Temporal trends in the disease burden of thalassemia in China from 1990 to 2021 and forecast to 2030

Temporal trends in the disease burden of thalassemia in China from 1990 to 2021 and forecast to 2030 | 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 Temporal trends in the disease burden of thalassemia in China from 1990 to 2021 and forecast to 2030 Xinan Pan, Xinyi Bai, Shilong Gu, Wenyan Wang, Linzhu Tian, Ke Huang, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7350201/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background China accounts for the highest number of newly diagnosed thalassemia cases globally and harbors the largest population of thalassemia patients. However, its burden and disparities remain insufficiently characterized. To guide resource allocation and prevention strategies, this study analyzed the distribution and trends of thalassemia burden in China from 1990 to 2021. Methods We utilized data from the Global Burden of Disease (GBD) Study 2021 to assess the burden of thalassemia in China. This analysis involved estimating the absolute numbers and corresponding age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Additionally, we employed the autoregressive integrated moving average (ARIMA) model to forecast trends through 2030. Results In 2021, China recorded the highest number of incident cases worldwide, with 40,143.5 cases (95% UI: 29,325.4–54,927.5), and its age-standardized incidence rate (ASIR) was 7.6 (95% UI: 5.5–10.4) per 100,000 population. From 1990 to 2021, both the ASIR and age-standardized mortality rate (ASMR) of thalassemia in China declined, with estimated annual percentage changes (EAPCs) of -0.60 (95% CI: -0.71 to -0.48) and − 4.90 (95% CI: -5.06 to -4.73), respectively. In 2021, the ASIR, age-standardized prevalence rate (ASPR), ASMR, and age-standardized DALYs rate (ASDR) of thalassemia in China were higher in males than females, and the incidence, prevalence, mortality, and DALY rates peaked in the < 5 age group for both sexes. Projections for the next 9 years indicate a steady decline in the ASMR and ASDR; however, the ASIR and ASPR are expected to rise further. Conclusions Thalassemia represents a major public health challenge in China, with a persistently high disease burden. A pressing need exists to raise public awareness of the risk factors associated with thalassemia and to implement effective preventive strategies to reduce the future burden of this disorder. Thalassemia Global burden of disease China Joinpoint regression analysis Epidemiological study Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1 Background Thalassemia, a group of monogenic disorders caused by mutations in α- or β-globin genes, is classified into α-thalassemia and β-thalassemia based on the affected globin chain[ 1 ].An imbalance between α- and β-globin chain production leads to ineffective erythropoiesis and chronic hemolysis, which underlies the disease pathophysiology. In α-thalassemia major, reduced synthesis of α-globin chains results in an imbalance of the α- and β-globin, causing hypoproteinemia and cardiac insufficiency; most affected individuals succumb either in the late gestational period or shortly after birth[ 2 – 4 ]. In β-thalassemia major, defective β-globin synthesis results in severe anemia, requiring lifelong transfusion dependence and leading to complications such as iron overload–induced cardiac and hepatic damage[ 3 , 5 , 6 ]. As an incurable condition, thalassemia requires lifelong multidisciplinary management to address chronic iron overload, multisystem complications, and the increased risk of malignancy[ 1 ]. Globally, thalassemia displays pronounced geographical heterogeneity, with high-prevalence regions (> 5%) predominantly located in historically malaria-endemic areas of Asia, the Middle East, and the Mediterranean, while prevalence remains low (< 0.1%) in Europe and North America[ 7 ]. A primary driver underlying these distribution patterns is the overlap between historical malaria-endemic areas (particularly Plasmodium falciparum ) and thalassemia hotspots. Heterozygous carriers of thalassemia mutations experience a survival advantage in malaria-endemic regions due to red blood cell abnormalities that inhibit plasmodial parasitism, thereby promoting natural selection and the genetic dissemination of thalassemia mutations[ 8 ]. The distribution of thalassemia may also be influenced by multiple factors, including genetic evolution, environmental pressures, population migration, and healthcare availability. Consequently, due to these geographical, genetic, and demographic factors, including the large population in China, the country now bears the highest global burden of thalassemia, with approximately 30 million individuals harboring thalassemia-related mutations[ 9 ]. In China, the overall prevalence of α-thalassemia, β-thalassemia, and combined α + β-thalassemia are 7.88%, 2.21%, and 0.48%, respectively[ 9 , 10 ]. Therefore, analyzing long-term trends and epidemiological characteristics of thalassemia in China is crucial for developing effective prevention and control strategies. Despite its significant public health impact, research on thalassemia in China remains limited. Leveraging standardized methodologies and epidemiological data, the Global Burden of Disease, Injuries, and Risk Factors Study 2021 (GBD 2021), which encompasses health statistics from 204 countries and territories, has expanded upon previous findings. Utilizing GBD 2021 data, this study systematically analyzes temporal trends in thalassemia in China from 1990 to 2021, focusing on key indicators such as incidence, prevalence, mortality, disability-adjusted life years (DALYs), the socio-demographic index (SDI), and average percentage change (APC). The objective of this study is to assess the most recent advancements in the epidemiology of thalassemia, address existing knowledge gaps, and guide the development of health policies and resource allocation strategies. 2 Methods 2.1 Overview The GBD 2021 estimated the health loss due to 371 diseases and injuries using 100,983 data sources from 204 countries and territories. The original data were collected from disease-specific registries, health service contact data, vital registration systems, censuses, household surveys, and other sources[ 11 ]. The dataset utilized in this analysis is publicly accessible through the GHDx query tool at https://vizhub.healthdata.org/gbd-results/ . The principal methods for estimating incidence, prevalence, mortality, and DALYs by age, sex, year, and location in GBD 2021 included the Cause of Death Ensemble model (CODEm), Spatiotemporal Gaussian process regression (ST-GPR), and the Bayesian meta-regression tool DisMod-MR. 2.2 Disease burden indicators We extracted disease burden metrics with 95% uncertainty intervals (UIs), including absolute numbers and age-standardized rates (ASRs) per 100,000 population for incidence, prevalence, mortality, and disability-adjusted life years (DALYs), referred to as the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Furthermore, we calculated the estimated annual percentage change (EAPC) to evaluate temporal trends in the burden of thalassemia from 1990 to 2021. The EAPC is a widely accepted measure to quantify trends in ASRs over specific time intervals and was calculated based on the regression model fitted to the natural logarithm of the rates. The 95% confidence intervals (CIs) were obtained from the same regression model. A negative upper limit for both EAPC and its CI indicates a declining trend; a positive lower limit indicates an increasing trend, and inclusion of zero signifies no significant trend. SDI is a composite measure of gross domestic product per capita, mean years of schooling, and fertility rate[ 12 ], reflecting social development and serving as a key indicator of disease burden and health progress. GBD 2021 classifies 204 countries and territories into five SDI categories: Low, Low-middle, Middle, High-middle, and High[ 13 ]. We also performed correlation analyses between SDI and ASIR, ASPR, ASMR, and ASDR to elucidate the relationship between thalassemia burden and socioeconomic development. 2.3 Joinpoint regression analysis The joinpoint regression model consists of linear statistical models designed to evaluate temporal trends in disease burdens attributable to thalassemia. The model accurately captured change points in the data and calculated APC, average annual percentage change (AAPC), and their 95% CIs. APC and AAPC values quantify temporal trends in disease burden indicators. A positive APC or AAPC, with a 95% CI that excludes zero, indicates an increasing ASR. Conversely, a negative APC or AAPC, with a 95% CI that remains below zero, denotes a declining ASR. We conducted this analysis utilizing the “Joinpoint” software (version 4.9.1.0) from the Surveillance Research Program of the US National Cancer Institute. 2.4 Autoregressive integrated moving average model projection We applied the autoregressive integrated moving average (ARIMA) model to project trends in four age-standardized indicators of thalassemia over the next nine years. By combining three principal elements—autoregression (AR), differencing (I), and moving average (MA)—the model efficiently identifies patterns and seasonal variations within time series data. The parameters, labeled p, d, and q, correspond to the autoregressive order, the degree of differencing, and the moving average order, respectively[ 14 ]. We assessed stationarity using the Augmented Dickey-Fuller (ADF) test, while the autocorrelation function (ACF) and partial autocorrelation function (PACF) were used to determine the optimal values of p and q. We selected the optimal ARIMA models using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) to project the thalassemia burden from 2021 to 2030, thereby minimizing potential bias introduced by subjective model selection. All statistical analyses and visualizations were performed using R software (version 4.4.1). A p-value of < 0.05 was considered statistically significant for trend analyses. 3 Results 3.1 Overview of thalassemia disease burden Utilizing comprehensive global data on thalassemia and thalassemia trait, this study systematically analyzed the spatial distribution patterns of total number of incident cases and ASIR, revealing significant regional variations in the disease burden. At the global level, the ASIR of thalassemia exhibited substantial variation across different regions (Fig. 1 A). In 2021, the ASIRs of thalassemia in Cambodia, Maldives, and Laos ranked among the top three globally (Fig. 1 B). China ranked sixth globally, with an ASIR of 7.6 (95% UI: 5.5–10.4) per 100,000 population in 2021. In terms of incident cases, China had the highest number worldwide in 2021, with 40,143.5 cases (95% UI: 29,325.4–54,927.5), followed by Bangladesh and Indonesia (Fig. 1 C, D). The ASIR of thalassemia trait also demonstrated marked geographic clustering, with the highest rate observed in the Maldives, followed by Thailand and Cambodia (Fig. 1 E). In 2021, the ASIR of thalassemia trait in China reached 200.8 (95% UI: 171.7-235.1) per 100,000 population, ranking fifth globally (Fig. 1 F). Regarding the number of thalassemia trait cases, China bore the greatest disease burden, with an estimated 1,064,507 (95% UI: 909,864.4-1,246,219.6) in 2021, significantly surpassing the numbers in other countries (Fig. 1 G, H). From 1990 to 2021, various epidemiological indicators for thalassemia and thalassemia trait in China exhibited distinct trends (Table 1 ). In 2021, the number of incident cases of thalassemia reached 40,143.5 (95% UI: 29,325.4–54,927.5), representing a 55.1% decline compared to 1990, and its ASIR demonstrated an overall downward trend over the past 32 years, with an EAPC of -0.60 (95% CI: -0.71 to -0.48). Similarly, the number of incident cases of thalassemia trait in 2021 decreased by 54.1% relative to 1990, and its ASIR also exhibited a downward trend, with an EAPC of -0.43 (95% CI: -0.52 to -0.34). In contrast, the ASPR for thalassemia showed no significant change from 1990 to 2021, with an EAPC of -0.02 (95% CI: -0.13 to 0.09). By comparison, the ASPR for thalassemia trait declined slightly during the same period, with an EAPC of -0.11 (95% CI: -0.20 to -0.02). The number of deaths due to thalassemia in 2021 decreased by 74.3% compared to 1990, and both its ASMR and ASDR declined from 1990 to 2021, with EAPCs of -4.90 (95% CI: -5.06 to -4.73) and − 5.10 (95% CI: -5.28 to -4.91), respectively. Similarly, the ASDR of thalassemia trait also exhibited a downward trend over the past 32 years, with an EAPC of -2.77 (95% CI: -2.86 to -2.67). Table 1 The numbers and ASRs of thalassemia and thalassemia trait in 1990 and 2021, and changing trends from 1990 to 2021 in China. Clinical group Measure sex Number in 1990 (n,95%UI) ASR in 1990 (n,95%UI) Number in 2021 (n,95%UI) ASR in 2021 (n,95%UI) EAPC _95%CI(n,95%UI) Thalassemia in China Incidence female 36736.5 (27151.9-49422.3) 7.2 (5.3–9.6) 16395.6 (11959.9-22479.6) 6.7 (4.9–9.2) -0.62 (-0.74 to -0.50) male 52605.2 (38613.5-71335.5) 8.9 (6.5–12) 23747.9 (17114.2-32608.3) 8.3 (6-11.4) -0.58 (-0.69 to -0.47) both 89341.7 (66031.2-120462.5) 8.1 (6-10.9) 40143.5 (29325.4-54927.5) 7.6 (5.5–10.4) -0.60 (-0.71 to -0.48) Prevalence female 293718.9 (233148.8-367836) 51 (40.5–64.3) 219789.4 (175608.8-272781.3) 48.7 (38.7–61.4) -0.04 (-0.15 to 0.06) male 403059.3 (314069.9-506821.3) 64.1 (49.9–80.4) 305741.8 (238859.7-388866.8) 61.3 (47.6–78.4) -0.02 (-0.13 to 0.10) both 696778.2 (549345.6-879546.9) 57.9 (45.4–73) 525531.2 (416346.2-665224.4) 55.4 (43.6–70.8) -0.02 (-0.13 to 