jbm Journal of Biosciences and Medicines 2327-5081 2327-509X Scientific Research Publishing 10.4236/jbm.2024.1212029 jbm-138299 Articles Biomedical Life Sciences Global, Regional, and National Epidemiology of Thalassemia in Childhood from 1990 to 2021 Yongle Li 1 Wanshuo Wei 1 2 Yuan Gan 1 2 Xiaomei Xie 1 2 Pengtao Qin 1 2 Liangsen Teng 1 2 Lihe Jiang 1 3 aSchool of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, China aSchool of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China aKey Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou, China 02 12 2024 12 12 361 379 14, November 2024 17, November 2024 17, December 2024 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Objective: To analyze trends in prevalence, mortality, and disability-adjusted life years (DALYs) of childhood thalassemia from 1990 to 2021. Methods: Using the 2021 Global Burden of Disease (GBD) database, we conducted a cross-sectional study of children aged 0 - 14 years across 204 countries. We analyzed prevalence, mortality, and DALYs by region, country, age, sex, and Sociodemographic Index (SDI), calculating average annual percentage changes (EAPCs) to assess trends. Results: In 2021, there were 869,327 cases of childhood thalassemia globally. From 1990 to 2021, global prevalence decreased by 19.09%, and deaths declined from 12,018 to 5897. The mortality rate dropped from 0.69 to 0.29 per 100,000. High SDI regions had the lowest prevalence, mortality, and DALYs, all showing downward trends. Middle SDI regions had higher prevalence rates, while low and lower-middle SDI regions saw increases. Cambodia had the highest prevalence rate in 2021 (418 per 100,000), China had the highest number of cases (327,889), Pakistan had the highest DALYs (116987.40), and Guinea-Bissau had the highest DALYs rate (155.55 per 100,000). Conclusions: Childhood thalassemia remains a significant global health challenge. Despite declines in global prevalence, mortality, and DALYs, the burden remains high, especially in low SDI regions. Understanding the epidemiology of childhood thalassemia can aid in its prevention and control. Thalassemia Childhood Cross-Sectional Study 1. Introduction

Thalassemia is a group of inherited blood disorders that primarily affect the production of hemoglobin [1] [2] , leading to chronic anemia and other serious health issues. This condition not only causes patients to feel fatigued and weak but can also trigger a range of other severe health problems, such as heart disease, liver complications, and skeletal deformities [3] - [6] . Although the global burden of thalassemia has been somewhat alleviated, it remains a significant public health challenge in many regions. Pediatric thalassemia not only impacts the quality of life of patients but also imposes a heavy economic burden on families and society.

Early research focused mainly on the genetic basis and clinical manifestations of thalassemia. Studies found that thalassemia is caused by mutations in the hemoglobin genes, leading to insufficient or structurally abnormal hemoglobin production. With the advancement of molecular biology techniques, scientists have gained deeper insights into the mechanisms of these genetic mutations, thereby promoting progress in the diagnosis and treatment of thalassemia.

Additionally, significant advancements have been made in the research on treatments for thalassemia. Traditional treatment methods primarily include regular blood transfusions and iron chelation therapy to alleviate anemia and prevent complications caused by iron overload. In recent years, emerging technologies such as gene therapy and stem cell transplantation have offered hope for a cure for thalassemia. However, the high costs and complexity of these new technologies present challenges to their widespread adoption and application.

The Global Burden of Disease (GBD) study provides a comprehensive database for assessing the disease burden across different regions and countries [7] . By analyzing data from the GBD database, we can better understand the epidemiological characteristics of thalassemia at global, regional, and national levels. This is crucial for formulating effective public health policies and resource allocation strategies.

This study aims to analyze the trends in prevalence, mortality, and disability-adjusted life years (DALYs) of pediatric thalassemia from 1990 to 2021. By conducting a stratified analysis of data across different regions, countries, ages, genders, and SDI areas, we hope to uncover the epidemiological dynamics of thalassemia and provide scientific evidence for future prevention and control measures.

 2. Methods 2.1 Overview and Data Collection

Using the Global Health Data Exchange query tool created by GBD collaborators, we collected available data, standardized disease definitions, and prevalence information for children aged 0 to 14 years with thalassemia. The 2021 GBD study assessed the incidence, mortality, and DALYs of 371 diseases and injuries across 204 countries and regions from 1990 to 2021, with corresponding rates and uncertainty intervals, an increase from 369 in the 2019 edition. To summarize the age distribution of the burden of pediatric thalassemia, we categorized patients into three groups: under 5 years, 5 to 9 years, and 10 to 14 years. In this study, we collected data on the number of thalassemia cases and prevalence, thalassemia-related mortality, and the number of disability-adjusted life years related to pediatric thalassemia, along with their corresponding rates at global, regional, and national levels. Data on the race and ethnicity of participants were not listed in the GBD database, which does not allocate data collection by race and ethnicity.

 2.2. Sociodemographic Index

The Socio-demographic Index (SDI) is a measure of the development level of a country or region, based on data such as fertility rates, education levels, and per capita income [8] . The SDI ranges from 0 to 1, with higher levels indicating greater socio-economic development. It has been reported that SDI is associated with disease prevalence and mortality. This study categorizes countries and geographic regions into five SDI areas (low, lower-middle, middle, upper-middle, and high) to explore the relationship between the burden of pediatric thalassemia and socio-economic development.

 2.3. Statistical Analysis

Incidence, mortality, DALYs, and their corresponding rates are the main indicators describing the burden of pediatric diabetes. These rates are reported per 100,000 people [9] . All calculations were performed using R4.4.1. By calculating the Estimated Annual Percentage Change (EAPCs), the dynamics of pediatric diabetes were analyzed to determine the time trends of the disease burden. This is of great significance for the formulation of public health policies and resource allocation.

 3. Results 3.1. Global Trends in Childhood Thalassemia

Prevalence: In 2021, there were 869327.39 (708407.06 to 1065116.80) cases of thalassemia in children worldwide. Between 1990 and 2021, the global number of cases decreased by 6.41% (−5.37% to 7.22%). The corresponding prevalence decreased from 53.41 (44.59 to 64.11) in 1990 to 43.21 (35.21 to 52.94) in 2021. The prevalence of all children decreased with age ( Figure 1 ).

Deaths: In 2021, the global number of thalassemia-related deaths in children was 5897.44 (3884.59, 7892.94), compared to 12017.59 (8270.41, 16293.83) in 1990, a decrease of 50.92% (−76.15%, −4.56%). The highest number of deaths in 1990 and 2021 were among children under 5 years of age, 9226.19 (5721.01 to 13107.82) and 4236.48 (2868.08 to 5928.82) respectively ( Figure 1 ).

Disability-Adjusted Life Years (DALYs): Between 1990 and 2021, the number of thalassaemia-related disability-adjusted life years (DALYs) in children declined globally by about 50.08% (−74.60%, −4.29%). For both boys and girls, the older the age, the lower the incidence of DALYS ( Figure 1 ).

