenge, with a stable yet substantial burden in China and a continuing global increase through 2041. These findings highlight the urgent need for age- and context-specific prevention, early detection, and multidisciplinary management strategies to mitigate the future health and economic impact of GERD. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal disorder characterized by troublesome symptoms or mucosal injury resulting from abnormal reflux of gastric contents into the esophagus [ 1 ]. Typical clinical manifestations include heartburn, acid reflux, and regurgitation. Extra-esophageal symptoms, such as chronic cough, asthma, dental erosion, and laryngitis, also significantly impact patients' quality of life [ 2 , 3 ]. GERD not only reduces patients' health-related quality of life but also leads to severe complications such as esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, contributing to substantial healthcare costs and socioeconomic burden globally [ 4 ]. Over the past three decades, the global prevalence of GERD has steadily increased, influenced by demographic transitions, lifestyle modifications, and socioeconomic development [ 5 ]. However, due to heterogeneity in symptom interpretation and data scarcity in some regions, accurately quantifying the global and regional burden of GERD has been challenging [ 6 ]. Comprehensive, standardized epidemiological assessments are crucial for developing effective prevention and management strategies for GERD, particularly in regions experiencing rapid demographic and socioeconomic changes. China, as the world's most populous country, presents unique epidemiological characteristics in GERD research due to its rapid socioeconomic transformation, aging population, and changing dietary and lifestyle patterns[ 7 ]. Recent studies have indicated a rising incidence and prevalence of GERD among Chinese populations, potentially linked to increasing obesity rates, urbanization, dietary shifts, and environmental factors [ 8 , 9 ]. Nevertheless, studies investigating GERD epidemiology in China have been inconsistent, highlighting methodological variations and regional disparities. Reliable and standardized epidemiological data, such as those provided by the Global Burden of Disease (GBD) studies, are essential for accurately assessing disease burden and temporal trends in China. Comparative analyses between China and global trends can identify region-specific risk factors and facilitate tailored preventive measures. Given the significant demographic and socioeconomic changes occurring in China and Global, an in-depth analysis of GERD's burden and trend is urgently needed to inform health policy planning and resource allocation. To date, no comprehensive analysis has been conducted on the incidence, prevalence, and disability-adjusted life years (DALYs) burden of GERD in China. Therefore, we utilized data from the Global Burden of Disease (GBD) 2021 study to provide a detailed assessment of temporal trends and age-specific distributions of the GERD burden in China from 1990 to 2021. Joinpoint regression analysis was applied to identify significant trend changes across specific periods[ 10 ]. Furthermore, an autoregressive integrated moving average (ARIMA) model was employed to forecast the burden of GERD from 2022 to 2041. Spearman correlation analysis was used to examine associations between age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized DALY rate (ASDR), and the Socio-Demographic Index (SDI) at both national and global levels. This study provides robust epidemiological evidence on the burden of GERD in China and offers valuable insights for informing future public health policies. Materials and Methods Data Sources We obtained data from the GBD 2021 database ( https://vizhub.healthdata.org/gbd-results/ ). This secondary dataset analysis incorporated publicly available GBD estimates. Specifically, we extracted: (1) annual age-specific data for GERD from 1990 to 2021 in China and globally, including the number of disability-adjusted life years (DALYs), crude rates, and age-standardized rates (ASRs), namely age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized DALY rate (ASDR), and the Socio-demographic Index (SDI); and (2) population data by age group for China and the world from 1990 to 2021. Data were accessed on July 14, 2025. As this study exclusively utilized publicly available datasets, ethical approval and informed consent Statistical Analysis Descriptive Analysis Descriptive analyses were performed to summarize and compare the disease burden of GERD in China and globally. Absolute numbers, age-standardized rates per 100,000 individuals, and percentage changes were presented. All data utilized in the descriptive analysis were subjected to statistical analysis utilizing R software (version 4.4.1), with a significance threshold set at p < 0.05. Joinpoint Regression Analysis Temporal trends in ASIR, ASPR, and ASDR from 1990 to 2021 were evaluated using joinpoint regression analysis. This method identifies statistically significant trend changes by fitting segmented linear regression models. Annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals (CIs) were calculated to quantify trends over time. The analyses were executed using Joinpoint software (version 4.9.1.0; National Cancer Institute, USA)[ 11 ]. ARIMA Forecasting To predict future trends of GERD burden from 2022 to 2041, autoregressive integrated moving average (ARIMA) modeling was conducted. ARIMA is effective for capturing temporal patterns and trends in longitudinal data. Historical age-standardized rates from 1990 to 2021 were used to fit the ARIMA models, forecasting future ASIR, ASPR, and ASDR. Model selection involved analyzing residuals for white noise properties and ensuring that model assumptions were satisfied. Forecast analyses were performed using R software (version 4.4.1). Correlation Analysis The correlation between SDI and GERD burden indicators (ASIR, ASPR, ASDR) was assessed using Spearman correlation analysis. SDI, a composite index reflecting a region’s socioeconomic status, combines indicators such as income per capita, educational attainment, and fertility rates. Statistical significance was set at p < 0.05, and visualization of the correlation results was executed using R software. Data Visualization Figures were generated using R software for intuitive graphical presentation of trends, comparisons, and predictions of GERD burden between China and the global average. Graphical outputs included trend plots, joinpoint regression graphs, ARIMA forecast curves, and correlation scatter plots. Results Temporal trends of GERD in China and globally from 1990 to 2021 In 2021, the ASPR, ASIR, and ASDR of GERD in China were 4,540.66, 1,844.31, and 35.12 per 100,000 population, respectively. Compared with 1990, these ASRs remained largely unchanged, with percentage changes (PC) of − 0.004% for ASPR, − 0.004% for ASIR, and − 0.004% for ASDR. However, in terms of absolute numbers, China reported approximately 81.3 million prevalent cases, 32.4 million incident cases, and 626,248 DALYs in 2021, reflecting increases of 60.6%, 55.2%, and 59.0%, respectively, compared with 1990 (Table 1) . Globally, the ASPR, ASIR, and ASDR of GERD in 2021 were 9,838.6, 3,881.86, and 75.56 per 100,000 population, respectively. Compared with 1990, these rates increased modestly, with PCs of 3.4% for ASPR, 3.8% for ASIR, and 3.5% for ASDR. In terms of absolute numbers, there were approximately 825.6 million prevalent cases, 324.1 million incident cases, and 6.3 million DALYs globally in 2021, representing increases of 83.5%, 80.1%, and 82.5%, respectively, from 1990. From 1990 to 2021, China exhibited a gradually increasing trajectory in ASPR, ASIR, and ASDR, with periods of minor fluctuation. As shown in Fig. 1, incidence and prevalence rates declined slightly in the early 2000s, followed by steady growth, with notable accelerations after approximately 2010 for incidence and 2012 for prevalence (Fig. 1A–B). DALYs remained relatively stable in the early years before increasing consistently in the subsequent decade (Fig. 1C) . In contrast, the global GERD burden increased more steadily, without evident turning points. Despite consistently lower ASRs in China compared with global averages, the relative growth rates over time were comparable. Disease burden by age group: China vs. global comparison (1990 vs. 2021) Figure 2 compares incident and prevalent cases, DALYs, and corresponding crude incidence (CIR), prevalence (CPR), and DALY (CDR) rates across age groups in China and globally in 1990 and 2021 (Table S2 ). Incident cases, prevalent cases, and DALYs exhibited a reverse U-shaped distribution, peaking in mid-to-older age groups before declining. In China, the CIR, CPR, and CDR increased progressively with age across all groups, whereas globally, these rates peaked in the 75–79-year group before decreasing in the oldest ages. In 2021, the highest number of prevalent cases in China was observed in the 55–59-year group (9,008,627 cases), whereas globally, the peak prevalence occurred in the 35–39-year group (88,273,155 cases). For rates per 100,000 population, China’s prevalence steadily increased with age, whereas the global prevalence rate peaked in the 75–79-year group. Similarly, incidence in China peaked in the 50–54-year group (3,571,882 cases), while globally, it peaked in the 35–39-year group (33,735,408 cases). The highest incidence rate per 100,000 in China was in the 95 + group, compared with the 70–74-year group globally. For DALYs, the largest absolute burden in China was recorded in the 50–54-year group (69,546 years), while globally, the 35–39-year group accounted for the greatest burden (688,643 years). In terms of rates, DALYs peaked in the 75–79-year group in China versus the 70–74-year group globally. Between 1990 and 2021, the prevalence, incidence, and DALY rates across all age groups in China remained largely stable, yet substantially lower than global levels. Using the 30–34-year group as a threshold, the number of incident cases, prevalent cases, and DALYs in 2021 were lower than in 1990 for individuals younger than 30–34 years, but higher for those aged ≥ 30–34 years. Globally, incident cases, prevalent cases, and DALYs increased markedly across all age groups. When examining crude rates, a divergent pattern emerged: using 50–54 years as a threshold, individuals younger than this group exhibited higher CIR, CPR, and CDR in 2021 compared with 1990, whereas those aged > 54 years showed lower rates in 2021. This reflects a shift toward a younger age distribution of the global GERD burden. Joinpoint regression analysis of GERD trends (1990–2021) Joinpoint regression revealed segmented trends in ASPR, ASIR, and ASDR in China and globally (Fig. 3, Table S3 –S4). ASPR: In China, ASPR decreased from 1990–1994 (APC = − 1.21%, p < 0.01), then increased slightly during 1994–2005 (APC = 0.06%, p < 0.05), followed by a decline in 2005–2010 (APC = − 1.59%, p < 0.01), and a subsequent rise during 2010–2015 (APC = 0.51%, p < 0.01) and 2015–2018 (APC = 0.37%, p < 0.01). The overall AAPC was 0% (95% CI: − 0.09 to 0.10). Globally, ASPR increased steadily (AAPC: 0.11%, 95% CI: 0.10–0.12). ASIR: In China, ASIR rose notably in 2010–2015 (APC = 0.49%, p < 0.05) and 2015–2018 (APC = 2.59%, p < 0.05), with an overall AAPC of 0% (95% CI: − 0.08 to 0.09), compared with a global AAPC of 0.12% (95% CI: 0.11–0.13). ASDR: ASDR in China increased significantly during 2015–2018 (APC = 2.84%, p < 0.05) and modestly thereafter (APC = 0.43%, p < 0.05), with an overall AAPC of 0% (95% CI: − 0.09 to 0.10). Globally, ASDR rose more gradually (AAPC: 0.11%, 95% CI: 0.10–0.13). China experienced greater short-term fluctuations and sharper post-2010 increases than the global average, possibly reflecting shifts in dietary habits, rising obesity prevalence, and expanded diagnostic access. ARIMA forecasting of GERD burden (2022–2041) An autoregressive integrated moving average (ARIMA) model was used to project GERD burden from 2022 to 2041 (Fig. 4, Table S5 ). Globally, by 2041, the ASIR, ASPR, and ASDR are projected to reach approximately 4,200, 10,500, and 85 per 100,000, representing increases of 7.9%, 6.4%, and 11.9%, respectively, compared with 2021. In China, these metrics are expected to remain relatively stable, reaching approximately 1,850, 4,600, and 35 per 100,000, respectively, with minimal changes from 2021. The gap between China and global levels is expected to persist and slightly widen, particularly for ASDR. Association between GERD burden and SDI We evaluated the association between SDI and GERD burden from 1990 to 2021 (Fig. 5, Table S6 ) .Globally, significant positive correlations were observed between SDI and ASIR (R = 0.574, p < 0.001) and ASDR (R = 0.394, p = 0.026). ASPR also showed a positive but nonsignificant correlation (R = 0.338, p = 0.059). In contrast, in China, the associations were weakly negative and nonsignificant (ASIR: R = − 0.207, p = 0.256; ASPR: R = − 0.107, p = 0.252; ASDR: R = − 0.195, p = 0.286). These findings suggest that while socioeconomic development is strongly associated with GERD burden globally, its impact in China appears attenuated, likely due to context-specific factors such as healthcare policies, cultural dietary patterns, and diagnostic practices. Discussion In this comprehensive analysis of the Global Burden of Disease 2021 dataset, we systematically assessed the long-term temporal, age-specific, and socio-demographic trends of gastroesophageal reflux disease (GERD) in China and globally from 1990 to 2021, with projections to 2041. We found that although the age-standardized incidence, prevalence, and DALY rates of GERD in China remained substantially lower than global averages, the absolute numbers of cases and DALYs increased markedly, particularly among individuals aged ≥ 30 years. Moreover, Joinpoint analysis revealed accelerated growth after 2010, and ARIMA forecasts suggest that global GERD burden will continue to rise, with a persistent and slightly widening gap between China and global levels, especially in disability-adjusted life years. Importantly, we observed significant positive correlations between socio-demographic development (SDI) and GERD burden globally, whereas in China, these associations were weak and nonsignificant, indicating a unique epidemiological