0.09) Deaths female 3219.6 (1884.8-4793.6) 0.6 (0.3–0.9) 864.2 (547.2-1213.7) 0.1 (0.1–0.2) -4.99 (-5.16 to -4.82) male 4027.2 (3145.6–4856) 0.7 (0.5–0.8) 1001.3 (761.2-1253.4) 0.2 (0.1–0.2) -4.82 (-4.98 to -4.66) both 7246.8 (5536.3-9057.7) 0.6 (0.5–0.8) 1865.5 (1447.2-2319.3) 0.1 (0.1–0.2) -4.90 (-5.06 to -4.73) DALYs female 248682.7 (143772.1-382715.7) 45.8 (26.4–71) 52193.1 (34332.6-72174) 10.2 (6.6–13.8) -5.12 (-5.31 to -4.93) male 326652.2 (252527.7-392485.5) 53.9 (41.6–65) 64825.6 (50692.6-79299.5) 11.9 (9.4–14.7) -5.08 (-5.26 to -4.90) both 575335 (438078.9-728849.2) 50.1 (38.1–64) 117018.7 (93603.3-143747.8) 11.1 (8.9–13.8) -5.10 (-5.28 to -4.91) Thalassemia trait in China Incidence female 1008553.2 (867257.9-1175464.1) 196.4 (168.9-228.9) 458803.8 (392230.4-540744.2) 187.4 (160.2-220.9) -0.46 (-0.55 to -0.37) male 1308278.2 (1130052.4-1533352.9) 221 (190.9–259) 605703.3 (516775.2-709445.8) 212.4 (181.2-248.8) -0.41 (-0.50 to -0.32) both 2316831.5 (1998289.6-2697418.8) 209.6 (180.7–244) 1064507 (909864.4-1246219.6) 200.8 (171.7-235.1) -0.43 (-0.52 to -0.34) Prevalence female 51841337 (44509852.1-60478865) 9080.3 (7795.7-10594.1) 60918543.1 (51888196.8-71944538.1) 8903.4 (7590.5-10508.1) -0.11 (-0.20 to -0.03) male 62418771.1 (53822680.3-73352389.5) 10252 (8837–12049) 72681758.8 (61801638.9-85449870.8) 10089 (8585.1-11847.9) -0.10 (-0.19 to -0.01) Clinical group Measure sex Number in 1990 (n,95%UI) ASR in 1990 (n,95%UI) Number in 2021 (n,95%UI) ASR in 2021 (n,95%UI) EAPC_95%CI(n,95%UI) (Continued from previous page) Thalassemia trait in China Prevalence both 114260108.1 (98380518.9-133408040.9) 9683 (8336-11308.5) 133600301.9(113930347.4-156959555.3) 9517.2 (8123.2-11160.2) -0.11 (-0.20 to -0.02) Deaths female N/A N/A N/A N/A N/A male N/A N/A N/A N/A N/A both N/A N/A N/A N/A N/A DALYs female 417986.2 (270281.5-620762.4) 72.5 (47.2-107.3) 296729.8 (189783.7-447024.1) 41.1 (26.1–62.1) -2.00 (-2.10 to -1.90) male 264473.1 (171152.1-392439.4) 47.8 (31.1–70) 92046.2 (57796.7-146981) 14.1 (8.8–22.4) -4.26 (-4.39 to -4.13) both 682459.3 (440488.2-1013967.2) 59.7 (38.6–88.4) 388775.9 (249708.4-595782.8) 27.1 (17.4–41.8) -2.77 (-2.86 to -2.67) Abbreviations: ASR, Age-Standardized Rate; DALYs, Disability-adjusted Life Years; EAPC, Estimated Annual Percentage Change; 95 % CI, 95 % Confidence Interval; 95% UI, 95% Uncertainty Interval. 3.2 Disease burden of thalassemia in China by age and sex Following the assessment of the overall burden of thalassemia, we further analyzed the distribution across age groups and sexes in China. In 2021, the number of incident cases of thalassemia in males totaled 23,747.90 (95% UI: 17,114.15-32,608.25), surpassing females, who had 16,395.56 cases (95% UI: 11,959.92-22,479.56) (Table S1 and Fig. 2 A). In 2021, incidence rates of thalassemia were also higher in males than in females, at 57.04 (95% UI: 41.11–78.33) versus 45.50(95% UI: 33.19–62.38) per 100,000 population. Regarding number and rate of prevalence, individuals of both sexes in the < 5 age group peaked in 2021, with 164,116.86 cases (95% UI: 124,245.72–219,293.22) and a rate of 211.30 (95% UI: 159.97–282.35) per 100,000 population (Table S1 and Fig. 2 B). Among individuals under 40 years of age in China, the prevalence rate of thalassemia was consistently higher in males than in females in 2021. This trend reversed in the 40–44 age group and older, where females exhibited a higher prevalence of thalassemia compared to males of the same age. In 2021, the highest mortality rate of thalassemia among both sexes occurred among children aged < 5 age group, at 0.37 (95% UI: 0.25–0.50) per 100,000 population (Table S1 and Fig. 2 C). Notably, two peaks of mortality rate were observed among both sexes: one in the < 5 age group and another in the 50–54 age group. Among individuals aged 50–74 years, females in 2021 consistently exhibited higher mortality rates of thalassemia than males of the same age, whereas in all other age groups, mortality rates in males were greater than or equal to those of females. In 2021, DALYs and DALY rates of thalassemia in China displayed trends similar to the mortality rate (Table S1 and Fig. 2 D). In 2021, the overall DALY rates of thalassemia among both sexes declined with increasing age, except for a transient rise in the 20–24 and 40–54 age groups. Among individuals under 45 years of age, males in 2021 had consistently higher DALY rates due to thalassemia than females of the same age, while the reverse pattern was observed among those aged 45 years and above. 3.3 China and global trend analysis of thalassemia To further clarify the relative position of China in the global thalassemia burden, we compared the temporal trends of ASIR, ASPR, ASMR and ASDR in China with global trends from 1990 to 2021 (Table S2 and Fig. 3 ). In 2021, the number of incident cases of thalassemia in China accounted for 33.5% of the global total (Table S2 and Fig. 3 A). Notably, the ASIR of thalassemia in China in 2021 was 7.57 (95% UI: 5.53–10.36) per 100,000 population, far surpassing the global ASIR of 1.93 (95% UI: 1.51–2.49) per 100,000 population. The ASIR of thalassemia in China remained higher than the global level every year from 1990 to 2021. Although the ASIR of thalassemia in China demonstrated an overall declining trend from 1990 to 2021, it exhibited a consistent annual increase during the most recent five-year period (2017–2021). Prevalent thalassemia cases in China represented 40.1% of the global total in 2021 (Table S2 and Fig. 3 B). Similar to the ASIR, the ASPR of thalassemia in China exceeded the global rate every year over the past 32 years. In 2021, deaths of thalassemia in China accounted for 16.8% of global cases (Table S2 and Fig. 3 C). The ASMR of thalassemia in China declined steadily from 1990 to 2021 and remained equal to or below the global ASMR during the period from 2018 to 2021. The DALYs of thalassemia in China accounted for 14.3% of the global total in 2021 (Table S2 and Fig. 3 D). Similar to the ASMR, the ASDR of thalassemia in China showed a consistent decline over the past 32 years and remained lower than the global ASDR from 2018 to 2021. 3.4 Trajectories in disease burden of thalassemia in China based on joinpoint regression analysis To further clarify the temporal trends of thalassemia in China from 1990 to 2021, this study employed the joinpoint regression to quantify historical trajectories and identify joinpoints (Table S3, Table S4, and Fig. 4 ). Joinpoint regression analysis indicated that, between 1990 and 2021, the ASIR, ASMR, and ASDR of thalassemia in China declined overall, with AAPCs of -0.22% (95% CI: -0.34% to -0.10%, P < 0.001), -4.59% (95% CI: -4.77% to -4.40%, P < 0.001), and − 4.74% (95% CI: -4.91% to -4.56%, P < 0.001), respectively (Table S3 and Fig. 4 B–D). The ASPR of thalassemia in China showed no significant trend over the past 32 years, with an AAPC of -0.09% (95% CI: -0.18–0.01%, P = 0.072) (Table S3 and Fig. 4 A). Specifically, from 1990 to 2021, the ASIR of thalassemia in China exhibited a fluctuating trend (Table S4 and Fig. 4 A). During the period from 2019 to 2021, the ASIR of thalassemia in China demonstrated an increasing trend (APC = 3.43%, 95% CI: 2.08–4.80%, P < 0.001), representing the highest rate of increase over the past 32 years. In sex-specific analyses, a joinpoint in 2019 marked a shift from decline to increase in ASIR for both males and females. Similar to both sexes, the greatest ASIR increases occurred between 2019 and 2021 in both males (APC = 3.48%, 95% CI: 2.12–4.86%, P < 0.001) and females (APC = 3.29%, 95% CI: 2.02–4.58%, P < 0.001). Regarding the ASPR in China, the most pronounced declines from 1990 to 2021 occurred during 2019 to 2021, with APCs of -4.68% (95% CI: -5.91% to -3.42%, P < 0.001), -4.85% (95% CI: -5.94% to -3.74%, P < 0.001), and − 4.51% (95% CI: -5.95% to -3.06%, P < 0.001) for both sexes, males, and females, respectively (Table S4 and Fig. 4 B). From 1990 to 2021, the ASMR of thalassemia in China declined consistently across all periods (Table S4 and Fig. 4 C). The greatest declines in ASMR occurred between 2009 and 2013, with APCs of -6.70% (95% CI: -7.60% to -5.79%, P < 0.001) and − 6.90% (95% CI: -8.02% to -5.77%, P < 0.001) for both sexes and males, respectively. In females, the largest decline in ASMR was observed between 2003 and 2006 (APC = -6.50%, 95% CI: -7.52% to -5.47%, P < 0.001). Similarly, the ASDR of thalassemia in China declined throughout the period from 1990 to 2021 (Table S4 and Fig. 4 D). The largest reductions in ASDR occurred between 2009 and 2014, with an APC of -6.67% (95% CI: -7.21% to -6.12%, P < 0.001) for both sexes. In males and females, the greatest decline in ASDR was recorded during 2009–2013 (APC = -7.10%, 95% CI: -8.14% to -6.05%, P < 0.001) and 2003–2006 (APC = -6.68%, 95% CI: -8.13% to -5.21%, P < 0.001), respectively. 3.5 The association between the burden of thalassemia and SDI in China We assessed the association between the burden of thalassemia and SDI in China from 1990 to 2021 (Fig. 5 ). The results indicated a significant negative correlation between the ASIR of thalassemia and SDI (ρ= -0.842, P < 0.001) (Fig. 5 A). A negative correlation was observed between the ASPR of thalassemia in China and the SDI (ρ = − 0.234, P = 0.197), though this relationship did not achieve statistical significance (Fig. 5 B). For ASMR (ρ= -1.000, P < 0.001) (Fig. 5 C) and ASDR (ρ= -1.000, P < 0.001) (Fig. 5 D), the burden of thalassemia in China demonstrated an almost perfect negative linear relationship with SDI from 1990 to 2021. These findings indicate that as SDI increases in China, both the ASMR and ASDR of thalassemia show a substantial decline. 3.6 Changing trends in the prevalence of HF impairment with thalassemia in China HF due to iron overload is the most common and severe complication of thalassemia, significantly contributing to the overall disease burden[ 15 , 16 ]. Therefore, we further analyzed the number of prevalent cases and rates of HF impairment among individuals with thalassemia. In 2021, the absolute number of individuals with thalassemia combined with HF was highest in the < 5 age group, at 4,478.78 cases (95% UI: 2,877.33-6,753.44) (Table S5 and Figure S1 A), and the prevalence rate also peaked in this age group, reaching 5.77 per 100,000 population (95% UI: 3.70–8.70). Overall, among individuals under 25 years of age in China, males bore a greater burden of thalassemia combined with HF than females, as evidenced by higher number of cases. However, this trend reversed among individuals aged 25 years and older. Regarding prevalence rates in 2021, both males and females with thalassemia combined with HF exhibited their highest rates in the < 5 age group: 6.64 per 100,000 population for males (95% UI: 4.29–9.95) and 4.75 per 100,000 population for females (95% UI: 3.09–7.15). Additionally, we applied joinpoint regression analysis to assess the temporal trends in the ASPR of thalassemia combined with HF in China from 1990 to 2021 (Table S6, Table S7, and Figure S1 B). Over the past 32 years, the ASPR of thalassemia combined with HF in both sexes and females showed an increasing trend, with AAPCs of 0.10% (95% CI: 0.01–0.18%, P = 0.023) and 0.27% (95% CI: 0.19–0.34%, P < 0.001), respectively (Table S6 and Figure S1 B). In males, however, the ASPR of thalassemia combined with HF exhibited a declining trend, with an AAPC of -0.06% (95% CI: -0.10% to -0.02%, P < 0.001). Notably, the period between 2000 and 2005 exhibited the greatest increases in ASPR for thalassemia combined with HF, with APCs of 5.06% (95% CI: 4.59–5.53%, P < 0.001) for both sexes, 4.40% (95% CI: 4.16–4.64%, P < 0.001) for males, and 6.04% (95% CI: 5.83–6.25%, P < 0.001) for females, respectively (Table S7 and Figure S1 B). 3.7 Projections of thalassemia in China for the next 9 years We employed the ARIMA model to project trends in the ASIR, ASPR, ASMR, and ASDR of thalassemia in China through 2030. The ASIR of thalassemia in China is projected to increase from 7.57 per 100,000 population in 2021 to 8.94 per 100,000 population in 2030 (Table S8 and Figure S2A). Similarly, the ASPR is expected to rise from 55.44 per 100,000 population in 2021 to 58.31 per 100,000 population in 2030, indicating an overall increase in the burden of thalassemia (Table S8 and Figure S2B). Conversely, both the ASMR and ASDR are projected to show significant declines. The ASMR and ASDR of thalassemia in China are expected to decrease from 0.15 and 11.11 per 100,000 population in 2021 to 0.08 and 6.18 per 100,000 population in 2030, respectively, reflecting ongoing improvements in thalassemia management in China (Table S8 and Figure S2C, D). 