(a)--(b)--(c)--Figure 1. Trends in prevalence, mortality, and disability-adjusted life rate (DALYs) among children by age and sex. (a)--(b)--(c)--Figure 1. Trends in prevalence, mortality, and disability-adjusted life rate (DALYs) among children by age and sex. (a)--(b)--(c)--Figure 1. Trends in prevalence, mortality, and disability-adjusted life rate (DALYs) among children by age and sex. 3.2. Trends in SDI Regions for Pediatric Thalassemia

Prevalence: In 2021, the region with moderate SDI will have the highest number of cases of thalassemia in children, 388827.55 (314835.60 to 477709.51). The prevalence of High-middle SDI increased the most, to 463.67% (370.94 to 556.40). The prevalence of Middle SDI decreased the most, to −24.92% (−31.25 to 18.59). The largest decline was in the medium SDI region, with an EAPC of −0.86 (−1.17 to −0.56) ( Table 1 ).

<xref ref-type="bibr" rid="scirp.138299-"></xref>Table 1. Prevalence of thalassemia in children at global and regional levels, 1990-2021.

1990

2021

1990-2021

location_name

Prevalence number

Prevalence rate

Prevalence number

Prevalence rate

number change

EAPC

Global

928874.73 (775519.52 to 1115004.79)

53.41 (44.59 to 64.11)

869327.39 (708407.06 to 1065116.80)

43.21 (35.21 to 52.94)

−6.41% (−8.17 to −4.65)

−0.68% (−0.92 to −0.44)

High-middle SDI

20140.52 (108818.94 to 167381.63)

49.20 (39.77 to 61.17)

113563.87 (91269.60 to 139980.37)

49.19 (39.53 to 60.63)

463.67%

(370.94 to 556.40)

0.00% (0.00 to 0.00)

High SDI

20140.52 (16361.35 to 24144.83)

10.84 (8.81 to 12.99)

17695.77 (14588.18 to 21300.00)

10.25 (8.46 to 12.35)

−12.12% (−15.42 to −8.82)

−0.18% (−0.24 to −0.12)

Low-middle SDI

201655.35 (171767.32 to 239310.81)

42.71 (36.38 to 50.69)

234702.62 (186206.80 to 300237.05)

40.48 (32.11 to 51.78)

16.38% (13.29 to 19.47)

−0.17% (−0.23 to −0.11)

Low SDI

53858.82 (43132.75 to 68150.26)

23.53 (18.84 to 29.77)

113951.82 (90646.69 to 146121.46)

24.76 (19.70 to 31.75)

111.52% (90.91 to 132.13)

0.16% (0.11 to 0.22)

Middle SDI

518055.36 (424965.42 to 625614.89)

89.75 (73.62 to 108.39)

388827.55 (314835.60 to 477709.52)

68.60 (55.54 to 84.27)

−24.92% (−31.25 to −18.59)

−0.86% (−1.17 to −0.56)

Southeast Asia

190359.50 (166548.21 to 220681.45)

111.49 (97.54 to 129.24)

177089.80 (143399.16 to 219882.52)

102.57 (83.06 to 127.35)

−6.97% (−8.88 to −5.06)

−0.27% (−0.36 to −0.17)

East Asia

456514.89 (353394.66 to 579115.05)

138.41 (107.14 to 175.58)

331293.01 (255461.11 to 423058.03)

123.92 (95.55 to 158.24)

−27.45% (−34.97 to −19.93)

−0.36% (−0.48 to −0.23)

Oceania

1276.58 (995.82 to 1603.62)

47.64

(37.16 to 59.84)

2585.18 (2008.21 to 3218.58)

50.88 (39.52 to 63.35)

102.48% (83.98 to 120.98)

0.21% (0.14 to 0.29)

Central Europe

4341.71 (3356.07 to 5457.51)

14.73 (11.38 to 18.51)

2638.82 (2018.72 to 3359.18)

14.91 (11.40 to 18.98)

−39.23% (−49.98 to −28.48)

0.04% (0.03 to 0.05)

Eastern Europe

9102.90 (6850.61 to 11908.01)

17.69 (13.31 to 23.14)

6424.33 (4858.40 to 8339.46)

18.13 (13.71 to 23.53)

−29.42% (−37.47 to −21.37)

0.08%

(0.05 to 0.11)

Western Europe

8064.41 (6602.65 to 9523.50)

11.36 (9.30 to 13.41)

7195.03 (5936.52 to 8560.55)

10.56 (8.72 to 12.57)

−10.79% (−13.73 to −7.85)

−0.23% (−0.32 to −0.15)

Central Asia

5102.88 (4078.67 to 6311.21)

20.42 (16.32 to 25.25)

5674.85 (4513.41 to 7167.42)

20.50 (16.31 to 25.90)

11.21% (9.19 to 13.23)

0.01% (0.01 to 0.02)

Australasia

609.77

(462.22 to 785.51)

13.30 (10.08 to 17.13)

778.93 (583.91 to 1004.17)

13.59 (10.19 to 17.52)

27.74% (22.74 to 32.74)

0.07% (0.05 to 0.10)

Caribbean

2017.54 (1505.33 to 2599.75)

17.68 (13.19 to 22.78)

2390.71 (1793.70 to 3127.87)

20.78 (15.59 to 27.19)

18.51% (15.17 to 21.85)

0.52% (0.34 to 0.71)

Andean Latin America

2575.94 (1929.34 to 3429.03)

17.34

(12.99 to 23.09)

3518.80 (2600.92 to 4743.69)

19.45 (14.37 to 26.22)

36.61% (30.00 to 43.22)

0.37% (0.24 to 0.50)

High-income North America

2687.33 (2058.67 to 3464.33)

4.36 (3.34 to 5.62)

2014.03 (1692.45 to 2372.32)

3.07 (2.58 to 3.62)

−25.06% (−31.31 to −18.81)

−1.12% (−1.52 to −0.73)

High-income Asia Pacific

2814.38 (2255.24 to 3478.74)

8.00

(6.41 to 9.88)

1709.23 (1354.79 to 2131.59)

7.62 (6.04 to 9.51)

−39.27%

(−49.99 to −28.55)

−0.15% (−0.21 to −0.10)

North Africa and Middle East

48583.99 (39771.09 to 58789.84)

34.58 (28.31 to 41.85)

60086.87 (47730.51 to 74729.12)

32.78 (26.04 to 40.76)

23.68% (19.39 to 27.97)

−0.17% (−0.23 to −0.11)

Southern Latin America

724.67 (569.13 to 923.52)

4.85 (3.81 to 6.19)

684.42

(526.32 to 863.13)

4.72 (3.63 to 5.95)

−5.56%

(−7.08 to −4.04)

−0.09% (−0.12 to −0.06)

Tropical Latin America

8868.05 (6592.75 to 11553.21)

16.54 (12.30 to 21.55)

9774.18 (7289.84 to 12845.02)

19.47 (14.52 to 25.59)