trajectory potentially influenced by healthcare policies, cultural factors, and diagnostic practices. Our findings are largely consistent with and extend those of previous GBD-based studies. Mo et al. reported that from 1990 to 2021, the global numbers of GERD prevalence, incidence, and YLDs increased by 83.16%, 80.06%, and 82.46%, respectively, with modest rises in age-standardized rates (EAPCs: 0.076–0.097)[ 12 ]. Similarly, Du et al. observed that between 1990 and 2021, the global ASIR, ASPR, and YLD rates increased by 3.80%, 3.38%, and 3.49%, respectively, with the highest burdens recorded in Tropical Latin America and the lowest in East Asia[ 13 ]. These patterns align with our analysis, which shows that while China maintained significantly lower ASRs than the global average, its absolute number of prevalent and incident cases increased by 60.6% and 55.2% between 1990 and 2021, reflecting the impact of population growth and aging rather than an intrinsic rise in disease risk. Our results also corroborate the observations of Li et al[ 14 ]. and Zhang et al[ 15 ]., who reported that East Asia, including China, had the lowest age-standardized prevalence, incidence, and YLD rates globally in 2019, despite large increases in case numbers. Notably, our Joinpoint analysis adds new insight by identifying accelerated increases in GERD incidence and prevalence after 2010, suggesting that recent factors—such as dietary westernization, rising obesity prevalence, and improved diagnostic awareness—may have contributed to the observed upturn. Furthermore, our study advances prior work by incorporating projections to 2041, revealing a likely widening gap in disability-adjusted life years (DALYs) between China and global levels. Our age-stratified analysis revealed a distinct divergence between China and global patterns. Globally, GERD burden has shifted toward younger age groups, with increasing incidence and prevalence among individuals aged 30–39, consistent with large electronic health record studies showing the greatest rise in GERD diagnoses in this demographic[ 16 ]. This younger age shift is likely driven by rising obesity rates, dietary westernization, and declining Helicobacter pylori prevalence, as supported by meta-analyses showing strong associations between higher BMI and GERD risk[ 17 ]. In contrast, in China, the highest absolute burden remains concentrated in middle-aged and older groups (50–59 years for cases; 75–79 years for rates), consistent with our observed reverse U-shaped distribution. This reflects China's rapid aging trajectory [ 16 ], indicating that demographic factors, rather than rising disease risk, are the main drivers of burden increases. These patterns carry substantial epidemiological implications: the global younger age shift emphasizes the need for early preventive measures, while in China, age-specific screening and management for older adults are crucial. Our correlation analysis demonstrated a significant positive association between SDI and GERD burden at the global level, consistent with recent GBD-based studies that linked higher SDI with increased GERD risk, likely due to dietary transitions, obesity, and enhanced diagnosis (bmcgastroenterol.biomedcentral.com). In contrast, our study revealed weak, nonsignificant correlations between SDI and GERD rates in China, diverging from the global pattern. This suggests that China's rising SDI has not translated into proportionately higher GERD detection, potentially due to persistent healthcare disparities, particularly between urban and rural regions, and the offsetting effects of obesity and westernized diets. Historical underdiagnosis and late presentation may also explain these discrepancies. Collectively, these dynamics underscore that socioeconomic advancement alone does not guarantee proportional changes in GERD burden without targeted health policy interventions. Our ARIMA-based projections anticipate that by 2041, the global GERD burden will continue its upward trajectory, with age-standardized incidence, prevalence, and DALY rates increasing by an estimated 7–12% above 2021 levels, particularly in low- and middleSDI regions[18].In contrast, our forecast suggests that China’s GERD rates will remain relatively stable, with only modest increases projected through 2041. Nonetheless, due to China's large population and aging demographic, the absolute number of DALYs is likely to remain substantial, and the DALYs gap between China and global averages is expected to widen [12]. These projections underscore the urgency of implementing context-specific prevention and management strategies to mitigate future burden. To curb the rising GERD burden, multifaceted, evidence-based interventions are required. Lifestyle modifications—including weight reduction, low-fat diets, and avoidance of smoking/alcohol—have proven effective in reducing GERD risk[ 19 ].Targeted screening of high-risk groups (e.g., older adults, obese patients) can enable early detection and prevent complications [ 20 ]. Strengthening diagnostic capacity—through expanded endoscopy access and standardized protocols—remains essential, especially in underserved areas [ 21 ]. Moreover, multidisciplinary care and public health education have shown benefits in improving symptom control and disease awareness[ 22 ] (pubmed.ncbi.nlm.nih.gov/30348496). Our study benefits from several notable strengths. Leveraging the comprehensive Global Burden of Disease 2021 dataset, we present the most uptodate analysis of GERD trends, integrating Joinpoint regression, ARIMA forecasting to 2041, and SDI correlation, thus providing a multidimensional understanding of GERD burden. However, some limitations must be acknowledged. First, GBD estimates rely on modeled data from heterogeneous sources, and in settings with limited direct surveillance, modeling may introduce uncertainty. Second, diagnostic criteria and healthcare access vary across countries and over time, potentially biasing trend estimates. Third, we did not account for individual-level behavioral and metabolic risk factors, limiting causal inference. Finally, our forecasts are contingent on past trends remaining stable, and unforeseen changes in healthcare policy or population behavior may alter future trajectories. Conclusion In summary, this study provides the most uptodate and comprehensive assessment of GERD burden in China and globally, revealing that China maintains substantially lower age-standardized rates than the global average, yet faces a marked rise in absolute cases and DALYs, particularly among middleaged and older adults. Global projections indicate a continued increase in GERD burden through 2041, with a widening gap in disabilityadjusted life years between China and the world. These findings underscore the urgent need for age and contextspecific prevention, early detection, and management strategies to mitigate the growing health and economic impact of GERD, especially in aging populations and sociodemographically transitioning regions. Declarations Author Contribution [Guodong Yang]: Conceptualization, data acquisition, statistical analysis, manuscript drafting, and critical revision.[Yujiao Zhang]: Data interpretation, literature review, and manuscript drafting.