4 Discussion This study utilized the GBD 2021 dataset, analyzing incidence, prevalence, mortality, and DALYs to assess temporal trends in the burden of thalassemia in China and globally from 1990 to 2021. In 2021, countries ranked among the top ten for both the number of incident cases and the ASIR of thalassemia were predominantly located in Southeast Asia, including Cambodia, Laos, Thailand, Myanmar, Vietnam, and Timor-Leste. These findings are consistent with previous studies[ 17 ]. Among the most populous nations in the world, China recorded the highest number of new thalassemia cases in 2021 and was the only East Asian country to appear in the global top ten for both incident cases and ASIR, underscoring its considerable thalassemia burden. Similarly, for thalassemia trait, China reported the highest number of incident cases globally, with its ASIR ranking fifth worldwide. Collectively, these results emphasize that both thalassemia and thalassemia trait impose substantial public health challenges in China, necessitating focused attention from communities, healthcare professionals, and policymakers. Primary prevention based on carrier screening, genetic counseling and prenatal diagnosis are essential to reduce the risk of thalassemia‑affected births[ 18 ]. Several studies have demonstrated that large-scale population screening, combined with molecular techniques in South and Southwest China, has significantly reduced rates of birth defect among high-risk couples[ 9 , 19 – 21 ]. However, the national incidence of thalassemia continues to fluctuate substantially. Specifically, between 2003 and 2011, China experienced the greatest decline in the ASIR of thalassemia. Yet, from 2019 to 2021, China observed the largest increase in the ASIR of thalassemia. We hypothesize that the observed fluctuations in the ASIR of thalassemia in China are closely linked to revisions in genetic disease screening policies at both national and subnational levels. At the national level, the Healthy China Initiative (2019–2030) incorporated genetic disease screening into 15 major programs and called for a systematic enhancement of birth defect prevention and control capacity[ 22 ]. The subsequent Birth Defect Prevention and Control Capacity Improvement Plan (2023–2027) set an ambitious target of achieving a prenatal screening rate of ≥ 90% by 2027, with thalassemia identified as a key target for intervention, further driving the expansion of genetic screening and case registration across regions[ 23 ]. At the provincial level, policies magnified this screening‑related ascertainment effect. In 2019, Guangxi implemented the Three-Year Action Plan for the Prevention and Control of Thalassemia in Guangxi (2019–2021), providing free carrier screening and a “zero affected birth” intervention program for severe thalassemia to couples of reproductive age[ 24 ]. The program reached more than one million high-risk individuals over three years, thereby integrating numerous previously undiagnosed cases into the surveillance system and likely contributing substantially to the observed increase in the ASIR of thalassemia during this period. Moreover, the ASMR and ASDR of thalassemia in China consistently declined across all observed periods. This decline likely reflects the implementation of multilevel, optimized thalassemia management interventions. With the expansion of universal medical insurance coverage, increased drug reimbursement, adoption of emerging therapies such as gene editing, and the support of social organization, thalassemia management in China is transitioning from traditional transfusion and iron chelation to more comprehensive continuum-of-care models[ 25 – 27 ]. Through comparing the associations between the SDI and the thalassemia burden in China from 1990 to 2021, we found that lower levels of development were generally associated with a heavier burden across multiple indicators. This trend can primarily be attributed to inadequate early‑stage healthcare resources, such as the absence of screening programs, outdated diagnostic technologies, and poor treatment accessibility. From 1990 to 2021 in China, the increasing SDI in China paralleled a shift in molecular diagnostics for thalassemia, from liquid DNA–DNA hybridization to next-generation sequencing (NGS)[ 28 ]. Regarding treatment, in addition to curative advances in hematopoietic stem cell transplantation, novel iron chelators, gene therapy agents, and CRISPR–Cas9 gene editing techniques have the potential to improve management of patients with thalassemia and may reduce complications[ 29 – 32 ]. With the support of the 2015 Precision Poverty Alleviation policy and the Healthy China Initiative 2030, thalassemia prevention and control programs in ten high-prevalence provinces, autonomous regions, and municipalities, such as Guangxi, have made substantial progress[ 9 , 33 ]. However, current thalassemia prevention and control programs remain concentrated in only a few southern provinces, and a comprehensive nationwide system has yet to be established. Future efforts should prioritize development of multifaceted strategies encompassing screening, prevention, treatment, public education, healthcare provider training, and the establishment of specialized centers and networks to reduce the disease burden of thalassemia across China. In terms of sex distribution, males generally bear a greater thalassemia burden. Disease burden data from China indicate that the ASDR for males was higher than that for females, both in 1990 and 2021. Among patients with severe thalassemia, cardiac disease remains the leading cause of death, accounting for 71% of fatalities, although survival rates have improved significantly with regular blood transfusions and iron chelation therapy[ 34 ]. Several studies have demonstrated that female thalassemia patients tend to have higher survival rates and a lower incidence of cardiac complications compared to male patients[ 35 – 37 ]. These sex‑specific patterns are consistent with our GBD 2021 findings. In 2021, the ASPR of thalassemia combined with HF was higher in males than in females, at 1.48 and 1.31 per 100,000 population, respectively. In β-thalassemia, pathways involved in oxidative stress defense, lipid metabolism, and erythropoietin activity show sex-related differences, although current evidence remains limited[ 38 – 40 ]. Furthermore, regarding age distribution, thalassemia, a common monogenic disorder, predominantly affects children under the age of five. However, our study also identified a secondary peak in the ASMR and ASDR of thalassemia in individuals aged 50–54 years in 2021. In China, the accelerating trend of population aging is likely to exacerbate this phenomenon. This shift in disease burden could have significant implications for healthcare resource allocation and social security systems, necessitating careful planning and policy adjustments. This study provides a comprehensive comparison of thalassemia characteristics in China and globally, revealing notable differences between China and other regions. To our knowledge, this GBD 2021–based analysis of thalassemia burden in China represents the most comprehensive analysis to date, emphasizes the necessity of targeted interventions, and highlights key populations that should be prioritized. However, several limitations should be acknowledged. First, the GBD data are derived from cleaned and compiled reported sources, which are then adjusted through modeling techniques, rather than being directly derived from real‑world data collected in each country. This modeling approach may introduce estimation bias and uncertainty. Second, while there are significant regional disparities in prevalence of thalassemia across provinces in China, the GBD 2021 database lacks province-level (subnational) stratification, limiting the ability to conduct detailed subnational analyses. Finally, the lack of detailed differentiation between α- and β-thalassemia subtypes in the GBD 2021 data may have hindered the assessment of subtype-specific epidemiological patterns and disease burden. 5 Conclusions This study utilized GBD 2021 estimates to provide a comprehensive assessment of the thalassemia burden in China from 1990 to 2021. Although the ASMR and ASDR of thalassemia in China have generally decreased, the overall burden remains a significant public health challenge. Across sexes, the thalassemia burden is greater in males than in females. While advances in early screening and treatment have alleviated this burden to some extent, challenges from an aging demographic and large population base remain. Future initiatives should focus on equitable resource allocation, particularly in underserved and remote areas, by improving early screening, expanding health education, and optimizing treatment strategies to further reduce the thalassemia burden. Abbreviations GBD Global Burden of Disease ASRs Age‑standardized rates DALYs Disability‑adjusted life years ARIMA Autoregressive integrated moving average ASIR Age‑standardized incidence rate ASMR Age‑standardized mortality rate ASPR Age‑standardized prevalence rate ASDR Age‑standardized DALYs rate EAPCs Estimated annual percentage changes CODEm Cause of Death Ensemble model ST‑GPR Spatiotemporal Gaussian process regression UIs Uncertainty intervals CIs Confidence intervals SDI Socio‑demographic index APC Annual percentage change AAPC Average annual percentage change ADF Augmented Dickey–Fuller test ACF Autocorrelation function PACF Partial autocorrelation function AIC Akaike Information Criterion BIC Bayesian Information Criterion NGS Next‑generation sequencing Declarations Availability of data and materials The data used in this study are freely available from the Global Health Data Exchange (GHDx) website (http://ghdx.healthdata.org/gbd-results-tool). The datasets analyzed during the current study are available from the corresponding author upon reasonable request. Authors' contributions X.P. and X.B. analyzed the data, performed data visualization, and drafted the initial manuscript. S.G., W.W., L.T. and K.H. contributed to data collection and quality control. Y.S., F.Y., L.Z. and R.L. participated in the data preparation and verified the data. H.P., Z.G., W.L., J.Z., X.Y. reviewed and revised the manuscript. J.S. and Z.K. conceptualized the study, designed the manuscript framework, and supervised the project. All authors contributed to the work and approved the final version for submission. Acknowledgments Thanks to the Institute for Health Metrics and Evaluation (IHME) and the Global Burden of Disease study collaborations. Funding This work was supported by grants from the National Key R&D Program of China (2024YFC2510500), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, CIFMS (2024-I2M-ZH-021, 2022-I2M-2-003, 2021-I2M-1-073, 2023-I2M-2-007), the National Natural Science Foundation of China (82270145, 82300162, 82100145), and Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0037). Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018;391(10116):155–67. Lal A, Vichinsky E. The Clinical Phenotypes of Alpha Thalassemia. Hematol Oncol Clin North Am. 2023;37(2):327–39. Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet. 2022;399(10343):2310–24. Musallam KM, Cappellini MD, Coates TD, Kuo KHM, Al-Samkari H, Sheth S, et al. Αlpha-thalassemia: A practical overview. Blood Rev. 2024;64:101165. Casale M, Meloni A, Filosa A, Cuccia L, Caruso V, Palazzi G, et al. Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study. Circ Cardiovasc Imaging. 2015;8(8):e003230. Rivella S. β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica. 2015;100(4):418–30. Musallam KM, Lombard L, Kistler KD, Arregui M, Gilroy KS, Chamberlain C, et al. Epidemiology of clinically significant forms of alpha- and beta-thalassemia: A global map of evidence and gaps. Am J Hematol. 2023;98(9):1436–51. Flint J, Hill AV, Bowden DK, Oppenheimer SJ, Sill PR, Serjeantson SW, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature. 1986;321(6072):744–50. Wang WD, Hu F, Zhou DH, Gale RP, Lai YR, Yao HX, et al. Thalassaemia in China. Blood Rev. 2023;60:101074. Lai K, Huang G, Su L, He Y. The prevalence of thalassemia in mainland China: evidence from epidemiological surveys. Sci Rep. 2017;7(1):920. Global incidence. prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133–61. Liu P, Wang Y, Tian Z, Dong X, Li Z, Chen Y. Global, regional, and national burden of pancreatitis in children and adolescents. United Eur Gastroenterol J. 2025;13(3):376–91. Bai Z, Han J, An J, Wang H, Du X, Yang Z, et al. The global, regional, and national patterns of change in the burden of congenital birth defects, 1990–2021: an analysis of the global burden of disease study 2021 and forecast to 2040. EClinicalMedicine. 2024;77:102873. Wu Y, Xia F, Chen M, Zhang S, Yang Z, Gong Z, et al. Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024. BMC Public Health. 2023;23(1):122. Meloni A, Pistoia L, Positano V, De Luca A, Martini N, Spasiano A, et al. Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major. Eur Radiol. 2023;33(2):1266–76. Pinto VM, Forni GL. Management of Iron Overload in Beta-Thalassemia Patients: Clinical Practice Update Based on Case Series. Int J Mol Sci 2020, 21(22). Tuo Y, Li Y, Li Y, Ma J, Yang X, Wu S et al. Global, regional, and national burden of thalassemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. EClinicalMedicine 2024, 72:102619. Ip HW, So CC. Diagnosis and prevention of thalassemia. Crit Rev Clin Lab Sci. 2013;50(6):125–41. Liao C, Zhou JY, Xie XM, Li DZ. Screening for Hb Constant Spring in the Guangdong Province, South China, using the Sebia capillary electrophoresis system. Hemoglobin. 2011;35(1):87–90. Lin M, Wang Q, Zheng L, Huang Y, Lin F, Lin CP, et al. Prevalence and molecular characterization of abnormal hemoglobin in eastern Guangdong of southern China. Clin Genet. 2012;81(2):165–71. He J, Song W, Yang J, Lu S, Yuan Y, Guo J, et al. Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China. Genet Med. 2017;19(9):1022–31. Healthy China Initiative. (2019–2030) [ http://www.gov.cn/xinwen/2019-07/15/content_5409694.htm] Birth Defect Prevention and Control Capacity Improvement Plan. (2023–2027) [ https://www.gov.cn/zhengce/zhengceku/202308/content_6900320.htm] Three-Year Action Plan for the Prevention and Control of Thalassemia in Guangxi. (2019–2021) [ http://www.gxzf.gov.cn/zwgk/zfxxgkzl_84988/zcwj_885018/xzgfxwj/t13714862.shtml] Beijing Angel Mother Charity Foundation CIoPW, Beijing Normal University: The Blue Book of Thalassemia in China: Investigation Report on the Prevention and Treatment of Thalassemia in China. (2020). Beijing: China Social Publishing House; 2021. Fu B, Liao J, Chen S, Li W, Wang Q, Hu J, et al. CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric β(0)/β(0) transfusion-dependent β-thalassemia. Nat Med. 2022;28(8):1573–80. Liu R, Xu H, Liang J, Xie W, Yang G, Shi L, et al. Preliminary Result of the Safety and Efficacy of Autologous HBG1/2 Promoter-Modified CD34 + Hematopoietic Stem and Progenitor Cells (RM-001) in Transfusion-Dependent Βeta-Thalassemia. Blood. 