10.20% (8.36 to 12.04)

0.53% (0.34 to 0.71)

Central Sub-Saharan Africa

5335.19 (3951.53 to 7209.70)

21.09 (15.62 to 28.50)

12565.46 (9195.91 to 16950.67)

21.41 (15.67 to 28.89)

135.51% (111.89 to 159.13)

0.05% (0.03 to 0.07)

Central Latin America

11744.93 (8735.45 to 15487.14)

18.24 (13.57 to 24.06)

13009.81 (9664.34 to 17083.80)

20.49 (15.22 to 26.91)

10.78% (8.83 to 12.73)

0.38% (0.24 to 0.51)

South Asia

119088.20 (101957.24 to 138808.71)

27.48 (23.53 to 32.03)

124230.98 (98494.68 to 158105.50)

24.50 (19.43 to 31.18)

4.32% (3.54 to 5.10)

−0.37% (−0.50 to −0.24)

Western Sub-Saharan Africa

21182.72 (16490.45 to 27184.96)

24.10 (18.76 to 30.93)

53050.43 (41321.14 to 68603.71)

24.70 (19.24 to 31.94)

150.45%

(124.12 to 176.78)

0.08% (0.05 to 0.11)

Southern Sub-Saharan Africa

5162.17 (3963.81 to 6797.87)

24.95 (19.16 to 32.86)

6322.60 (4883.98 to 8309.34)

26.27 (20.29 to 34.53)

22.47% (18.54 to 26.40)

0.17% (0.11 to 0.23)

Eastern Sub-Saharan Africa

22716.99 (17780.24 to 29585.02)

25.08

(19.63 to 32.67)

46289.92 (36087.34 to 60079.53)

25.94 (20.22 to 33.67)

103.77% (85.00 to 122.54)

0.11% (0.07 to 0.15)

Deaths: Mortality rates decreased in all five SDI regions. The greatest reduction in mortality was seen in the medium-high SDI region, at 85.17% (85.11% to 85.24%). In 2021, the regions with the highest SDI had the lowest number of deaths, at 17695.77 (14588.18 to 21300.00). The number of deaths decreased with increasing SDI, and the mortality rate decreased with increasing SDI ( Figure 2 ).

Disability-Adjusted Life Years (DALYs): In 2021, the number of DALYS will decrease with the increase of SDI, and the number of DALYS in low-SDI areas will be the highest, 220119.35 (146491.10 to 328060.66) ( Figure 2 ).

(a) (d)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId21.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId22.jpeg?20241220022211" /></p>(b) (e)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId23.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId24.jpeg?20241220022211" /></p>(c) (f)Figure 2. Prevalence, mortality, and disability-adjusted life rate (DALYs) in the five SDI regions in 2021. (a) (d)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId21.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId22.jpeg?20241220022211" /></p>(b) (e)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId23.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId24.jpeg?20241220022211" /></p>(c) (f)Figure 2. Prevalence, mortality, and disability-adjusted life rate (DALYs) in the five SDI regions in 2021. (a) (d)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId21.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId22.jpeg?20241220022211" /></p>(b) (e)<p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId23.jpeg?20241220022211" /></p> <p class="imgGroupCss_v"><img class=" imgMarkCss lazy" data-original="https://html.scirp.org/file/2152934-rId24.jpeg?20241220022211" /></p>(c) (f)Figure 2. Prevalence, mortality, and disability-adjusted life rate (DALYs) in the five SDI regions in 2021. 3.3. Regional Trends in Pediatric Thalassemia

Prevalence: In 2021, East Asia will have the largest number of thalassemia cases in children with 331293.01 (255461.11 to 423058.03), followed by Southeast Asia and South Asia. The lowest number of cases was recorded in Southern Latin America, at 778.93 (583.91 to 1004.17). The highest prevalence was also found in East Asia, at 123.92 (95.55 to 158.24), followed by Southeast Asia, at 102.57 (83.05 to 127.35) ( Figure 3 ). The largest downward trend in prevalence was in South Asia, with an EAPC of −0.37% (−0.50 to −0.24), and the largest upward trend was in Tropical Latin America, with an EAPC of 0.53% (0.34 to 0.71) ( Table 1 ).

Deaths: West sub-Saharan Africa will have the highest number of deaths in 2021, at 1634.70 (982.98 to 2572.78). Western sub-Saharan Africa has the highest mortality rate of 0.76 (0.46 to 1.20) and high-income North America has the lowest mortality rate of 0.006 (0.004 to 0.006) ( Figure 3 ). The largest decline in mortality was in East Asia, with an EAPC of −6.40 (−8.65 to −4.15) ( Table 1 ).

Disability-Adjusted Life Years (DALYs): In 2021, children in western sub-Saharan Africa will have the highest number of thalassemia-related disability-adjusted life years (DALYs) of 147743.57 (89487.17 to 231580.15), while children in western sub-Saharan Africa will also have the highest DALYS rate. For 68.79 (41.67 to 107.83) ( Figure 3 ). The decrease trend of DALYS rate was greatest in East Asia, with EAPC of −6.06 (−8.19 to −3.93) ( Table 1 ).

(a)--(b)--Figure 3. Comparison of prevalence, mortality rates, and disability-adjusted life year rates (DALYs) by region in 2021. (a)--(b)--Figure 3. Comparison of prevalence, mortality rates, and disability-adjusted life year rates (DALYs) by region in 2021. 3.4. National Trends in Pediatric Thalassemia

Prevalence: The country with the highest prevalence of thalassemia in children in 2021 is Cambodia, at 418.00 (312.89 to 543.84). The country with the highest number of cases is China, with 327888.97 (252513.83 to 419321.84). Brazil had the largest increase in Mediterranean cases in children, with an EAPC of 0.54 (0.72 to 0.35) ( Table 2 ). The largest decline was in the United States of America, with an EAPC of −1.29 (−1.74 to −0.84) ( Table 2 ).

Deaths: The highest number of thalassemia-related deaths in children in 2021 was in Pakistan, with 1360.96 (684.21 to 2175.62). The highest mortality rate was recorded in Guinea-Bissau, at 1.77 (0.36 to 9.34). The country with the largest increase in mortality was Tokelau, with an EAPC of 3.04 (1.97 to 4.11) ( Table 2 ). The largest reduction in mortality was seen in Grenada, with an EAPC of −15.97 (−21.59 to −10.35) ( Table 2 ).

Disability-Adjusted Life Years (DALYs): The highest number of DALYs in children with thalassemia in 2021 was in Pakistan, 116987.40 (59694.77 to 185535.93), and the highest DALYs rate was in Guinea-Bissau, 155.55 (32.67 to 816.01). Tokelau saw the largest increase in DALYs, with an EAPC of 2.76 (1.79 to 3.74) ( Table 2 ), and Saudi Arabia saw the largest decrease in DALYs, with an EAPC of −6.53 (−8.83 to −4.23) ( Table 2 ).