[Guodong Yang and Yujiao Zhang]: Statistical modeling (Joinpoint, ARIMA), figure preparation, and critical review.[Qibin Wu]: Methodology supervision, interpretation of results, and critical manuscript revision.All authors: Approved the final version of the manuscript and agree to be accountable for all aspects of the work. 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Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx TableS1.xlsx TableS2.xlsx TableS3.xlsx TableS4.xlsx TableS5.xlsx TableS6.xlsx 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7227485","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491757698,"identity":"1ab64f4d-5d61-402a-986d-5d828a518408","order_by":0,"name":"Guodong 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10:22:24","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":11342,"visible":true,"origin":"","legend":"","description":"","filename":"TableS4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7227485/v1/def65c8739928792674742f9.xlsx"},{"id":87817239,"identity":"6dc59302-4493-48fa-a436-7451638d70f0","added_by":"auto","created_at":"2025-07-29 10:22:24","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":20449,"visible":true,"origin":"","legend":"","description":"","filename":"TableS5.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7227485/v1/008aa5918e89f742b989c0c8.xlsx"},{"id":87817240,"identity":"f9d3f3fc-4093-477d-887d-71935413aa66","added_by":"auto","created_at":"2025-07-29 10:22:24","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":15780,"visible":true,"origin":"","legend":"","description":"","filename":"TableS6.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7227485/v1/cbb2b15a1073ff975a5563e6.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Burden of Gastroesophageal reflux disease in China and Global from 1990 to 2021 with forecast to 2041: An analysis and comparison","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGastroesophageal reflux disease (GERD) is a chronic gastrointestinal disorder characterized by troublesome symptoms or mucosal injury resulting from abnormal reflux of gastric contents into the esophagus [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Typical clinical manifestations include heartburn, acid reflux, and regurgitation. Extra-esophageal symptoms, such as chronic cough, asthma, dental erosion, and laryngitis, also significantly impact patients' quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. GERD not only reduces patients' health-related quality of life but also leads to severe complications such as esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, contributing to substantial healthcare costs and socioeconomic burden globally [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Over the past three decades, the global prevalence of GERD has steadily increased, influenced by demographic transitions, lifestyle modifications, and socioeconomic development [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, due to heterogeneity in symptom interpretation and data scarcity in some regions, accurately quantifying the global and regional burden of GERD has been challenging [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Comprehensive, standardized epidemiological assessments are crucial for developing effective prevention and management strategies for GERD, particularly in regions experiencing rapid demographic and socioeconomic changes.\u003c/p\u003e\u003cp\u003eChina, as the world's most populous country, presents unique epidemiological characteristics in GERD research due to its rapid socioeconomic transformation, aging population, and changing dietary and lifestyle patterns[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Recent studies have indicated a rising incidence and prevalence of GERD among Chinese populations, potentially linked to increasing obesity rates, urbanization, dietary shifts, and environmental factors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Nevertheless, studies investigating GERD epidemiology in China have been inconsistent, highlighting methodological variations and regional disparities. Reliable and standardized epidemiological data, such as those provided by the Global Burden of Disease (GBD) studies, are essential for accurately assessing disease burden and temporal trends in China. Comparative analyses between China and global trends can identify region-specific risk factors and facilitate tailored preventive measures. Given the significant demographic and socioeconomic changes occurring in China and Global, an in-depth analysis of GERD's burden and trend is urgently needed to inform health policy planning and resource allocation.\u003c/p\u003e\u003cp\u003eTo date, no comprehensive analysis has been conducted on the incidence, prevalence, and disability-adjusted life years (DALYs) burden of GERD in China. Therefore, we utilized data from the Global Burden of Disease (GBD) 2021 study to provide a detailed assessment of temporal trends and age-specific distributions of the GERD burden in China from 1990 to 2021. Joinpoint regression analysis was applied to identify significant trend changes across specific periods[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Furthermore, an autoregressive integrated moving average (ARIMA) model was employed to forecast the burden of GERD from 2022 to 2041. Spearman correlation analysis was used to examine associations between age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized DALY rate (ASDR), and the Socio-Demographic Index (SDI) at both national and global levels. This study provides robust epidemiological evidence on the burden of GERD in China and offers valuable insights for informing future public health policies.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cb\u003eData Sources\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe obtained data from the GBD 2021 database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://vizhub.healthdata.org/gbd-results/\u003c/span\u003e\u003cspan address=\"https://vizhub.healthdata.org/gbd-results/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). This secondary dataset analysis incorporated publicly available GBD estimates. Specifically, we extracted: (1) annual age-specific data for GERD from 1990 to 2021 in China and globally, including the number of disability-adjusted life years (DALYs), crude rates, and age-standardized rates (ASRs), namely age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized DALY rate (ASDR), and the Socio-demographic Index (SDI); and (2) population data by age group for China and the world from 1990 to 2021. Data were accessed on July 14, 2025. As this study exclusively utilized publicly available datasets, ethical approval and informed consent\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eDescriptive Analysis\u003c/p\u003e\u003cp\u003eDescriptive analyses were performed to summarize and compare the disease burden of GERD in China and globally. Absolute numbers, age-standardized rates per 100,000 individuals, and percentage changes were presented. All data utilized in the descriptive analysis were subjected to statistical analysis utilizing R