2022;140:4915–6. Zhang J, Yan J, Zeng F. Recent Progress on Genetic Diagnosis and Therapy for β-Thalassemia in China and Around the World. Hum Gene Ther. 2018;29(2):197–203. Algeri M, Lodi M, Locatelli F. Hematopoietic Stem Cell Transplantation in Thalassemia. Hematol Oncol Clin North Am. 2023;37(2):413–32. Asghar AA, Khabir Y, Hashmi MR. Zynteglo: Betibeglogene autotemcel - An innovative therapy for β- thalassemia patients. Ann Med Surg (Lond). 2022;82:104624. Cetin B, Erendor F, Eksi YE, Sanlioglu AD, Sanlioglu S. Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects. Expert Rev Mol Med. 2025;27:e16. Takpradit C, Viprakasit V, Narkbunnam N, Vathana N, Phuakpet K, Pongtanakul B, et al. Using of deferasirox and deferoxamine in refractory iron overload thalassemia. Pediatr Int. 2021;63(4):404–9. The 3 year action plan for prevention. and control of thalassemia in Guangxi [ http://www.gxzf.gov.cn/zfgb/2019nzfgb/d9q_35420/zzqrmzfbgtwj_35422/t1514507.shtml] Marsella M, Pepe A, Borgna-Pignatti C. Better survival and less cardiac morbidity in female patients with thalassemia major: a review of the literature. Ann N Y Acad Sci. 2010;1202:129–33. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89(10):1187–93. Chouliaras G, Yiannoutsos CT, Berdoukas V, Ladis V. Cardiac related death in thalassaemia major: time trend and risk factors in a large Greek Unit. Eur J Haematol. 2009;82(5):381–7. Telfer PT, Warburton F, Christou S, Hadjigavriel M, Sitarou M, Kolnagou A, et al. Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone. Haematologica. 2009;94(12):1777–8. Kander MC, Cui Y, Liu Z. Gender difference in oxidative stress: a new look at the mechanisms for cardiovascular diseases. J Cell Mol Med. 2017;21(5):1024–32. Link JC, Reue K. Genetic Basis for Sex Differences in Obesity and Lipid Metabolism. Annu Rev Nutr. 2017;37:225–45. Soliz J, Khemiri H, Caravagna C, Seaborn T. Erythropoietin and the sex-dimorphic chemoreflex pathway. Adv Exp Med Biol. 2012;758:55–62. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial.xls 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. 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Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYDACCcYGAwYGGx4DUrWkkaQFTB5mIF6L/OzmhmLeHedlzNkPP934g8FOnoH97AG8WgzuHGww5j1zm8eyJ83sNg9DsmEDT14Cfi0SiUAtbbd5DG4wmN1mYGBOYJAg4C/5GWAt54Ba2L/d/MFQT1gLww2wlgNALTxmN3gYDhPWYgDUYji3LZnH4ExOGdB5xw3beHIIOSz9mcHbNjt7g+PHt938UVEtz89+hmCAsyGpADLZCKkHAuYHRCgaBaNgFIyCkQwAA78/CAa6ScMAAAAASUVORK5CYII=","orcid":"","institution":"National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"Jun","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2025-08-12 01:23:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7350201/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7350201/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91075727,"identity":"22a3f024-e277-4994-aad2-78b207704649","added_by":"auto","created_at":"2025-09-11 11:08:30","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":965118,"visible":true,"origin":"","legend":"\u003cp\u003eThe global disease burden of thalassemia and thalassemia trait in 2021. \u003cstrong\u003eA.\u003c/strong\u003e The ASIR of thalassemia in 204 countries and territories. \u003cstrong\u003eB.\u003c/strong\u003e The number of incident cases of thalassemia in the top 10 countries and territories. \u003cstrong\u003eC.\u003c/strong\u003e The ASIR of thalassemia trait in 204 countries and territories. \u003cstrong\u003eD.\u003c/strong\u003e The number of incident cases of thalassemia trait in the top 10 countries and territories. \u003cstrong\u003eAbbreviations:\u003c/strong\u003eASIR, Age-standardized Incidence Rate.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/9c0cbe680abba5ff8cf7a485.jpeg"},{"id":91073734,"identity":"3352417b-34b1-43c6-8975-8ea95cbf4760","added_by":"auto","created_at":"2025-09-11 11:00:30","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":622572,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence, prevalence, mortality, and DALYs in China for thalassemia by sex and age group in 2021. \u003cstrong\u003eA.\u003c/strong\u003e The incidence of thalassemia. \u003cstrong\u003eB.\u003c/strong\u003e The prevalence of thalassemia. \u003cstrong\u003eC.\u003c/strong\u003e The mortality of thalassemia. \u003cstrong\u003eD.\u003c/strong\u003e The DALYs of thalassemia. \u003cstrong\u003eAbbreviations:\u003c/strong\u003eDALYs, Disability-adjusted Life Years.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/2ad25a5e70f5d7724cfa0fa1.jpeg"},{"id":91073738,"identity":"a55583f7-c4a3-4997-b523-851ff2c89556","added_by":"auto","created_at":"2025-09-11 11:00:30","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1020774,"visible":true,"origin":"","legend":"\u003cp\u003eThe incidence, prevalence, mortality, and DALYs of thalassemia in China and globally from 1990 to 2021. \u003cstrong\u003eA.\u003c/strong\u003e Trends in the incidence in China and worldwide. \u003cstrong\u003eB.\u003c/strong\u003e Trends in the prevalence in China and worldwide. \u003cstrong\u003eC.\u003c/strong\u003e Trends in the mortality in China and worldwide. \u003cstrong\u003eD.\u003c/strong\u003eTrends in the DALYs in China and worldwide. \u003cstrong\u003eAbbreviations:\u003c/strong\u003e DALYs, Disability-adjusted Life Years.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/2b4eacb2ec6f0cf8f0071e98.jpeg"},{"id":91073745,"identity":"db89152d-1a06-43b8-9758-6ffa6bf6b262","added_by":"auto","created_at":"2025-09-11 11:00:30","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":881087,"visible":true,"origin":"","legend":"\u003cp\u003eJoinpoint regression analysis of the sex-specific ASRs of thalassemia in China from 1990 to 2021. \u003cstrong\u003eA.\u003c/strong\u003e ASIR of thalassemia. \u003cstrong\u003eB.\u003c/strong\u003e ASPR of thalassemia. \u003cstrong\u003eC.\u003c/strong\u003e ASMR of thalassemia. \u003cstrong\u003eD.\u003c/strong\u003eASDR of thalassemia. \u003cstrong\u003eAbbreviations:\u003c/strong\u003e ASR, Age-standardized Rate; ASIR, Age-standardized Incidence Rate; ASPR, Age-standardized Prevalence Rate; ASMR, Age-standardized Mortality Rate; ASDR, Age-standardized DALYs Rate; DALYs, Disability-adjusted Life Years; APC, Average Percentage Change.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/7881b72aa2323f6698d262bd.jpeg"},{"id":91073750,"identity":"dc6663a5-9b5a-4c62-8e0f-6210327fc977","added_by":"auto","created_at":"2025-09-11 11:00:30","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":568339,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between ASRs and SDI in thalassemia in China from 1990 to 2021. \u003cstrong\u003eA.\u003c/strong\u003e The association between ASIR and SDI. \u003cstrong\u003eB.\u003c/strong\u003e The association between ASPR and SDI. \u003cstrong\u003eC.\u003c/strong\u003e The association between ASMR and SDI. \u003cstrong\u003eD.\u003c/strong\u003e The association between ASDR and SDI. \u003cstrong\u003eAbbreviations:\u003c/strong\u003e ASR, Age-standardized Rate; ASIR, Age-standardized Incidence Rate; ASPR, Age-standardized Prevalence Rate; ASMR, Age-standardized Mortality Rate; ASDR, Age-standardized DALYs Rate; DALYs, Disability-adjusted Life Years.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/0d74984344f4af057d52c41f.jpeg"},{"id":91543108,"identity":"d6e97180-10af-4201-ad3d-efd5cc7290ea","added_by":"auto","created_at":"2025-09-17 14:17:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5249650,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/536d7e85-74f8-4950-8362-b02542be7801.pdf"},{"id":91073739,"identity":"30282825-7285-4dec-a13e-a38ef8874fec","added_by":"auto","created_at":"2025-09-11 11:00:30","extension":"xls","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2143232,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.xls","url":"https://assets-eu.researchsquare.com/files/rs-7350201/v1/106fba4f1cb39bfe966c2620.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"Temporal trends in the disease burden of thalassemia in China from 1990 to 2021 and forecast to 2030","fulltext":[{"header":"1 Background","content":"\u003cp\u003eThalassemia, a group of monogenic disorders caused by mutations in α- or β-globin genes, is classified into α-thalassemia and β-thalassemia based on the affected globin chain[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].An imbalance between α- and β-globin chain production leads to ineffective erythropoiesis and chronic hemolysis, which underlies the disease pathophysiology. In α-thalassemia major, reduced synthesis of α-globin chains results in an imbalance of the α- and β-globin, causing hypoproteinemia and cardiac insufficiency; most affected individuals succumb either in the late gestational period or shortly after birth[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In β-thalassemia major, defective β-globin synthesis results in severe anemia, requiring lifelong transfusion dependence and leading to complications such as iron overload\u0026ndash;induced cardiac and hepatic damage[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. As an incurable condition, thalassemia requires lifelong multidisciplinary management to address chronic iron overload, multisystem complications, and the increased risk of malignancy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGlobally, thalassemia displays pronounced geographical heterogeneity, with high-prevalence regions (\u0026gt;\u0026thinsp;5%) predominantly located in historically malaria-endemic areas of Asia, the Middle East, and the Mediterranean, while prevalence remains low (\u0026lt;\u0026thinsp;0.1%) in Europe and North America[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A primary driver underlying these distribution patterns is the overlap between historical malaria-endemic areas (particularly \u003cem\u003ePlasmodium falciparum\u003c/em\u003e) and thalassemia hotspots. Heterozygous carriers of thalassemia mutations experience a survival advantage in malaria-endemic regions due to red blood cell abnormalities that inhibit plasmodial parasitism, thereby promoting natural selection and the genetic dissemination of thalassemia mutations[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The distribution of thalassemia may also be influenced by multiple factors, including genetic evolution, environmental pressures, population migration, and healthcare availability. Consequently, due to these geographical, genetic, and demographic factors, including the large population in China, the country now bears the highest global burden of thalassemia, with approximately 30\u0026nbsp;million individuals harboring thalassemia-related mutations[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In China, the overall prevalence of α-thalassemia, β-thalassemia, and combined α\u0026thinsp;+\u0026thinsp;β-thalassemia are 7.88%, 2.21%, and 0.48%, respectively[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, analyzing long-term trends and epidemiological characteristics of thalassemia in China is crucial for developing effective prevention and control strategies.\u003c/p\u003e\u003cp\u003eDespite its significant public health impact, research on thalassemia in China remains limited. Leveraging standardized methodologies and epidemiological data, the Global Burden of Disease, Injuries, and Risk Factors Study 2021 (GBD 2021), which encompasses health statistics from 204 countries and territories, has expanded upon previous findings. Utilizing GBD 2021 data, this study systematically analyzes temporal trends in thalassemia in China from 1990 to 2021, focusing on key indicators such as incidence, prevalence, mortality, disability-adjusted life years (DALYs), the socio-demographic index (SDI), and average percentage change (APC). The objective of this study is to assess the most recent advancements in the epidemiology of thalassemia, address existing knowledge gaps, and guide the development of health policies and resource allocation strategies.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Overview\u003c/h2\u003e\u003cp\u003eThe GBD 2021 estimated the health loss due to 371 diseases and injuries using 100,983 data sources from 204 countries and territories. The original data were collected from disease-specific registries, health service contact data, vital registration systems, censuses, household surveys, and other sources[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The dataset utilized in this analysis is publicly accessible through the GHDx query tool at \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. The principal methods for estimating incidence, prevalence, mortality, and DALYs by age, sex, year, and location in GBD 2021 included the Cause of Death Ensemble model (CODEm), Spatiotemporal Gaussian process regression (ST-GPR), and the Bayesian meta-regression tool DisMod-MR.