<xref ref-type="bibr" rid="scirp.138299-"></xref>Table 2. Estimated annual percentage change (EAPC) of prevalence, deaths, and disability-adjusted life years (DALYs) in 204 countries from 1990 to 2021.

Prevalence

Deaths

Disability-Adjusted Life Years (DALYs)

location_name

EAPC

CI_lower

CI_upper

EAPC

CI_lower

CI_upper

EAPC

CI_lower

CI_upper

Afghanistan

0.170218

0.110297

0.23014

−2.55291

−1.65422

−3.4516

−2.52507

−1.63618

−3.41396

Albania

−0.51335

−0.33264

−0.69406

−4.27884

−2.77257

−5.7851

−4.17647

−2.70624

−5.6467

Algeria

0.031286

0.020272

0.042299

−4.08565

−2.64739

−5.52391

−3.98942

−2.58504

−5.39381

American Samoa

−0.26952

−0.17464

−0.3644

−0.87094

−0.56435

−1.17754

−0.92591

−0.59997

−1.25186

Andorra

−0.10572

−0.0685

−0.14293

−5.85894

−3.79644

−7.92144

−5.09504

−3.30145

−6.88862

Angola

0.089335

0.057887

0.120784

−3.47077

−2.24897

−4.69257

−3.3601

−2.17726

−4.54295

Antigua and Barbuda

0.344536

0.22325

0.465822

−6.31432

−4.09152

−8.53713

−2.75138

−1.78282

−3.71994

Argentina

−0.10323

−0.06689

−0.13957

−4.7893

−3.10334

−6.47526

−4.53667

−2.93964

−6.13369

Armenia

−0.11213

−0.07266

−0.1516

−3.16591

−2.05143

−4.28039

−2.80697

−1.81884

−3.79509

Australia

0.061217

0.039667

0.082767

−4.02898

−2.61067

−5.44728

−3.43595

−2.2264

−4.64549

Austria

−0.07389

−0.04788

−0.09991

−4.38459

−2.8411

−5.92808

−2.95896

−1.91733

−4.00059

Azerbaijan

−0.48156

−0.31204

−0.65108

−3.44045

−2.22932

−4.65158

−3.43945

−2.22867

−4.65023

Bahamas

0.330827

0.214367

0.447287

−5.68682

−3.68491

−7.68873

−0.57873

−0.375

−0.78246

Bahrain

−0.26867

−0.17409

−0.36324

−4.12362

−2.672

−5.57524

−4.04265

−2.61953

−5.46578

Bangladesh

0.036825

0.023862

0.049789

−4.0026

−2.59358

−5.41161

−3.55812

−2.30557

−4.81067

Barbados

0.370646

0.240169

0.501123

−5.45277

−3.53325

−7.37229

−2.98505

−1.93423

−4.03587

Belarus

0.161614

0.104722

0.218506

−0.29197

−0.18919

−0.39475

−0.5479

−0.35502

−0.74077

Belgium

−0.11968

−0.07755

−0.16181

−3.93662

−2.55083

−5.32242

−3.27254

−2.12052

−4.42456

Belize

0.305624

0.198036

0.413211

−2.80999

−1.8208

−3.79918

−1.96426

−1.27279

−2.65573

Cenin

0.162752

0.105459

0.220045

−3.07721

−1.99395

−4.16047

−3.03781

−1.96842

−4.10719

Bermuda

0.359475

0.23293

0.48602

−0.69151

−0.44808

−0.93493

−0.46359

−0.30039

−0.62678

Bhutan

−0.15709

−0.10179

−0.21239

−3.02005

−1.95691

−4.08319

−2.87932

−1.86572

−3.89292

Bolivia (Plurinational State of)