software (version 4.4.1), with a significance threshold set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eJoinpoint Regression Analysis\u003c/p\u003e\u003cp\u003eTemporal trends in ASIR, ASPR, and ASDR from 1990 to 2021 were evaluated using joinpoint regression analysis. This method identifies statistically significant trend changes by fitting segmented linear regression models. Annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals (CIs) were calculated to quantify trends over time. The analyses were executed using Joinpoint software (version 4.9.1.0; National Cancer Institute, USA)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eARIMA Forecasting\u003c/p\u003e\u003cp\u003eTo predict future trends of GERD burden from 2022 to 2041, autoregressive integrated moving average (ARIMA) modeling was conducted. ARIMA is effective for capturing temporal patterns and trends in longitudinal data. Historical age-standardized rates from 1990 to 2021 were used to fit the ARIMA models, forecasting future ASIR, ASPR, and ASDR. Model selection involved analyzing residuals for white noise properties and ensuring that model assumptions were satisfied. Forecast analyses were performed using R software (version 4.4.1).\u003c/p\u003e\u003cp\u003eCorrelation Analysis\u003c/p\u003e\u003cp\u003eThe correlation between SDI and GERD burden indicators (ASIR, ASPR, ASDR) was assessed using Spearman correlation analysis. SDI, a composite index reflecting a region\u0026rsquo;s socioeconomic status, combines indicators such as income per capita, educational attainment, and fertility rates. Statistical significance was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, and visualization of the correlation results was executed using R software.\u003c/p\u003e\u003cp\u003eData Visualization\u003c/p\u003e\u003cp\u003eFigures were generated using R software for intuitive graphical presentation of trends, comparisons, and predictions of GERD burden between China and the global average. Graphical outputs included trend plots, joinpoint regression graphs, ARIMA forecast curves, and correlation scatter plots.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eTemporal trends of GERD in China and globally from 1990 to 2021\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn 2021, the ASPR, ASIR, and ASDR of GERD in China were 4,540.66, 1,844.31, and 35.12 per 100,000 population, respectively. Compared with 1990, these ASRs remained largely unchanged, with percentage changes (PC) of \u0026minus;\u0026thinsp;0.004% for ASPR, \u0026minus;\u0026thinsp;0.004% for ASIR, and \u0026minus;\u0026thinsp;0.004% for ASDR. However, in terms of absolute numbers, China reported approximately 81.3\u0026nbsp;million prevalent cases, 32.4\u0026nbsp;million incident cases, and 626,248 DALYs in 2021, reflecting increases of 60.6%, 55.2%, and 59.0%, respectively, compared with 1990 \u003cb\u003e(Table\u0026nbsp;1)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eGlobally, the ASPR, ASIR, and ASDR of GERD in 2021 were 9,838.6, 3,881.86, and 75.56 per 100,000 population, respectively. Compared with 1990, these rates increased modestly, with PCs of 3.4% for ASPR, 3.8% for ASIR, and 3.5% for ASDR. In terms of absolute numbers, there were approximately 825.6\u0026nbsp;million prevalent cases, 324.1\u0026nbsp;million incident cases, and 6.3\u0026nbsp;million DALYs globally in 2021, representing increases of 83.5%, 80.1%, and 82.5%, respectively, from 1990.\u003c/p\u003e\u003cp\u003eFrom 1990 to 2021, China exhibited a gradually increasing trajectory in ASPR, ASIR, and ASDR, with periods of minor fluctuation. As shown in Fig.\u0026nbsp;1, incidence and prevalence rates declined slightly in the early 2000s, followed by steady growth, with notable accelerations after approximately 2010 for incidence and 2012 for prevalence \u003cb\u003e(Fig.\u0026nbsp;1A\u0026ndash;B).\u003c/b\u003e DALYs remained relatively stable in the early years before increasing consistently in the subsequent decade \u003cb\u003e(Fig.\u0026nbsp;1C)\u003c/b\u003e. In contrast, the global GERD burden increased more steadily, without evident turning points. Despite consistently lower ASRs in China compared with global averages, the relative growth rates over time were comparable.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDisease burden by age group: China vs. global comparison (1990 vs. 2021)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFigure 2 compares incident and prevalent cases, DALYs, and corresponding crude incidence (CIR), prevalence (CPR), and DALY (CDR) rates across age groups in China and globally in 1990 and 2021 \u003cb\u003e(Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIncident cases, prevalent cases, and DALYs exhibited a reverse U-shaped distribution, peaking in mid-to-older age groups before declining. In China, the CIR, CPR, and CDR increased progressively with age across all groups, whereas globally, these rates peaked in the 75\u0026ndash;79-year group before decreasing in the oldest ages.\u003c/p\u003e\u003cp\u003eIn 2021, the highest number of prevalent cases in China was observed in the 55\u0026ndash;59-year group (9,008,627 cases), whereas globally, the peak prevalence occurred in the 35\u0026ndash;39-year group (88,273,155 cases). For rates per 100,000 population, China\u0026rsquo;s prevalence steadily increased with age, whereas the global prevalence rate peaked in the 75\u0026ndash;79-year group. Similarly, incidence in China peaked in the 50\u0026ndash;54-year group (3,571,882 cases), while globally, it peaked in the 35\u0026ndash;39-year group (33,735,408 cases). The highest incidence rate per 100,000 in China was in the 95\u0026thinsp;+\u0026thinsp;group, compared with the 70\u0026ndash;74-year group globally. For DALYs, the largest absolute burden in China was recorded in the 50\u0026ndash;54-year group (69,546 years), while globally, the 35\u0026ndash;39-year group accounted for the greatest burden (688,643 years). In terms of rates, DALYs peaked in the 75\u0026ndash;79-year group in China versus the 70\u0026ndash;74-year group globally.\u003c/p\u003e\u003cp\u003eBetween 1990 and 2021, the prevalence, incidence, and DALY rates across all age groups in China remained largely stable, yet substantially lower than global levels. Using the 30\u0026ndash;34-year group as a threshold, the number of incident cases, prevalent cases, and DALYs in 2021 were lower than in 1990 for individuals younger than 30\u0026ndash;34 years, but higher for those aged\u0026thinsp;\u0026ge;\u0026thinsp;30\u0026ndash;34 years. Globally, incident cases, prevalent cases, and DALYs increased markedly across all age groups. When examining crude rates, a divergent pattern emerged: using 50\u0026ndash;54 years as a threshold, individuals younger than this group exhibited higher CIR, CPR, and CDR in 2021 compared with 1990, whereas those aged\u0026thinsp;\u0026gt;\u0026thinsp;54 years showed lower rates in 2021. This reflects a shift toward a younger age distribution of the global GERD burden.\u003c/p\u003e\u003cp\u003e\u003cb\u003eJoinpoint regression analysis of GERD trends (1990\u0026ndash;2021)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eJoinpoint regression revealed segmented trends in ASPR, ASIR, and ASDR in China and globally \u003cb\u003e(Fig.