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Disease burden indicators\u003c/h2\u003e\u003cp\u003eWe extracted disease burden metrics with 95% uncertainty intervals (UIs), including absolute numbers and age-standardized rates (ASRs) per 100,000 population for incidence, prevalence, mortality, and disability-adjusted life years (DALYs), referred to as the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Furthermore, we calculated the estimated annual percentage change (EAPC) to evaluate temporal trends in the burden of thalassemia from 1990 to 2021. The EAPC is a widely accepted measure to quantify trends in ASRs over specific time intervals and was calculated based on the regression model fitted to the natural logarithm of the rates. The 95% confidence intervals (CIs) were obtained from the same regression model. A negative upper limit for both EAPC and its CI indicates a declining trend; a positive lower limit indicates an increasing trend, and inclusion of zero signifies no significant trend.\u003c/p\u003e\u003cp\u003eSDI is a composite measure of gross domestic product per capita, mean years of schooling, and fertility rate[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], reflecting social development and serving as a key indicator of disease burden and health progress. GBD 2021 classifies 204 countries and territories into five SDI categories: Low, Low-middle, Middle, High-middle, and High[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We also performed correlation analyses between SDI and ASIR, ASPR, ASMR, and ASDR to elucidate the relationship between thalassemia burden and socioeconomic development.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Joinpoint regression analysis\u003c/h2\u003e\u003cp\u003eThe joinpoint regression model consists of linear statistical models designed to evaluate temporal trends in disease burdens attributable to thalassemia. The model accurately captured change points in the data and calculated APC, average annual percentage change (AAPC), and their 95% CIs. APC and AAPC values quantify temporal trends in disease burden indicators. A positive APC or AAPC, with a 95% CI that excludes zero, indicates an increasing ASR. Conversely, a negative APC or AAPC, with a 95% CI that remains below zero, denotes a declining ASR. We conducted this analysis utilizing the \u0026ldquo;Joinpoint\u0026rdquo; software (version 4.9.1.0) from the Surveillance Research Program of the US National Cancer Institute.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Autoregressive integrated moving average model projection\u003c/h2\u003e\u003cp\u003eWe applied the autoregressive integrated moving average (ARIMA) model to project trends in four age-standardized indicators of thalassemia over the next nine years. By combining three principal elements\u0026mdash;autoregression (AR), differencing (I), and moving average (MA)\u0026mdash;the model efficiently identifies patterns and seasonal variations within time series data. The parameters, labeled p, d, and q, correspond to the autoregressive order, the degree of differencing, and the moving average order, respectively[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. We assessed stationarity using the Augmented Dickey-Fuller (ADF) test, while the autocorrelation function (ACF) and partial autocorrelation function (PACF) were used to determine the optimal values of p and q. We selected the optimal ARIMA models using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) to project the thalassemia burden from 2021 to 2030, thereby minimizing potential bias introduced by subjective model selection.\u003c/p\u003e\u003cp\u003eAll statistical analyses and visualizations were performed using R software (version 4.4.1). A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant for trend analyses.\u003c/p\u003e\u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Overview of thalassemia disease burden\u003c/h2\u003e\u003cp\u003eUtilizing comprehensive global data on thalassemia and thalassemia trait, this study systematically analyzed the spatial distribution patterns of total number of incident cases and ASIR, revealing significant regional variations in the disease burden. At the global level, the ASIR of thalassemia exhibited substantial variation across different regions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). In 2021, the ASIRs of thalassemia in Cambodia, Maldives, and Laos ranked among the top three globally (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). China ranked sixth globally, with an ASIR of 7.6 (95% UI: 5.5\u0026ndash;10.4) per 100,000 population in 2021. In terms of incident cases, China had the highest number worldwide in 2021, with 40,143.5 cases (95% UI: 29,325.4\u0026ndash;54,927.5), followed by Bangladesh and Indonesia (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, D). The ASIR of thalassemia trait also demonstrated marked geographic clustering, with the highest rate observed in the Maldives, followed by Thailand and Cambodia (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). In 2021, the ASIR of thalassemia trait in China reached 200.8 (95% UI: 171.7-235.1) per 100,000 population, ranking fifth globally (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF). Regarding the number of thalassemia trait cases, China bore the greatest disease burden, with an estimated 1,064,507 (95% UI: 909,864.4-1,246,219.6) in 2021, significantly surpassing the numbers in other countries (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG, H).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFrom 1990 to 2021, various epidemiological indicators for thalassemia and thalassemia trait in China exhibited distinct trends (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, the number of incident cases of thalassemia reached 40,143.5 (95% UI: 29,325.4\u0026ndash;54,927.5), representing a 55.1% decline compared to 1990, and its ASIR demonstrated an overall downward trend over the past 32 years, with an EAPC of -0.60 (95% CI: -0.71 to -0.48). Similarly, the number of incident cases of thalassemia trait in 2021 decreased by 54.1% relative to 1990, and its ASIR also exhibited a downward trend, with an EAPC of -0.43 (95% CI: -0.52 to -0.34). In contrast, the ASPR for thalassemia showed no significant change from 1990 to 2021, with an EAPC of -0.02 (95% CI: -0.13 to 0.09). By comparison, the ASPR for thalassemia trait declined slightly during the same period, with an EAPC of -0.11 (95% CI: -0.20 to -0.02). The number of deaths due to thalassemia in 2021 decreased by 74.3% compared to 1990, and both its ASMR and ASDR declined from 1990 to 2021, with EAPCs of -4.90 (95% CI: -5.06 to -4.73) and \u0026minus;\u0026thinsp;5.10 (95% CI: -5.28 to -4.91), respectively. Similarly, the ASDR of thalassemia trait also exhibited a downward trend over the past 32 years, with an EAPC of -2.77 (95% CI: -2.86 to -2.67).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe numbers and ASRs of thalassemia and thalassemia trait in 1990 and 2021, and changing trends from 1990 to 2021 in China.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMeasure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003esex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNumber in 1990\u003c/p\u003e\u003cp\u003e(n,95%UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eASR in 1990\u003c/p\u003e\u003cp\u003e(n,95%UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNumber in 2021\u003c/p\u003e\u003cp\u003e(n,95%UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eASR \u003c/p\u003e\u003cp\u003ein 2021\u003c/p\u003e\u003cp\u003e(n,95%UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEAPC\u003c/p\u003e\u003cp\u003e_95%CI(n,95%UI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"11\" rowspan=\"12\"\u003e\u003cp\u003eThalassemia in China\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eIncidence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36736.5 (27151.9-49422.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.2 (5.3\u0026ndash;9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16395.6 (11959.9-22479.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.7 (4.9\u0026ndash;9.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.62 (-0.74 to -0.50)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52605.2 (38613.5-71335.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.9 (6.5\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23747.9 (17114.2-32608.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.3 (6-11.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.58 (-0.69 to -0.47)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e89341.7 (66031.2-120462.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.1 (6-10.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40143.5 (29325.4-54927.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.6 (5.5\u0026ndash;10.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.60 (-0.71 to -0.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ePrevalence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e293718.9 (233148.8-367836)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e51 (40.5\u0026ndash;64.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e219789.4 (175608.8-272781.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e48.7 (38.7\u0026ndash;61.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.04 (-0.15 to 0.06)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e403059.3 (314069.9-506821.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e64.1 (49.9\u0026ndash;80.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e305741.8 (238859.7-388866.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e61.3 (47.6\u0026ndash;78.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.02 (-0.13 to 0.10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e696778.2 (549345.6-879546.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e57.9 (45.4\u0026ndash;73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e525531.2 (416346.2-665224.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e55.4 (43.6\u0026ndash;70.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.02 (-0.13 to 0.09)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eDeaths\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3219.6 (1884.8-4793.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6 (0.3\u0026ndash;0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e864.2 (547.2-1213.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.1 (0.1\u0026ndash;0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-4.99 (-5.16 to -4.82)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4027.2 (3145.6\u0026ndash;4856)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7 (0.5\u0026ndash;0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1001.3 (761.2-1253.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.2 (0.1\u0026ndash;0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-4.82 (-4.98 to -4.66)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7246.8 (5536.3-9057.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6 (0.5\u0026ndash;0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1865.5 (1447.2-2319.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.1 (0.1\u0026ndash;0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-4.90 (-5.06 to -4.73)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eDALYs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e248682.7 (143772.1-382715.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45.8 (26.4\u0026ndash;71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e52193.1 (34332.6-72174)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.2 (6.6\u0026ndash;13.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-5.12 (-5.31 to -4.93)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e326652.2 (252527.7-392485.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e53.9 (41.6\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e64825.6 (50692.6-79299.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.9 (9.4\u0026ndash;14.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-5.08 (-5.26 to -4.90)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e575335 (438078.9-728849.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50.1 (38.1\u0026ndash;64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e117018.7 (93603.3-143747.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.1 (8.9\u0026ndash;13.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-5.10 (-5.28 to -4.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003eThalassemia trait in China\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eIncidence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1008553.2 (867257.9-1175464.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e196.4 (168.9-228.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e458803.8 (392230.4-540744.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e187.4 (160.2-220.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.46 (-0.55 to -0.37)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1308278.2 (1130052.4-1533352.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e221 (190.9\u0026ndash;259)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e605703.3 (516775.2-709445.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e212.4 (181.2-248.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.41 (-0.50 to -0.32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2316831.5 (1998289.6-2697418.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e209.6 (180.7\u0026ndash;244)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1064507 (909864.4-1246219.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e200.8 (171.7-235.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.43 (-0.52 to -0.34)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePrevalence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51841337 (44509852.1-60478865)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9080.3 (7795.7-10594.