0.270249

0.175114

0.365383

−4.07089

−2.63783

−5.50396

−3.96439

−2.56882

−5.35996

Bosnia and Herzegovina

−0.07009

−0.04542

−0.09477

−4.35461

−2.82167

−5.88754

−3.70594

−2.40135

−5.01053

Botswana

0.159813

0.103555

0.216072

−0.23516

−0.15238

−0.31795

−0.22931

−0.14859

−0.31003

Brazil

0.535117

0.346742

0.723492

−3.34395

−2.16679

−4.52111

−1.72355

−1.11682

−2.33029

Brunei Darussalam

−0.24114

−0.15625

−0.32602

−2.25985

−1.46432

−3.05537

−2.15081

−1.39367

−2.90795

Bulgaria

0.125999

0.081644

0.170354

−2.70934

−1.75558

−3.66309

−2.29153

−1.48485

−3.09821

Burkina Faso

0.203144

0.131632

0.274657

−1.80102

−1.16702

−2.43503

−1.76441

−1.14329

−2.38553

Burundi

0.183328

0.118792

0.247864

−2.81994

−1.82724

−3.81263

−2.77485

−1.79803

−3.75168

Cabo Verde

0.088426

0.057297

0.119554

−3.72457

−2.41342

−5.03572

−3.66231

−2.37308

−4.95153

Cambodia

0.244668

0.158538

0.330797

−3.03595

−1.96721

−4.10468

−2.55188

−1.65355

−3.45021

Cameroon

0.058857

0.038138

0.079577

−1.63004

−1.05623

−2.20386

−1.62161

−1.05076

−2.19246

Canada

−0.29016

−0.18802

−0.3923

−3.41945

−2.21571

−4.62318

−3.03546

−1.9669

−4.10403

Central African Republic

0.038935

0.025229

0.052642

−1.72244

−1.1161

−2.32879

−1.69786

−1.10017

−2.29556

Chad

0.162012

0.104979

0.219044

−1.12882

−0.73145

−1.5262

−1.12625

−0.72978

−1.52271

Chile

−0.09239

−0.05987

−0.12492

−4.57128

−2.96207

−6.18049

−3.63557

−2.35575

−4.91539

China

−0.37524

−0.24315

−0.50734

−6.49132

−4.2062

−8.77643

−6.14163

−3.97962

−8.30365

Colombia

0.382675

0.247964

0.517387

−2.15914

−1.39906

−2.91921

−1.19543

−0.77461

−1.61625

Comoros

0.260092

0.168533

0.351652

−1.93084

−1.25113

−2.61054

−1.92548

−1.24766

−2.60329

Congo

0.069769

0.045208

0.094329

−3.07016

−1.98938

−4.15093

−3.01212

−1.95178

−4.07247

Cook Islands

−0.14772

−0.09572

−0.19972

−3.07814

−1.99455

−4.16172

−2.73506

−1.77225

−3.69788

Costa Rica

0.355697

0.230482

0.480912

−3.68081

−2.38507

−4.97655

−1.78482

−1.15652

−2.41312

Croatia

0.196236

0.127156

0.265317

−2.88127

−1.86699

−3.89555

−1.28657

−0.83366

−1.73947

Cuba

0.326069

0.211284

0.440854

−6.36912

−4.12702

−8.61122

−2.41624

−1.56566

−3.26682

Cyprus

−0.46801

−0.30326

−0.63276

−5.31048

−3.44105

−7.17991

−4.60229

−2.98216

−6.22242

Czechia

0.291336

0.188778

0.393893

−2.92673

−1.89644

−3.95702

−1.18238

−0.76615

−1.59861

Côte d’Ivoire

0.021971

0.014237

0.029706

−1.83047

−1.1861

−2.47485

−1.79856

−1.16542

−2.4317

Democratic People’s Republic of Korea

−0.17227

−0.11163

−0.23291

−3.05248

−1.97793

−4.12704

−2.99281

−1.93926

−4.04636

Democratic Republic of the Congo

0.040429

0.026197

0.054661

−2.51556

−1.63002

−3.40111

−2.47334

−1.60266

−3.34403

Denmark

0.000503

0.000326

0.000679

−3.45851

−2.24102

−4.67599

−2.56248

−1.66042

−3.46454

Djibouti

0.247051

0.160082

0.334019

−2.32935

−1.50936

−3.14935

−2.27817

−1.47619

−3.08014

Dominica

0.255508

0.165563

0.345454

0.282006

0.182732

0.381279

0.243374

0.1577

0.329048

Dominican Republic

0.383351

0.248401

0.5183

−2.50206

−1.62127

−3.38285

−2.41598

−1.56549

−3.26646

Ecuador

0.337007

0.218372

0.455643

−5.85323

−3.79274

−7.91372

−0.30902

−0.20024

−0.4178

Egypt

0.049325

0.031961

0.066688

−2.94725

−1.90974

−3.98476

−2.84916

−1.84618

−3.85214

El Salvador

0.407579

0.264101

0.551058

−3.95048

−2.5598

−5.34115

−3.89837

−2.52604

−5.27069

Equatorial Guinea

−0.10676

−0.06918

−0.14434

−3.98247

−2.58054

−5.38441

−3.73219

−2.41836

−5.04602

Eritrea

0.242748

0.157294

0.328201

−1.19277

−0.77289

−1.61266

−1.17089

−0.7587

−1.58307

Estonia

0.130941

0.084846

0.177035

−3.63243

−2.35372

−4.91114

−1.05044

−0.68066

−1.42022

Eswatini

0.13911

0.090139

0.18808

−0.71634

−0.46417

−0.9685

−0.70981

−0.45994

−0.95968

Ethiopia

0.156291

0.101273

0.21131

−3.27518

−2.12223

−4.42813

−3.21296

−2.08191

−4.344

Fiji

−0.03636

−0.02356

−0.04915

−0.14878

−0.0964

−0.20115

−0.15912

−0.1031

−0.21513

Finland

−0.11288

−0.07315

−0.15262

−2.64416

−1.71334

−3.57497

−1.42202

−0.92143

−1.9226

France

−0.13961

−0.09047

−0.18876

−3.79923

−2.4618

−5.13666

−3.00974

−1.95023

−4.06925

Gabon

0.039713

0.025733

0.053693

−2.21053

−1.43237

−2.9887

−2.15485

−1.39628

−2.91341

Gambia

0.11011

0.071348

0.148872

−2.04251

−1.32349

−2.76153

−2.02418

−1.31161

−2.73674

Georgia

0.458016

0.296782

0.619249

−0.12358

−0.08008

−0.16708

−0.05934

−0.03845

−0.08022

Germany

0.285636

0.185084

0.386187

−3.13866

−2.03377

−4.24355

−2.71519

−1.75937

−3.67101

Ghana

0.112561

0.072937

0.152186

−2.43627

−1.57864

−3.2939

−2.41455

−1.56457

−3.26454

Greece

−0.19738

−0.1279

−0.26686

−4.64633

−3.0107

−6.28197

−4.18552

−2.71211

−5.65893

Greenland

−0.00625

−0.00405

−0.00845

−2.51848

−1.63191

−3.40505

−2.2523

−1.45943

−3.04517

Grenada

0.298026

0.193113

0.402939

−15.9666

−10.346

−21.5873

−5.4256

−3.51565

−7.33556

Guam

−0.11995

−0.07772

−0.16217

−4.45737

−2.88826

−6.02649

−3.19685

−2.07148

−4.32223

Guatemala

0.280187

0.181554

0.37882

−2.86716

−1.85785

−3.87648

−1.20982

−0.78393

−1.63571

Guinea

0.039306

0.025469

0.053143

−2.13575

−1.38391

−2.88759

−2.1127

−1.36897

−2.85643

Guinea-Bissau

0.244126

0.158187

0.330065

−2.96593

−1.92184

−4.01001

−2.96386

−1.9205

−4.00722

Guyana

0.18539

0.120128

0.250652

−7.20253

−4.66705

−9.73801

−5.52435

−3.57964

−7.46907

Haiti

0.35156

0.227802

0.475319

−1.35936

−0.88083

−1.83788

−1.34337

−0.87047

−1.81627

Honduras

0.462596

0.29975

0.625441

−4.20443

−2.72436

−5.6845

−4.15599

−2.69297

−5.61901

Hungary

0.263448

0.170708

0.356189

−2.47497

−1.60372

−3.34623

−1.316

−0.85273

−1.77926

Iceland

−0.06933

−0.04493

−0.09374

−2.63397

−1.70675

−3.5612

−0.56753

−0.36775

−0.76732

India

−0.25221

−0.16342

−0.34099

−3.74366

−2.42579

−5.06153

−3.41545

−2.21312

−4.61777

Indonesia

0.356334

0.230895

0.481773

−2.40675

−1.55951

−3.254

−2.35198

−1.52402

−3.17994

Iran (Islamic Republic of)