\u0026nbsp;3, Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e\u0026ndash;S4).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eASPR: In China, ASPR decreased from 1990\u0026ndash;1994 (APC = \u0026minus;\u0026thinsp;1.21%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), then increased slightly during 1994\u0026ndash;2005 (APC\u0026thinsp;=\u0026thinsp;0.06%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), followed by a decline in 2005\u0026ndash;2010 (APC = \u0026minus;\u0026thinsp;1.59%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and a subsequent rise during 2010\u0026ndash;2015 (APC\u0026thinsp;=\u0026thinsp;0.51%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and 2015\u0026ndash;2018 (APC\u0026thinsp;=\u0026thinsp;0.37%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The overall AAPC was 0% (95% CI: \u0026minus;\u0026thinsp;0.09 to 0.10). Globally, ASPR increased steadily (AAPC: 0.11%, 95% CI: 0.10\u0026ndash;0.12).\u003c/p\u003e\u003cp\u003eASIR: In China, ASIR rose notably in 2010\u0026ndash;2015 (APC\u0026thinsp;=\u0026thinsp;0.49%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and 2015\u0026ndash;2018 (APC\u0026thinsp;=\u0026thinsp;2.59%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with an overall AAPC of 0% (95% CI: \u0026minus;\u0026thinsp;0.08 to 0.09), compared with a global AAPC of 0.12% (95% CI: 0.11\u0026ndash;0.13).\u003c/p\u003e\u003cp\u003eASDR: ASDR in China increased significantly during 2015\u0026ndash;2018 (APC\u0026thinsp;=\u0026thinsp;2.84%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and modestly thereafter (APC\u0026thinsp;=\u0026thinsp;0.43%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with an overall AAPC of 0% (95% CI: \u0026minus;\u0026thinsp;0.09 to 0.10). Globally, ASDR rose more gradually (AAPC: 0.11%, 95% CI: 0.10\u0026ndash;0.13).\u003c/p\u003e\u003cp\u003eChina experienced greater short-term fluctuations and sharper post-2010 increases than the global average, possibly reflecting shifts in dietary habits, rising obesity prevalence, and expanded diagnostic access.\u003c/p\u003e\u003cp\u003e\u003cb\u003eARIMA forecasting of GERD burden (2022\u0026ndash;2041)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAn autoregressive integrated moving average (ARIMA) model was used to project GERD burden from 2022 to 2041 \u003cb\u003e(Fig.\u0026nbsp;4, Table \u003cspan refid=\"MOESM5\" class=\"InternalRef\"\u003eS5\u003c/span\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eGlobally, by 2041, the ASIR, ASPR, and ASDR are projected to reach approximately 4,200, 10,500, and 85 per 100,000, representing increases of 7.9%, 6.4%, and 11.9%, respectively, compared with 2021. In China, these metrics are expected to remain relatively stable, reaching approximately 1,850, 4,600, and 35 per 100,000, respectively, with minimal changes from 2021. The gap between China and global levels is expected to persist and slightly widen, particularly for ASDR.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAssociation between GERD burden and SDI\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe evaluated the association between SDI and GERD burden from 1990 to 2021 \u003cb\u003e(Fig.\u0026nbsp;5, Table \u003cspan refid=\"MOESM6\" class=\"InternalRef\"\u003eS6\u003c/span\u003e)\u003c/b\u003e.Globally, significant positive correlations were observed between SDI and ASIR (R\u0026thinsp;=\u0026thinsp;0.574, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and ASDR (R\u0026thinsp;=\u0026thinsp;0.394, p\u0026thinsp;=\u0026thinsp;0.026). ASPR also showed a positive but nonsignificant correlation (R\u0026thinsp;=\u0026thinsp;0.338, p\u0026thinsp;=\u0026thinsp;0.059). In contrast, in China, the associations were weakly negative and nonsignificant (ASIR: R = \u0026minus;\u0026thinsp;0.207, p\u0026thinsp;=\u0026thinsp;0.256; ASPR: R = \u0026minus;\u0026thinsp;0.107, p\u0026thinsp;=\u0026thinsp;0.252; ASDR: R = \u0026minus;\u0026thinsp;0.195, p\u0026thinsp;=\u0026thinsp;0.286). These findings suggest that while socioeconomic development is strongly associated with GERD burden globally, its impact in China appears attenuated, likely due to context-specific factors such as healthcare policies, cultural dietary patterns, and diagnostic practices.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this comprehensive analysis of the Global Burden of Disease 2021 dataset, we systematically assessed the long-term temporal, age-specific, and socio-demographic trends of gastroesophageal reflux disease (GERD) in China and globally from 1990 to 2021, with projections to 2041. We found that although the age-standardized incidence, prevalence, and DALY rates of GERD in China remained substantially lower than global averages, the absolute numbers of cases and DALYs increased markedly, particularly among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;30 years. Moreover, Joinpoint analysis revealed accelerated growth after 2010, and ARIMA forecasts suggest that global GERD burden will continue to rise, with a persistent and slightly widening gap between China and global levels, especially in disability-adjusted life years. Importantly, we observed significant positive correlations between socio-demographic development (SDI) and GERD burden globally, whereas in China, these associations were weak and nonsignificant, indicating a unique epidemiological trajectory potentially influenced by healthcare policies, cultural factors, and diagnostic practices.\u003c/p\u003e\u003cp\u003eOur findings are largely consistent with and extend those of previous GBD-based studies. Mo et al. reported that from 1990 to 2021, the global numbers of GERD prevalence, incidence, and YLDs increased by 83.16%, 80.06%, and 82.46%, respectively, with modest rises in age-standardized rates (EAPCs: 0.076\u0026ndash;0.097)[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Similarly, Du et al. observed that between 1990 and 2021, the global ASIR, ASPR, and YLD rates increased by 3.80%, 3.38%, and 3.49%, respectively, with the highest burdens recorded in Tropical Latin America and the lowest in East Asia[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These patterns align with our analysis, which shows that while China maintained significantly lower ASRs than the global average, its absolute number of prevalent and incident cases increased by 60.6% and 55.2% between 1990 and 2021, reflecting the impact of population growth and aging rather than an intrinsic rise in disease risk. Our results also corroborate the observations of Li et al[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. and Zhang et al[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]., who reported that East Asia, including China, had the lowest age-standardized prevalence, incidence, and YLD rates globally in 2019, despite large increases in case numbers. Notably, our Joinpoint analysis adds new insight by identifying accelerated increases in GERD incidence and prevalence after 2010, suggesting that recent factors\u0026mdash;such as dietary westernization, rising obesity prevalence, and improved diagnostic awareness\u0026mdash;may have contributed to the observed upturn. Furthermore, our study advances prior work by incorporating projections to 2041, revealing a likely widening gap in disability-adjusted life years (DALYs) between China and global levels.