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e60918543.1 (51888196.8-71944538.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8903.4 (7590.5-10508.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.11 (-0.20 to -0.03)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62418771.1 (53822680.3-73352389.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10252 (8837\u0026ndash;12049)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e72681758.8 (61801638.9-85449870.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10089 (8585.1-11847.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.10 (-0.19 to -0.01)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMeasure\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003esex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNumber in 1990\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n,95%UI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eASR in 1990\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n,95%UI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eNumber in 2021\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n,95%UI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eASR in 2021\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n,95%UI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eEAPC_95%CI(n,95%UI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003e(Continued from previous page)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eThalassemia trait in China\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePrevalence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e114260108.1 (98380518.9-133408040.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9683 (8336-11308.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e133600301.9(113930347.4-156959555.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9517.2 (8123.2-11160.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.11 (-0.20 to -0.02)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eDeaths\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eDALYs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e417986.2 (270281.5-620762.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e72.5 (47.2-107.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e296729.8 (189783.7-447024.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e41.1 (26.1\u0026ndash;62.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-2.00 (-2.10 to -1.90)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e264473.1 (171152.1-392439.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.8 (31.1\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e92046.2 (57796.7-146981)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14.1 (8.8\u0026ndash;22.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-4.26 (-4.39 to -4.13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eboth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e682459.3 (440488.2-1013967.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e59.7 (38.6\u0026ndash;88.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e388775.9 (249708.4-595782.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.1 (17.4\u0026ndash;41.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-2.77 (-2.86 to -2.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e ASR, Age-Standardized Rate; DALYs, Disability-adjusted Life Years; EAPC, Estimated Annual Percentage Change; 95 % CI, 95 % Confidence Interval; 95% UI, 95% Uncertainty Interval.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Disease burden of thalassemia in China by age and sex\u003c/h2\u003e\u003cp\u003eFollowing the assessment of the overall burden of thalassemia, we further analyzed the distribution across age groups and sexes in China. In 2021, the number of incident cases of thalassemia in males totaled 23,747.90 (95% UI: 17,114.15-32,608.25), surpassing females, who had 16,395.56 cases (95% UI: 11,959.92-22,479.56) (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). In 2021, incidence rates of thalassemia were also higher in males than in females, at 57.04 (95% UI: 41.11\u0026ndash;78.33) versus 45.50(95% UI: 33.19\u0026ndash;62.38) per 100,000 population. Regarding number and rate of prevalence, individuals of both sexes in the \u0026lt;\u0026thinsp;5 age group peaked in 2021, with 164,116.86 cases (95% UI: 124,245.72\u0026ndash;219,293.22) and a rate of 211.30 (95% UI: 159.97\u0026ndash;282.35) per 100,000 population (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Among individuals under 40 years of age in China, the prevalence rate of thalassemia was consistently higher in males than in females in 2021. This trend reversed in the 40\u0026ndash;44 age group and older, where females exhibited a higher prevalence of thalassemia compared to males of the same age. In 2021, the highest mortality rate of thalassemia among both sexes occurred among children aged\u0026thinsp;\u0026lt;\u0026thinsp;5 age group, at 0.37 (95% UI: 0.25\u0026ndash;0.50) per 100,000 population (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Notably, two peaks of mortality rate were observed among both sexes: one in the \u0026lt;\u0026thinsp;5 age group and another in the 50\u0026ndash;54 age group. Among individuals aged 50\u0026ndash;74 years, females in 2021 consistently exhibited higher mortality rates of thalassemia than males of the same age, whereas in all other age groups, mortality rates in males were greater than or equal to those of females. In 2021, DALYs and DALY rates of thalassemia in China displayed trends similar to the mortality rate (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). In 2021, the overall DALY rates of thalassemia among both sexes declined with increasing age, except for a transient rise in the 20\u0026ndash;24 and 40\u0026ndash;54 age groups. Among individuals under 45 years of age, males in 2021 had consistently higher DALY rates due to thalassemia than females of the same age, while the reverse pattern was observed among those aged 45 years and above.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e\u003cb\u003e3.3 China and global trend analysis of thalassemia\u003c/b\u003e\u003c/h2\u003e\u003cp\u003eTo further clarify the relative position of China in the global thalassemia burden, we compared the temporal trends of ASIR, ASPR, ASMR and ASDR in China with global trends from 1990 to 2021 (Table S2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In 2021, the number of incident cases of thalassemia in China accounted for 33.5% of the global total (Table S2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Notably, the ASIR of thalassemia in China in 2021 was 7.57 (95% UI: 5.53\u0026ndash;10.36) per 100,000 population, far surpassing the global ASIR of 1.93 (95% UI: 1.51\u0026ndash;2.49) per 100,000 population. The ASIR of thalassemia in China remained higher than the global level every year from 1990 to 2021. Although the ASIR of thalassemia in China demonstrated an overall declining trend from 1990 to 2021, it exhibited a consistent annual increase during the most recent five-year period (2017\u0026ndash;2021). Prevalent thalassemia cases in China represented 40.1% of the global total in 2021 (Table S2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Similar to the ASIR, the ASPR of thalassemia in China exceeded the global rate every year over the past 32 years. In 2021, deaths of thalassemia in China accounted for 16.8% of global cases (Table S2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). The ASMR of thalassemia in China declined steadily from 1990 to 2021 and remained equal to or below the global ASMR during the period from 2018 to 2021. The DALYs of thalassemia in China accounted for 14.3% of the global total in 2021 (Table S2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). Similar to the ASMR, the ASDR of thalassemia in China showed a consistent decline over the past 32 years and remained lower than the global ASDR from 2018 to 2021.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Trajectories in disease burden of thalassemia in China based on joinpoint regression analysis\u003c/h2\u003e\u003cp\u003eTo further clarify the temporal trends of thalassemia in China from 1990 to 2021, this study employed the joinpoint regression to quantify historical trajectories and identify joinpoints (Table S3, Table S4, and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Joinpoint regression analysis indicated that, between 1990 and 2021, the ASIR, ASMR, and ASDR of thalassemia in China declined overall, with AAPCs of -0.22% (95% CI: -0.34% to -0.10%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), -4.59% (95% CI: -4.77% to -4.40%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and \u0026minus;\u0026thinsp;4.74% (95% CI: -4.91% to -4.56%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively (Table S3 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB\u0026ndash;D). The ASPR of thalassemia in China showed no significant trend over the past 32 years, with an AAPC of -0.09% (95% CI: -0.18\u0026ndash;0.01%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.072) (Table S3 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Specifically, from 1990 to 2021, the ASIR of thalassemia in China exhibited a fluctuating trend (Table S4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). During the period from 2019 to 2021, the ASIR of thalassemia in China demonstrated an increasing trend (APC\u0026thinsp;=\u0026thinsp;3.43%, 95% CI: 2.08\u0026ndash;4.80%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), representing the highest rate of increase over the past 32 years. In sex-specific analyses, a joinpoint in 2019 marked a shift from decline to increase in ASIR for both males and females. Similar to both sexes, the greatest ASIR increases occurred between 2019 and 2021 in both males (APC\u0026thinsp;=\u0026thinsp;3.48%, 95% CI: 2.12\u0026ndash;4.86%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and females (APC\u0026thinsp;=\u0026thinsp;3.29%, 95% CI: 2.02\u0026ndash;4.58%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Regarding the ASPR in China, the most pronounced declines from 1990 to 2021 occurred during 2019 to 2021, with APCs of -4.68% (95% CI: -5.91% to -3.42%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), -4.85% (95% CI: -5.94% to -3.74%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and \u0026minus;\u0026thinsp;4.51% (95% CI: -5.95% to -3.06%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for both sexes, males, and females, respectively (Table S4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). From 1990 to 2021, the ASMR of thalassemia in China declined consistently across all periods (Table S4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). The greatest declines in ASMR occurred between 2009 and 2013, with APCs of -6.70% (95% CI: -7.60% to -5.79%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and \u0026minus;\u0026thinsp;6.90% (95% CI: -8.02% to -5.77%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for both sexes and males, respectively. In females, the largest decline in ASMR was observed between 2003 and 2006 (APC = -6.50%, 95% CI: -7.52% to -5.47%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, the ASDR of thalassemia in China declined throughout the period from 1990 to 2021 (Table S4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). The largest reductions in ASDR occurred between 2009 and 2014, with an APC of -6.67% (95% CI: -7.21% to -6.12%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for both sexes. In males and females, the greatest decline in ASDR was recorded during 2009\u0026ndash;2013 (APC = -7.10%, 95% CI: -8.14% to -6.05%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 2003\u0026ndash;2006 (APC = -6.68%, 95% CI: -8.13% to -5.21%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.5 The association between the burden of thalassemia and SDI in China\u003c/h2\u003e\u003cp\u003eWe assessed the association between the burden of thalassemia and SDI in China from 1990 to 2021 (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The results indicated a significant negative correlation between the ASIR of thalassemia and SDI (ρ= -0.842, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). A negative correlation was observed between the ASPR of thalassemia in China and the SDI (ρ = \u0026minus;\u0026thinsp;0.234, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.197), though this relationship did not achieve statistical significance (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). For ASMR (ρ= -1.000, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC) and ASDR (ρ= -1.000, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD), the burden of thalassemia in China demonstrated an almost perfect negative linear relationship with SDI from 1990 to 2021. These findings indicate that as SDI increases in China, both the ASMR and ASDR of thalassemia show a substantial decline.