−0.16318

−0.10574

−0.22063

−6.08388

−3.94219

−8.22557

−5.87132

−3.80446

−7.93818

Iraq

−0.19895

−0.12892

−0.26899

−4.25355

−2.75619

−5.75091

−4.08231

−2.64523

−5.51939

Ireland

−0.0355

−0.023

−0.04799

−4.7873

−3.10205

−6.47256

−2.98131

−1.93181

−4.0308

Israel

−0.18687

−0.12108

−0.25265

−4.9029

−3.17695

−6.62885

−4.53006

−2.93536

−6.12476

Italy

0.099508

0.064478

0.134537

−5.02816

−3.25811

−6.7982

−4.25203

−2.7552

−5.74886

Jamaica

0.344643

0.22332

0.465967

−4.88671

−3.16646

−6.60695

−0.82323

−0.53343

−1.11303

Japan

−0.07542

−0.04887

−0.10196

−5.58619

−3.61971

−7.55268

−4.55898

−2.9541

−6.16387

Jordan

−0.37765

−0.24471

−0.51059

−3.72181

−2.41163

−5.03198

−3.60248

−2.33431

−4.87064

Kazakhstan

0.21118

0.136839

0.285521

1.675702

1.08581

2.265593

0.880589

0.570598

1.190579

Kenya

0.015631

0.010129

0.021134

−1.45025

−0.93973

−1.96078

−1.38057

−0.89457

−1.86656

Kiribati

−0.18651

−0.12085

−0.25216

−2.13484

−1.38332

−2.88636

−2.14768

−1.39164

−2.90372

Kuwait

0.122793

0.079567

0.166019

−1.53316

−0.99344

−2.07287

−1.40504

−0.91043

−1.89966

Kyrgyzstan

0.062663

0.040604

0.084722

−1.73343

−1.12322

−2.34364

−1.25914

−0.81589

−1.7024

Lao People’s Democratic Republic

0.368667

0.238887

0.498448

−2.86792

−1.85833

−3.8775

−2.50646

−1.62412

−3.3888

Latvia

0.133543

0.086532

0.180553

−3.81046

−2.46908

−5.15184

−0.94058

−0.60947

−1.27169

Lebanon

−0.31344

−0.2031

−0.42378

−4.076

−2.64114

−5.51085

−3.8712

−2.50844

−5.23396

Lesotho

0.076365

0.049483

0.103248

0.24538

0.159

0.33176

0.202346

0.131115

0.273577

Liberia

−0.12625

−0.08181

−0.1707

−3.62826

−2.35102

−4.9055

−3.58231

−2.32124

−4.84338

Libya

−0.23095

−0.14965

−0.31224

−2.8158

−1.82457

−3.80704

−2.5745

−1.66821

−3.48079

Lithuania

0.154333

0.100004

0.208663

−2.54075

−1.64634

−3.43516

−0.99802

−0.64669

−1.34935

Luxembourg

0.026007

0.016852

0.035163

−5.67825

−3.67936

−7.67715

−3.94855

−2.55856

−5.33854

Madagascar

0.05389

0.034919

0.072861

−2.4182

−1.56693

−3.26947

−2.37262

−1.5374

−3.20785

Malawi

−0.02782

−0.01803

−0.03762

−3.61149

−2.34015

−4.88283

−3.57779

−2.31831

−4.83727

Malaysia

−0.24434

−0.15833

−0.33035

−3.7788

−2.44856

−5.10904

−3.48574

−2.25867

−4.71282

Maldives

−0.38681

−0.25064

−0.52298

−4.41996

−2.86402

−5.97591

−4.00258

−2.59357

−5.4116

Mali

0.11595

0.075133

0.156768

−2.46085

−1.59457

−3.32714

−2.43373

−1.57699

−3.29047

Malta

0.258578

0.167552

0.349604

−1.36291

−0.88313

−1.84269

−1.34154

−0.86928

−1.8138

Marshall Islands

−0.10118

−0.06556

−0.13679

−1.11272

−0.72101

−1.50443

−1.04566

−0.67756

−1.41377

Mauritania

0.063963

0.041446

0.086479

−2.73198

−1.77025

−3.69371

−2.69669

−1.74739

−3.646

Mauritius

0.083588

0.054163

0.113013

−0.8354

−0.54131

−1.12948

−0.7504

−0.48624

−1.01457

Mexico

0.353346

0.228959

0.477733

−1.95493

−1.26674

−2.64311

−0.96373

−0.62447

−1.30299

Micronesia (Federated States of)