\u003c/p\u003e\u003cp\u003eOur age-stratified analysis revealed a distinct divergence between China and global patterns. Globally, GERD burden has shifted toward younger age groups, with increasing incidence and prevalence among individuals aged 30\u0026ndash;39, consistent with large electronic health record studies showing the greatest rise in GERD diagnoses in this demographic[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This younger age shift is likely driven by rising obesity rates, dietary westernization, and declining Helicobacter pylori prevalence, as supported by meta-analyses showing strong associations between higher BMI and GERD risk[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, in China, the highest absolute burden remains concentrated in middle-aged and older groups (50\u0026ndash;59 years for cases; 75\u0026ndash;79 years for rates), consistent with our observed reverse U-shaped distribution. This reflects China's rapid aging trajectory [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], indicating that demographic factors, rather than rising disease risk, are the main drivers of burden increases. These patterns carry substantial epidemiological implications: the global younger age shift emphasizes the need for early preventive measures, while in China, age-specific screening and management for older adults are crucial.\u003c/p\u003e\u003cp\u003eOur correlation analysis demonstrated a significant positive association between SDI and GERD burden at the global level, consistent with recent GBD-based studies that linked higher SDI with increased GERD risk, likely due to dietary transitions, obesity, and enhanced diagnosis (bmcgastroenterol.biomedcentral.com). In contrast, our study revealed weak, nonsignificant correlations between SDI and GERD rates in China, diverging from the global pattern. This suggests that China's rising SDI has not translated into proportionately higher GERD detection, potentially due to persistent healthcare disparities, particularly between urban and rural regions, and the offsetting effects of obesity and westernized diets. Historical underdiagnosis and late presentation may also explain these discrepancies. Collectively, these dynamics underscore that socioeconomic advancement alone does not guarantee proportional changes in GERD burden without targeted health policy interventions.\u003c/p\u003e\u003cp\u003eOur ARIMA-based projections anticipate that by 2041, the global GERD burden will continue its upward trajectory, with age-standardized incidence, prevalence, and DALY rates increasing by an estimated 7\u0026ndash;12% above 2021 levels, particularly in low- and middleSDI regions[18].In contrast, our forecast suggests that China\u0026rsquo;s GERD rates will remain relatively stable, with only modest increases projected through 2041. Nonetheless, due to China's large population and aging demographic, the absolute number of DALYs is likely to remain substantial, and the DALYs gap between China and global averages is expected to widen [12]. These projections underscore the urgency of implementing context-specific prevention and management strategies to mitigate future burden.\u003c/p\u003e\u003cp\u003eTo curb the rising GERD burden, multifaceted, evidence-based interventions are required. Lifestyle modifications\u0026mdash;including weight reduction, low-fat diets, and avoidance of smoking/alcohol\u0026mdash;have proven effective in reducing GERD risk[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].Targeted screening of high-risk groups (e.g., older adults, obese patients) can enable early detection and prevent complications [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Strengthening diagnostic capacity\u0026mdash;through expanded endoscopy access and standardized protocols\u0026mdash;remains essential, especially in underserved areas [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, multidisciplinary care and public health education have shown benefits in improving symptom control and disease awareness[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] (pubmed.ncbi.nlm.nih.gov/30348496).\u003c/p\u003e\u003cp\u003eOur study benefits from several notable strengths. Leveraging the comprehensive Global Burden of Disease 2021 dataset, we present the most uptodate analysis of GERD trends, integrating Joinpoint regression, ARIMA forecasting to 2041, and SDI correlation, thus providing a multidimensional understanding of GERD burden. However, some limitations must be acknowledged. First, GBD estimates rely on modeled data from heterogeneous sources, and in settings with limited direct surveillance, modeling may introduce uncertainty. Second, diagnostic criteria and healthcare access vary across countries and over time, potentially biasing trend estimates. Third, we did not account for individual-level behavioral and metabolic risk factors, limiting causal inference. Finally, our forecasts are contingent on past trends remaining stable, and unforeseen changes in healthcare policy or population behavior may alter future trajectories.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study provides the most uptodate and comprehensive assessment of GERD burden in China and globally, revealing that China maintains substantially lower age-standardized rates than the global average, yet faces a marked rise in absolute cases and DALYs, particularly among middleaged and older adults. Global projections indicate a continued increase in GERD burden through 2041, with a widening gap in disabilityadjusted life years between China and the world. These findings underscore the urgent need for age and contextspecific prevention, early detection, and management strategies to mitigate the growing health and economic impact of GERD, especially in aging populations and sociodemographically transitioning regions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e[Guodong Yang]: Conceptualization, data acquisition, statistical analysis, manuscript drafting, and critical revision.[Yujiao Zhang]: Data interpretation, literature review, and manuscript drafting.[Guodong Yang and Yujiao Zhang]: Statistical modeling (Joinpoint, ARIMA), figure preparation, and critical review.[Qibin Wu]: Methodology supervision, interpretation of results, and critical manuscript revision.All authors: Approved the final version of the manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTanvir F, et al. Gastroesophageal Reflux Disease: New Insights and Treatment Approaches. Cureus. 2024;16(8):e67654.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e\u003cem\u003e[Shanghai consensus on the diagnosis and treatment of gastroesophageal reflux disease in patients undergoing sleeve gastrectomy(2024 edition)].\u003c/em\u003e Zhonghua Wei Chang Wai Ke Za Zhi, 2024. 27(9): pp. 863\u0026ndash;878.