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.6 Changing trends in the prevalence of HF impairment with thalassemia in China\u003c/h2\u003e\u003cp\u003eHF due to iron overload is the most common and severe complication of thalassemia, significantly contributing to the overall disease burden[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, we further analyzed the number of prevalent cases and rates of HF impairment among individuals with thalassemia. In 2021, the absolute number of individuals with thalassemia combined with HF was highest in the \u0026lt;\u0026thinsp;5 age group, at 4,478.78 cases (95% UI: 2,877.33-6,753.44) (Table S5 and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eA), and the prevalence rate also peaked in this age group, reaching 5.77 per 100,000 population (95% UI: 3.70\u0026ndash;8.70). Overall, among individuals under 25 years of age in China, males bore a greater burden of thalassemia combined with HF than females, as evidenced by higher number of cases. However, this trend reversed among individuals aged 25 years and older. Regarding prevalence rates in 2021, both males and females with thalassemia combined with HF exhibited their highest rates in the \u0026lt;\u0026thinsp;5 age group: 6.64 per 100,000 population for males (95% UI: 4.29\u0026ndash;9.95) and 4.75 per 100,000 population for females (95% UI: 3.09\u0026ndash;7.15). Additionally, we applied joinpoint regression analysis to assess the temporal trends in the ASPR of thalassemia combined with HF in China from 1990 to 2021 (Table S6, Table S7, and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eB). Over the past 32 years, the ASPR of thalassemia combined with HF in both sexes and females showed an increasing trend, with AAPCs of 0.10% (95% CI: 0.01\u0026ndash;0.18%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) and 0.27% (95% CI: 0.19\u0026ndash;0.34%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively (Table S6 and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eB). In males, however, the ASPR of thalassemia combined with HF exhibited a declining trend, with an AAPC of -0.06% (95% CI: -0.10% to -0.02%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Notably, the period between 2000 and 2005 exhibited the greatest increases in ASPR for thalassemia combined with HF, with APCs of 5.06% (95% CI: 4.59\u0026ndash;5.53%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for both sexes, 4.40% (95% CI: 4.16\u0026ndash;4.64%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for males, and 6.04% (95% CI: 5.83\u0026ndash;6.25%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for females, respectively (Table S7 and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eB).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.7 Projections of thalassemia in China for the next 9 years\u003c/h2\u003e\u003cp\u003eWe employed the ARIMA model to project trends in the ASIR, ASPR, ASMR, and ASDR of thalassemia in China through 2030. The ASIR of thalassemia in China is projected to increase from 7.57 per 100,000 population in 2021 to 8.94 per 100,000 population in 2030 (Table S8 and Figure S2A). Similarly, the ASPR is expected to rise from 55.44 per 100,000 population in 2021 to 58.31 per 100,000 population in 2030, indicating an overall increase in the burden of thalassemia (Table S8 and Figure S2B). Conversely, both the ASMR and ASDR are projected to show significant declines. The ASMR and ASDR of thalassemia in China are expected to decrease from 0.15 and 11.11 per 100,000 population in 2021 to 0.08 and 6.18 per 100,000 population in 2030, respectively, reflecting ongoing improvements in thalassemia management in China (Table S8 and Figure S2C, D).\u003c/p\u003e\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study utilized the GBD 2021 dataset, analyzing incidence, prevalence, mortality, and DALYs to assess temporal trends in the burden of thalassemia in China and globally from 1990 to 2021. In 2021, countries ranked among the top ten for both the number of incident cases and the ASIR of thalassemia were predominantly located in Southeast Asia, including Cambodia, Laos, Thailand, Myanmar, Vietnam, and Timor-Leste. These findings are consistent with previous studies[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Among the most populous nations in the world, China recorded the highest number of new thalassemia cases in 2021 and was the only East Asian country to appear in the global top ten for both incident cases and ASIR, underscoring its considerable thalassemia burden. Similarly, for thalassemia trait, China reported the highest number of incident cases globally, with its ASIR ranking fifth worldwide. Collectively, these results emphasize that both thalassemia and thalassemia trait impose substantial public health challenges in China, necessitating focused attention from communities, healthcare professionals, and policymakers.\u003c/p\u003e\u003cp\u003ePrimary prevention based on carrier screening, genetic counseling and prenatal diagnosis are essential to reduce the risk of thalassemia‑affected births[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Several studies have demonstrated that large-scale population screening, combined with molecular techniques in South and Southwest China, has significantly reduced rates of birth defect among high-risk couples[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, the national incidence of thalassemia continues to fluctuate substantially. Specifically, between 2003 and 2011, China experienced the greatest decline in the ASIR of thalassemia. Yet, from 2019 to 2021, China observed the largest increase in the ASIR of thalassemia. We hypothesize that the observed fluctuations in the ASIR of thalassemia in China are closely linked to revisions in genetic disease screening policies at both national and subnational levels. At the national level, the Healthy China Initiative (2019\u0026ndash;2030) incorporated genetic disease screening into 15 major programs and called for a systematic enhancement of birth defect prevention and control capacity[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The subsequent Birth Defect Prevention and Control Capacity Improvement Plan (2023\u0026ndash;2027) set an ambitious target of achieving a prenatal screening rate of \u0026ge;\u0026thinsp;90% by 2027, with thalassemia identified as a key target for intervention, further driving the expansion of genetic screening and case registration across regions[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. At the provincial level, policies magnified this screening‑related ascertainment effect. In 2019, Guangxi implemented the Three-Year Action Plan for the Prevention and Control of Thalassemia in Guangxi (2019\u0026ndash;2021), providing free carrier screening and a \u0026ldquo;zero affected birth\u0026rdquo; intervention program for severe thalassemia to couples of reproductive age[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The program reached more than one million high-risk individuals over three years, thereby integrating numerous previously undiagnosed cases into the surveillance system and likely contributing substantially to the observed increase in the ASIR of thalassemia during this period. Moreover, the ASMR and ASDR of thalassemia in China consistently declined across all observed periods. This decline likely reflects the implementation of multilevel, optimized thalassemia management interventions. With the expansion of universal medical insurance coverage, increased drug reimbursement, adoption of emerging therapies such as gene editing, and the support of social organization, thalassemia management in China is transitioning from traditional transfusion and iron chelation to more comprehensive continuum-of-care models[\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThrough comparing the associations between the SDI and the thalassemia burden in China from 1990 to 2021, we found that lower levels of development were generally associated with a heavier burden across multiple indicators. This trend can primarily be attributed to inadequate early‑stage healthcare resources, such as the absence of screening programs, outdated diagnostic technologies, and poor treatment accessibility. From 1990 to 2021 in China, the increasing SDI in China paralleled a shift in molecular diagnostics for thalassemia, from liquid DNA\u0026ndash;DNA hybridization to next-generation sequencing (NGS)[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Regarding treatment, in addition to curative advances in hematopoietic stem cell transplantation, novel iron chelators, gene therapy agents, and CRISPR\u0026ndash;Cas9 gene editing techniques have the potential to improve management of patients with thalassemia and may reduce complications[\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. With the support of the 2015 Precision Poverty Alleviation policy and the Healthy China Initiative 2030, thalassemia prevention and control programs in ten high-prevalence provinces, autonomous regions, and municipalities, such as Guangxi, have made substantial progress[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. However, current thalassemia prevention and control programs remain concentrated in only a few southern provinces, and a comprehensive nationwide system has yet to be established. Future efforts should prioritize development of multifaceted strategies encompassing screening, prevention, treatment, public education, healthcare provider training, and the establishment of specialized centers and networks to reduce the disease burden of thalassemia across China.\u003c/p\u003e\u003cp\u003eIn terms of sex distribution, males generally bear a greater thalassemia burden. Disease burden data from China indicate that the ASDR for males was higher than that for females, both in 1990 and 2021. Among patients with severe thalassemia, cardiac disease remains the leading cause of death, accounting for 71% of fatalities, although survival rates have improved significantly with regular blood transfusions and iron chelation therapy[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Several studies have demonstrated that female thalassemia patients tend to have higher survival rates and a lower incidence of cardiac complications compared to male patients[\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. These sex‑specific patterns are consistent with our GBD 2021 findings. In 2021, the ASPR of thalassemia combined with HF was higher in males than in females, at 1.48 and 1.31 per 100,000 population, respectively. In β-thalassemia, pathways involved in oxidative stress defense, lipid metabolism, and erythropoietin activity show sex-related differences, although current evidence remains limited[\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Furthermore, regarding age distribution, thalassemia, a common monogenic disorder, predominantly affects children under the age of five. However, our study also identified a secondary peak in the ASMR and ASDR of thalassemia in individuals aged 50\u0026ndash;54 years in 2021. In China, the accelerating trend of population aging is likely to exacerbate this phenomenon. This shift in disease burden could have significant implications for healthcare resource allocation and social security systems, necessitating careful planning and policy adjustments.\u003c/p\u003e\u003cp\u003eThis study provides a comprehensive comparison of thalassemia characteristics in China and globally, revealing notable differences between China and other regions. To our knowledge, this GBD 2021\u0026ndash;based analysis of thalassemia burden in China represents the most comprehensive analysis to date, emphasizes the necessity of targeted interventions, and highlights key populations that should be prioritized. However, several limitations should be acknowledged. First, the GBD data are derived from cleaned and compiled reported sources, which are then adjusted through modeling techniques, rather than being directly derived from real‑world data collected in each country. This modeling approach may introduce estimation bias and uncertainty. Second, while there are significant regional disparities in prevalence of thalassemia across provinces in China, the GBD 2021 database lacks province-level (subnational) stratification, limiting the ability to conduct detailed subnational analyses. Finally, the lack of detailed differentiation between α- and β-thalassemia subtypes in the GBD 2021 data may have hindered the assessment of subtype-specific epidemiological patterns and disease burden.\u003c/p\u003e"},{"header":"5 Conclusions","content":"\u003cp\u003eThis study utilized GBD 2021 estimates to provide a comprehensive assessment of the thalassemia burden in China from 1990 to 2021. Although the ASMR and ASDR of thalassemia in China have generally decreased, the overall burden remains a significant public health challenge. Across sexes, the thalassemia burden is greater in males than in females. While advances in early screening and treatment have alleviated this burden to some extent, challenges from an aging demographic and large population base remain. Future initiatives should focus on equitable resource allocation, particularly in underserved and remote areas, by improving early screening, expanding health education, and optimizing treatment strategies to further reduce the thalassemia burden.