−0.11412

−0.07395

−0.15429

−3.07444

−1.99216

−4.15672

−2.7936

−1.81018

−3.77702

Monaco

−0.15681

−0.10161

−0.21201

−3.06168

−1.98388

−4.13947

−2.71358

−1.75833

−3.66883

Mongolia

0.221198

0.143331

0.299066

−3.75487

−2.43306

−5.07668

−3.66229

−2.37307

−4.95151

Montenegro

0.196391

0.127256

0.265526

−3.90018

−2.52722

−5.27315

−3.32877

−2.15696

−4.50059

Morocco

−0.1356

−0.08786

−0.18333

−4.24457

−2.75037

−5.73877

−4.15213

−2.69047

−5.61379

Mozambique

0.269815

0.174833

0.364797

−2.64133

−1.71151

−3.57115

−2.6107

−1.69166

−3.52973

Myanmar

0.451772

0.292736

0.610808

−2.59999

−1.68473

−3.51526

−2.36328

−1.53134

−3.19522

Namibia

0.148105

0.095968

0.200242

−0.82498

−0.53457

−1.1154

−0.81994

−0.5313

−1.10857

Nauru

−0.1269

−0.08223

−0.17157

−1.50752

−0.97683

−2.0382

−1.42567

−0.9238

−1.92754

Nepal

−0.05534

−0.03586

−0.07482

−4.47118

−2.89721

−6.04516

−4.28733

−2.77807

−5.79658

Netherlands

−0.02075

−0.01345

−0.02805

−4.64474

−3.00967

−6.27981

−3.96624

−2.57002

−5.36246

New Zealand

0.117875

0.07638

0.15937

−5.22238

−3.38396

−7.06079

−3.52951

−2.28703

−4.77199

Nicaragua

0.401501

0.260162

0.54284

−4.87199

−3.15692

−6.58705

−4.79715

−3.10843

−6.48588

Niger

0.159297

0.10322

0.215374

−3.48219

−2.25637

−4.70802

−3.39825

−2.20198

−4.59453

Nigeria

0.120131

0.077841

0.16242

−0.96904

−0.62792

−1.31017

−0.9601

−0.62212

−1.29808

Niue

−0.1519

−0.09843

−0.20537

2.680798

1.737087

3.62451

2.430342

1.574797

3.285887

North Macedonia

0.054668

0.035424

0.073913

−6.06841

−3.93217

−8.20465

−5.5231

−3.57882

−7.46738

Northern Mariana Islands

−0.19437

−0.12595

−0.26279

−4.14285

−2.68446

−5.60125

−2.86039

−1.85346

−3.86732

Norway

−0.17824

−0.11549

−0.24098

−6.21472

−4.02697

−8.40246

−2.79766

−1.81281

−3.78251

Oman

−0.11004

−0.0713

−0.14878

−4.15492

−2.69228

−5.61756

−3.97191

−2.57369

−5.37013

Pakistan

−0.71218

−0.46148

−0.96289

−0.83077

−0.53832

−1.12322

−0.85213

−0.55216

−1.15211

Palau

−0.13323

−0.08633

−0.18013

−2.93337

−1.90075

−3.966

−2.60676

−1.68911

−3.52441

Palestine

−0.2321

−0.15039

−0.3138

−3.90237

−2.52863

−5.27611

−3.78636

−2.45346

−5.11925

Panama

0.423043

0.274121

0.571966

−2.11983

−1.3736

−2.86607

−1.52202

−0.98623

−2.05781

Papua New Guinea

0.113215

0.07336

0.153069

−1.20233

−0.77908

−1.62559

−1.10972

−0.71907

−1.50037

Paraguay

0.358985

0.232613

0.485357

−1.51917

−0.98438

−2.05395

−1.48263

−0.96071

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Peru

0.410729

0.266142

0.555317

−4.66966

−3.02582

−6.3135

−4.49158

−2.91043

−6.07274

Philippines

0.062479

0.040485

0.084473

−2.59659

−1.68252

−3.51066

−2.5658

−1.66257

−3.46903

Poland

−0.06242

−0.04044

−0.08439

−6.38559

−4.1377

−8.63349

−2.51257

−1.62808

−3.39705

Portugal

−0.10047

−0.0651

−0.13584

−5.7661

−3.73628

−7.79592

−5.07526

−3.28863

−6.86188

Puerto Rico

0.344741

0.223383

0.466099

−6.33121

−4.10245

−8.55996

−0.45034

−0.29181

−0.60887

Qatar

−0.1634

−0.10588

−0.22093

−5.19144

−3.36392

−7.01896

−4.62996

−3.00009

−6.25983

Republic of Korea

−0.13587

−0.08804

−0.18371

−6.38072

−4.13454

−8.62691

−5.93062

−3.84289

−8.01836

Republic of Moldova

0.098613

0.063899

0.133328

−1.96621

−1.27405

−2.65836

−1.55547

−1.00791

−2.10304

Romania

0.209643

0.135843

0.283443

−4.60025

−2.98084

−6.21965

−3.48517

−2.2583

−4.71205

Russian Federation

0.068319

0.044269

0.09237

−2.08746

−1.35262

−2.8223

−1.50768

−0.97694

−2.03842

Rwanda

0.199902

0.129531

0.270272

−3.13351

−2.03043

−4.23658

−3.09365

−2.0046

−4.18269

Saint Kitts and Nevis

0.381153

0.246977

0.515329

−1.55503

−1.00762

−2.10244

−0.82187

−0.53255

−1.1112

Saint Lucia

0.35708

0.231379

0.482782

0.822003

0.532636

1.11137

−0.21515

−0.13941

−0.29089

Saint Vincent and the Grenadines

0.396145

0.256692

0.535599

−5.30559

−3.43788

−7.17329

−1.387

−0.89874

−1.87526

Samoa

−0.03592

−0.02327

−0.04856

−2.68799

−1.74175

−3.63424

−2.40809

−1.56038

−3.25581

San Marino

0.203516

0.131873

0.275159

−5.17

−3.35002

−6.98997

−4.02948

−2.611

−5.44796

Sao Tome and Principe

0.096626

0.062611

0.130641

−4.4681

−2.89521

−6.04099

−4.36644

−2.82934

−5.90355

Saudi Arabia

−0.13337

−0.08642

−0.18032

−6.92187

−4.48519

−9.35855

−6.53282

−4.23309

−8.83254

Senegal

0.118371

0.076701

0.160041

−2.67114

−1.73083

−3.61145

−2.63775

−1.7092

−3.56631

Serbia

0.091993

0.059609

0.124378

−6.45049

−4.17975

−8.72124

−5.67919

−3.67997

−7.67842

Seychelles

−0.01591

−0.01031

−0.0215

−2.8354

−1.83726

−3.83354

−2.59127

−1.67908

−3.50347

Sierra Leone

0.015863

0.010279

0.021447

−2.06853

−1.34035

−2.79671

−2.03977

−1.32172

−2.75782

Singapore

−0.3149

−0.20405

−0.42576

−6.79255

−4.40139

−9.1837

−6.26825

−4.06166

−8.47484

Slovakia

0.134213

0.086966

0.181459

−3.65713

−2.36972

−4.94453

−3.03051

−1.96369

−4.09733

Slovenia

0.211908

0.137311

0.286505

−3.23689

−2.09742

−4.37636

−1.19727

−0.7758

−1.61874

Solomon Islands

−0.11087

−0.07184

−0.1499

−2.06569

−1.33851

−2.79286

−1.88798

−1.22336

−2.5526

Somalia

0.375828

0.243526

0.508129

−1.55438

−1.0072

−2.10157

−1.51961

−0.98467

−2.05456

South Africa

0.134444

0.087116

0.181772

−1.37917

−0.89367

−1.86468

−1.32342

−0.85754

−1.7893

South Sudan

0.14857

0.096269

0.200871

−0.72489

−0.46971

−0.98007

−0.74011

−0.47957

−1.00065

Spain

0.079167

0.051298

0.107036

−3.91345

−2.53581

−5.29109

−3.40917

−2.20905

−4.60929

Sri Lanka

0.139718

0.090533

0.188902

−5.16692

−3.34803

−6.98581

−4.86851

−3.15466

−6.58235

Sudan

−0.12625

−0.08181

−0.17069

−4.11449

−2.66608

−5.5629

−4.03723

−2.61602

−5.45845

Suriname

0.398284

0.258077

0.53849

−1.77719

−1.15157

−2.40281

−1.71442

−1.1109

−2.31794

Sweden

−0.03025

−0.0196

−0.0409

−3.99796

−2.59057

−5.40534

−2.77601

−1.79878

−3.75324

Switzerland

0.007796

0.005052

0.010541

−3.86175

−2.50231

−5.22119

−3.25456

−2.10887

−4.40026

Syrian Arab Republic

−0.48379

−0.31348

−0.6541

−3.99448

−2.58832

−5.40064

−3.98334

−2.5811

−5.38558

Taiwan (Province of China)