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePoelmans J, Tack J. Extraoesophageal manifestations of gastro-oesophageal reflux. Gut. 2005;54(10):1492\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhieu M, Mukherjee S. \u003cem\u003eBarrett Esophagus\u003c/em\u003e, in \u003cem\u003eStatPearls\u003c/em\u003e. 2024, StatPearls Publishing Copyright \u0026copy; 2024, StatPearls Publishing LLC.: Treasure Island (FL) ineligible companies. Disclosure: Sandeep Mukherjee declares no relevant financial relationships with ineligible companies.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin Y, He J, Ding Z. Sedentary and 21 gastrointestinal disorders: A Mendelian randomization study. Med (Baltim). 2024;103(38):e39813.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHawkins EH. A tale of two systems: co-occurring mental health and substance abuse disorders treatment for adolescents. Annu Rev Psychol. 2009;60:197\u0026ndash;227.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu TL, et al. Meta-analysis on the epidemiology of gastroesophageal reflux disease in China. World J Gastroenterol. 2022;28(45):6410\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang D, et al. Global, regional and national burden of gastroesophageal reflux disease, 1990\u0026ndash;2019: update from the GBD 2019 study. Ann Med. 2022;54(1):1372\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi N, et al. Burden of gastroesophageal reflux disease in 204 countries and territories, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of disease study 2019. BMC Public Health. 2023;23(1):582.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIsnar S, Oremus M. Examining the association between the COVID-19 pandemic and self-harm death counts in four Canadian provinces. Psychiatry Res. 2022;310:114433.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim HJ, et al. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMo L, et al. Global, regional, and national burden of gastroesophageal reflux disease (1990\u0026ndash;2021): age-period-cohort analysis and Bayesian projections. Front Public Health. 2025;13:1576527.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDu L et al. \u003cem\u003eThe Global, Regional and National Burden of Gastroesophageal Reflux Disease in 204 Countries and Territories, 1990\u0026ndash;2021 a Retrospective Cohort Study.\u003c/em\u003e 2025: p. 10.1097.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi N et al. Burden of gastroesophageal reflux disease in 204 countries and territories, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of disease study 2019. 2023. 23(1): p. 582.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang D et al. Global, regional and national burden of gastroesophageal reflux disease, 1990\u0026ndash;2019: update from the GBD 2019 study. 2022. 54(1): pp. 1372\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamasaki T, et al. The Changing Epidemiology of Gastroesophageal Reflux Disease: Are Patients Getting Younger? J Neurogastroenterol Motil. 2018;24(4):559\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXie M et al. Obesity is associated with higher prevalence of gastroesophageal reflux disease and reflux related complications: a global healthcare database study. 2024. 36(4): p. e14750.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBai Z et al. \u003cem\u003eThe global, regional, and national patterns of change in the burden of nonmalignant upper gastrointestinal diseases from 1990 to 2019 and the forecast for the next decade.\u003c/em\u003e 2025. 111(1): pp. 80\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eManning KJ, Chan G, Steffens DC. Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression. Am J Geriatr Psychiatry. 2017;25(3):220\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrehm E, et al. Prenatal Exposure to Di(2-Ethylhexyl) Phthalate Causes Long-Term Transgenerational Effects on Female Reproduction in Mice. Endocrinology. 2018;159(2):795\u0026ndash;809.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eErol B, et al. Reconstruction of advanced periacetabular metastatic lesions with modified Harrington procedure. Acta Orthop Traumatol Turc. 2016;50(2):178\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTal E, et al. Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype. DNA Repair (Amst). 2018;72:10\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"[email protected]","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":"","lastPublishedDoi":"10.21203/rs.3.rs-7227485/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7227485/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cbr\u003e\nGastroesophageal reflux disease (GERD) is a major cause of gastrointestinal morbidity worldwide. However, long-term trends in its burden across different regions and the relationship with socio-demographic development remain incompletely understood.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nWe extracted data on GERD incidence, prevalence, and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2021 database for China and globally between 1990 and 2021. Age-standardized rates (ASRs) were analyzed using Joinpoint regression to estimate annual percentage changes. An autoregressive integrated moving average (ARIMA) model was applied to forecast trends through 2041. Correlations between GERD burden and the Socio-demographic Index (SDI) were evaluated using Pearson’s coefficients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nIn 2021, China reported an age-standardized prevalence rate (ASPR) of 4,540.66, incidence rate (ASIR) of 1,844.31, and DALY rate (ASDR) of 35.12 per 100,000, all substantially lower than global values (ASPR: 9,838.6; ASIR: 3,881.86; ASDR: 75.56 per 100,000). From 1990 to 2021, China’s absolute GERD cases increased by 60.6% (prevalence) and 55.2% (incidence), driven mainly by aging and population growth, while global cases rose by over 80%. Joinpoint analysis revealed accelerated growth in China after 2010, and ARIMA projections estimate a 7–12% rise in global GERD ASRs by 2041, with the DALY gap between China and global levels widening. Globally, SDI was positively correlated with GERD ASRs, whereas these associations were weak and nonsignificant in China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nGERD poses a growing public health challenge, with a stable yet substantial burden in China and a continuing global increase through 2041. These findings highlight the urgent need for age- and context-specific prevention, early detection, and multidisciplinary management strategies to mitigate the future health and economic impact of GERD.\u003c/p\u003e","manuscriptTitle":"Burden of Gastroesophageal reflux disease in China and Global from 1990 to 2021 with forecast to 2041: An analysis and comparison","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-29 10:22:19","doi":"10.21203/rs.3.rs-7227485/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"ab43202b-2a1c-4a4a-81d4-f62a476bb8de","owner":[],"postedDate":"July 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-29T06:39:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-29 10:22:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7227485","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7227485","identity":"rs-7227485","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}