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGBD Global Burden of Disease\u003c/p\u003e\u003cp\u003eASRs Age‑standardized rates\u003c/p\u003e\u003cp\u003eDALYs Disability‑adjusted life years\u003c/p\u003e\u003cp\u003eARIMA Autoregressive integrated moving average\u003c/p\u003e\u003cp\u003eASIR Age‑standardized incidence rate\u003c/p\u003e\u003cp\u003eASMR Age‑standardized mortality rate\u003c/p\u003e\u003cp\u003eASPR Age‑standardized prevalence rate\u003c/p\u003e\u003cp\u003eASDR Age‑standardized DALYs rate\u003c/p\u003e\u003cp\u003eEAPCs Estimated annual percentage changes\u003c/p\u003e\u003cp\u003eCODEm Cause of Death Ensemble model\u003c/p\u003e\u003cp\u003eST‑GPR Spatiotemporal Gaussian process regression\u003c/p\u003e\u003cp\u003eUIs Uncertainty intervals\u003c/p\u003e\u003cp\u003eCIs Confidence intervals\u003c/p\u003e\u003cp\u003eSDI Socio‑demographic index\u003c/p\u003e\u003cp\u003eAPC Annual percentage change\u003c/p\u003e\u003cp\u003eAAPC Average annual percentage change\u003c/p\u003e\u003cp\u003eADF Augmented Dickey\u0026ndash;Fuller test\u003c/p\u003e\u003cp\u003eACF Autocorrelation function\u003c/p\u003e\u003cp\u003ePACF Partial autocorrelation function\u003c/p\u003e\u003cp\u003eAIC Akaike Information Criterion\u003c/p\u003e\u003cp\u003eBIC Bayesian Information Criterion\u003c/p\u003e\u003cp\u003eNGS Next‑generation sequencing\u003c/p\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in this study are freely available from the Global Health Data Exchange (GHDx) website (http://ghdx.healthdata.org/gbd-results-tool). The datasets analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX.P. and X.B. analyzed the data, performed data visualization, and drafted the initial manuscript. S.G., W.W., L.T. and K.H. contributed to data collection and quality control. Y.S., F.Y., L.Z. and R.L. participated in the data preparation and verified the data. H.P., Z.G., W.L., J.Z., X.Y. reviewed and revised the manuscript. J.S. and Z.K. conceptualized the study, designed the manuscript framework, and supervised the project. All authors contributed to the work and approved the final version for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks to the Institute for Health Metrics and Evaluation (IHME) and the Global Burden of Disease study collaborations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the National Key R\u0026amp;D Program of China (2024YFC2510500), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, CIFMS (2024-I2M-ZH-021, 2022-I2M-2-003, 2021-I2M-1-073, 2023-I2M-2-007), the National Natural Science Foundation of China (82270145, 82300162, 82100145), and Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0037).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTaher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018;391(10116):155\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLal A, Vichinsky E. The Clinical Phenotypes of Alpha Thalassemia. Hematol Oncol Clin North Am. 2023;37(2):327\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet. 2022;399(10343):2310\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMusallam KM, Cappellini MD, Coates TD, Kuo KHM, Al-Samkari H, Sheth S, et al. Αlpha-thalassemia: A practical overview. Blood Rev. 2024;64:101165.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCasale M, Meloni A, Filosa A, Cuccia L, Caruso V, Palazzi G, et al. Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study. Circ Cardiovasc Imaging. 2015;8(8):e003230.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRivella S. β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica. 2015;100(4):418\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMusallam KM, Lombard L, Kistler KD, Arregui M, Gilroy KS, Chamberlain C, et al. Epidemiology of clinically significant forms of alpha- and beta-thalassemia: A global map of evidence and gaps. Am J Hematol. 2023;98(9):1436\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlint J, Hill AV, Bowden DK, Oppenheimer SJ, Sill PR, Serjeantson SW, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature. 1986;321(6072):744\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang WD, Hu F, Zhou DH, Gale RP, Lai YR, Yao HX, et al. Thalassaemia in China. Blood Rev. 2023;60:101074.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLai K, Huang G, Su L, He Y. The prevalence of thalassemia in mainland China: evidence from epidemiological surveys. Sci Rep. 2017;7(1):920.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGlobal incidence. prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u0026ndash;2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu P, Wang Y, Tian Z, Dong X, Li Z, Chen Y. Global, regional, and national burden of pancreatitis in children and adolescents. United Eur Gastroenterol J. 2025;13(3):376\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBai Z, Han J, An J, Wang H, Du X, Yang Z, et al. The global, regional, and national patterns of change in the burden of congenital birth defects, 1990\u0026ndash;2021: an analysis of the global burden of disease study 2021 and forecast to 2040. EClinicalMedicine. 2024;77:102873.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu Y, Xia F, Chen M, Zhang S, Yang Z, Gong Z, et al. Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024. BMC Public Health. 2023;23(1):122.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMeloni A, Pistoia L, Positano V, De Luca A, Martini N, Spasiano A, et al. Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major. Eur Radiol. 2023;33(2):1266\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePinto VM, Forni GL. Management of Iron Overload in Beta-Thalassemia Patients: Clinical Practice Update Based on Case Series. \u003cem\u003eInt J Mol Sci\u003c/em\u003e 2020, 21(22).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTuo Y, Li Y, Li Y, Ma J, Yang X, Wu S et al. Global, regional, and national burden of thalassemia, 1990\u0026ndash;2021: a systematic analysis for the global burden of disease study 2021. \u003cem\u003eEClinicalMedicine\u003c/em\u003e 2024, 72:102619.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIp HW, So CC. Diagnosis and prevention of thalassemia. Crit Rev Clin Lab Sci. 2013;50(6):125\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiao C, Zhou JY, Xie XM, Li DZ. Screening for Hb Constant Spring in the Guangdong Province, South China, using the Sebia capillary electrophoresis system. Hemoglobin. 2011;35(1):87\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin M, Wang Q, Zheng L, Huang Y, Lin F, Lin CP, et al. Prevalence and molecular characterization of abnormal hemoglobin in eastern Guangdong of southern China. Clin Genet. 2012;81(2):165\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHe J, Song W, Yang J, Lu S, Yuan Y, Guo J, et al. Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China. Genet Med. 2017;19(9):1022\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHealthy China Initiative. (2019\u0026ndash;2030) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.gov.cn/xinwen/2019-07/15/content_5409694.htm]\u003c/span\u003e\u003cspan address=\"http://www.gov.cn/xinwen/2019-07/15/content_5409694.htm]\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBirth Defect Prevention and Control Capacity Improvement Plan. (2023\u0026ndash;2027) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gov.cn/zhengce/zhengceku/202308/content_6900320.htm]\u003c/span\u003e\u003cspan address=\"https://www.gov.cn/zhengce/zhengceku/202308/content_6900320.htm]\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThree-Year Action Plan for the Prevention and Control of Thalassemia in Guangxi. (2019\u0026ndash;2021) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.gxzf.gov.cn/zwgk/zfxxgkzl_84988/zcwj_885018/xzgfxwj/t13714862.shtml]\u003c/span\u003e\u003cspan address=\"http://www.gxzf.gov.cn/zwgk/zfxxgkzl_84988/zcwj_885018/xzgfxwj/t13714862.shtml]\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeijing Angel Mother Charity Foundation CIoPW, Beijing Normal University: The Blue Book of Thalassemia in China: Investigation Report on the Prevention and Treatment of Thalassemia in China. (2020). Beijing: China Social Publishing House; 2021.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFu B, Liao J, Chen S, Li W, Wang Q, Hu J, et al. CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric β(0)/β(0) transfusion-dependent β-thalassemia. Nat Med. 2022;28(8):1573\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu R, Xu H, Liang J, Xie W, Yang G, Shi L, et al. Preliminary Result of the Safety and Efficacy of Autologous HBG1/2 Promoter-Modified CD34\u0026thinsp;+\u0026thinsp;Hematopoietic Stem and Progenitor Cells (RM-001) in Transfusion-Dependent Βeta-Thalassemia. Blood. 2022;140:4915\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang J, Yan J, Zeng F. Recent Progress on Genetic Diagnosis and Therapy for β-Thalassemia in China and Around the World. Hum Gene Ther. 2018;29(2):197\u0026ndash;203.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlgeri M, Lodi M, Locatelli F. Hematopoietic Stem Cell Transplantation in Thalassemia. Hematol Oncol Clin North Am. 2023;37(2):413\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsghar AA, Khabir Y, Hashmi MR. Zynteglo: Betibeglogene autotemcel - An innovative therapy for β- thalassemia patients. Ann Med Surg (Lond). 2022;82:104624.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCetin B, Erendor F, Eksi YE, Sanlioglu AD, Sanlioglu S. Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects. Expert Rev Mol Med. 2025;27:e16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTakpradit C, Viprakasit V, Narkbunnam N, Vathana N, Phuakpet K, Pongtanakul B, et al. Using of deferasirox and deferoxamine in refractory iron overload thalassemia. Pediatr Int. 2021;63(4):404\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThe 3 year action plan for prevention. and control of thalassemia in Guangxi [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.gxzf.gov.cn/zfgb/2019nzfgb/d9q_35420/zzqrmzfbgtwj_35422/t1514507.shtml]\u003c/span\u003e\u003cspan address=\"http://www.gxzf.gov.cn/zfgb/2019nzfgb/d9q_35420/zzqrmzfbgtwj_35422/t1514507.shtml]\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarsella M, Pepe A, Borgna-Pignatti C. Better survival and less cardiac morbidity in female patients with thalassemia major: a review of the literature. Ann N Y Acad Sci. 2010;1202:129\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBorgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89(10):1187\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChouliaras G, Yiannoutsos CT, Berdoukas V, Ladis V. Cardiac related death in thalassaemia major: time trend and risk factors in a large Greek Unit. Eur J Haematol. 2009;82(5):381\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTelfer PT, Warburton F, Christou S, Hadjigavriel M, Sitarou M, Kolnagou A, et al. Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone. Haematologica. 2009;94(12):1777\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKander MC, Cui Y, Liu Z. Gender difference in oxidative stress: a new look at the mechanisms for cardiovascular diseases. J Cell Mol Med. 2017;21(5):1024\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLink JC, Reue K. Genetic Basis for Sex Differences in Obesity and Lipid Metabolism. Annu Rev Nutr. 2017;37:225\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSoliz J, Khemiri H, Caravagna C, Seaborn T. Erythropoietin and the sex-dimorphic chemoreflex pathway. Adv Exp Med Biol. 2012;758:55\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[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":"Thalassemia, Global burden of disease, China, Joinpoint regression analysis, Epidemiological study","lastPublishedDoi":"10.21203/rs.3.rs-7350201/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7350201/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eChina accounts for the highest number of newly diagnosed thalassemia cases globally and harbors the largest population of thalassemia patients. However, its burden and disparities remain insufficiently characterized. To guide resource allocation and prevention strategies, this study analyzed the distribution and trends of thalassemia burden in China from 1990 to 2021.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe utilized data from the Global Burden of Disease (GBD) Study 2021 to assess the burden of thalassemia in China. This analysis involved estimating the absolute numbers and corresponding age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Additionally, we employed the autoregressive integrated moving average (ARIMA) model to forecast trends through 2030.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn 2021, China recorded the highest number of incident cases worldwide, with 40,143.5 cases (95% UI: 29,325.4\u0026ndash;54,927.5), and its age-standardized incidence rate (ASIR) was 7.6 (95% UI: 5.5\u0026ndash;10.4) per 100,000 population. From 1990 to 2021, both the ASIR and age-standardized mortality rate (ASMR) of thalassemia in China declined, with estimated annual percentage changes (EAPCs) of -0.60 (95% CI: -0.71 to -0.48) and \u0026minus;\u0026thinsp;4.90 (95% CI: -5.06 to -4.73), respectively. In 2021, the ASIR, age-standardized prevalence rate (ASPR), ASMR, and age-standardized DALYs rate (ASDR) of thalassemia in China were higher in males than females, and the incidence, prevalence, mortality, and DALY rates peaked in the \u0026lt;\u0026thinsp;5 age group for both sexes. Projections for the next 9 years indicate a steady decline in the ASMR and ASDR; however, the ASIR and ASPR are expected to rise further.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThalassemia represents a major public health challenge in China, with a persistently high disease burden. A pressing need exists to raise public awareness of the risk factors associated with thalassemia and to implement effective preventive strategies to reduce the future burden of this disorder.\u003c/p\u003e","manuscriptTitle":"Temporal trends in the disease burden of thalassemia in China from 1990 to 2021 and forecast to 2030","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 11:00:25","doi":"10.21203/rs.3.rs-7350201/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":"55429ed1-436a-41b4-80fb-cfa89144bbf1","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-17T14:09:00+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 11:00:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7350201","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7350201","identity":"rs-7350201","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}