0.506712

0.328336

0.685087

1.75767

1.138924

2.376416

1.566251

1.014889

2.117613

Tajikistan

−0.29219

−0.18933

−0.39505

−2.37294

−1.5376

−3.20828

−2.31801

−1.50201

−3.13401

Thailand

−0.1348

−0.08735

−0.18226

−6.54808

−4.24299

−8.85318

−5.11143

−3.31207

−6.91078

Timor-Leste

−0.13564

−0.08789

−0.18339

−2.82754

−1.83217

−3.82291

−2.77763

−1.79983

−3.75543

Togo

0.149509

0.096878

0.20214

−2.31728

−1.50154

−3.13302

−2.28878

−1.48307

−3.0945

Tokelau

−0.19051

−0.12344

−0.25757

3.040014

1.969849

4.110179

2.762699

1.790156

3.735242

Tonga

−0.04111

−0.02664

−0.05558

−1.9049

−1.23433

−2.57548

−1.67722

−1.0868

−2.26765

Trinidad and Tobago

0.278181

0.180254

0.376108

−3.46309

−2.24399

−4.68219

−3.05107

−1.97701

−4.12512

Tunisia

−0.32138

−0.20825

−0.43452

−4.9349

−3.19768

−6.67211

−4.72614

−3.06241

−6.38987

Turkey

0.010793

0.006994

0.014592

−5.63985

−3.65447

−7.62522

−5.515

−3.57357

−7.45642

Turkmenistan

0.113876

0.073789

0.153964

1.217122

0.788663

1.645581

0.900771

0.583676

1.217867

Tuvalu

−0.25877

−0.16768

−0.34987

−4.18363

−2.71088

−5.65638

−3.93227

−2.54801

−5.31653

Uganda

0.035603

0.02307

0.048136

−1.80192

−1.16759

−2.43624

−1.79574

−1.16359

−2.42789

Ukraine

−0.00764

−0.00495

−0.01033

−2.81711

−1.82542

−3.80881

−2.41827

−1.56698

−3.26957

United Arab Emirates

−0.50211

−0.32535

−0.67887

−5.24413

−3.39806

−7.09021

−4.81269

−3.11849

−6.50688

United Kingdom

−0.07014

−0.04545

−0.09483

−0.03996

−0.02589

−0.05402

−0.07336

−0.04754

−0.09919

United Republic of Tanzania

0.084599

0.054818

0.11438

−1.60547

−1.0403

−2.17064

−1.6095

−1.04291

−2.17608

United States of America

−1.28956

−0.8356

−1.74352

−3.82361

−2.4776

−5.16962

−3.63334

−2.35431

−4.91237

United States Virgin Islands

0.419905

0.272087

0.567722

−4.2334

−2.74313

−5.72367

−3.56291

−2.30867

−4.81715

Uruguay

−0.13219

−0.08566

−0.17873

−4.67974

−3.03235

−6.32713

−4.358

−2.82387

−5.89213

Uzbekistan

−0.02777

−0.01799

−0.03754

0.083683

0.054225

0.113142

−0.01858

−0.01204

−0.02512

Vanuatu

−0.11695

−0.07578

−0.15811

−1.79795

−1.16502

−2.43087

−1.60628

−1.04083

−2.17174

Venezuela (Bolivarian Republic of)

0.428484

0.277646

0.579322

−1.3434

−0.87049

−1.81631

−0.7677

−0.49745

−1.03795

Viet Nam

−0.14905

−0.09658

−0.20152

−2.89369

−1.87504

−3.91235

−2.69885

−1.74879

−3.64892

Yemen

−0.16477

−0.10677

−0.22278

−2.95746

−1.91636

−3.99856

−2.88005

−1.86619

−3.8939

Zambia

0.060942

0.039489

0.082395

−3.3312

−2.15853

−4.50386

−3.2075

−2.07838

−4.33663

Zimbabwe

0.279197

0.180912

0.377481

0.862734

0.559029

1.166439

0.811967

0.526133

1.0978
4. Discussion

Over the past 30 years, the global prevalence of pediatric thalassemia has decreased. However, due to increasing medical and social costs, pediatric thalassemia remains a significant public health issue. This study investigated the prevalence, thalassemia-related mortality, and thalassemia-related DALYs among children aged 0 to 14 years in all GBD regions and countries from 1990 to 2021. Our findings provide insights into the burden of pediatric thalassemia in regions and countries with different levels of development over the past 30 years.

From 1990 to 2021, both the number of thalassemia-related deaths and the number of thalassemia-related disability-adjusted life years (DALYs) in children decreased. However, the prevalence increased in low and lower-middle SDI regions, indicating that these areas still face significant challenges in disease control. This may be related to the lack of medical resources, weak public health infrastructure, and insufficient health education in these regions. Additionally, we found a significant negative correlation between SDI and the prevalence, thalassemia-related mortality, and thalassemia-related DALYs. The largest decrease in thalassemia-related mortality in children was observed in high SDI regions, which may be associated with better medical services in these areas, leading to early diagnosis and better treatment of pediatric thalassemia.

Thalassemia is a complex, multifactorial disease influenced by various genetic, metabolic, and environmental factors [10] [11] . The exact role of each factor in pediatric thalassemia is not yet clear and requires further exploration, which may vary by geographic location. These differences in potential factors are related to regional variations in the prevalence and mortality of pediatric thalassemia. Changes in modern dietary patterns have led to a rapid increase in global obesity rates, and obesity is considered a major risk factor for thalassemia and its complications [12] - [14] . Therefore, proactive obesity prevention and dietary management can help slow the progression of pediatric thalassemia.

In children with thalassemia, signs and symptoms are sometimes nonspecific [15] - [17] ; delays in diagnosis can have devastating effects on the child’s health. Children with thalassemia typically initially present with fatigue, weakness, or symptoms of anemia [18] - [20] . Notably, symptoms of anemia are the primary cause of death in thalassemia patients. Therefore, failure to identify high-risk patients and provide timely treatment can lead to adverse outcomes and high mortality rates, especially in low-income countries. This failure may partially explain why pediatric thalassemia-related mortality is lower in higher SDI regions compared to lower SDI regions. Additionally, cardiovascular diseases can also contribute to the mortality of children with thalassemia [21] [22] . For example, chronic anemia can lead to early and progressive atherosclerosis [23] .

Based on the survey results, we propose more specific and actionable policy recommendations, including promoting thalassemia screening programs and public awareness activities in low SDI regions, increasing investment in healthcare resources and improving infrastructure, providing training for healthcare professionals, establishing economic support policies, promoting genetic counseling services, and enhancing international cooperation and aid. These measures aim to improve early detection rates and public awareness of thalassemia, thereby effectively reducing the disease burden in low SDI regions.

 5. Limitations

This study has certain limitations. Although the GBD database provides extensive data, it relies on the reporting and data collection quality of individual countries. Data from some regions may be incomplete or inaccurate, affecting the reliability of the results. Secondly, this study uses a cross-sectional design, which cannot establish causality. While trends can be observed, the specific reasons for these trends cannot be determined.

 6. Conclusions

This study reveals the trends and burden of pediatric thalassemia by analyzing epidemiological data at global, regional, and national levels from 1990 to 2021. Although the prevalence, mortality, and disability-adjusted life years (DALYs) of pediatric thalassemia have decreased globally, significant differences remain between regions and countries with different Socio-demographic Index (SDI) levels.

The burden of pediatric thalassemia has significantly decreased in high SDI regions, indicating substantial progress in disease prevention and control in these areas. However, the prevalence and disease burden have increased in low and lower-middle SDI regions, suggesting that these areas still need to strengthen medical resources, public health infrastructure, and health education.

This study emphasizes the importance of enhancing the understanding of the epidemiology of pediatric thalassemia globally. Future research should further explore the specific needs of low SDI regions and develop effective interventions to reduce the disease burden. Additionally, policymakers and public health workers should focus on regional differences and formulate targeted public health policies and resource allocation strategies to better prevent and control pediatric thalassemia.

In conclusion, this study provides important reference data on the epidemiology of pediatric thalassemia at global, regional, and national levels. These data are crucial for the formulation of public health policies and resource allocation, helping to better prevent and control pediatric thalassemia worldwide.

 Credit Authorship Contribution Statement

Yongle Li: Writing—review & editing, Writing—original draft, Methodology, Formal analysis, Data curation, Conceptualization. Wanshuo Wei, Yuan Gan, Xiaomei Xie, Pengtao Qin, Liangsen Teng: Writing—review & editing, Writing—original draft, Validation, Methodology, Conceptualization. Lihe Jiang: Conceptualization, Funed this research, Writing—review & editing, Writing—original draft, Formal analysis.

 Funding

This study was supported by the Grant of research project on high-level talents of Youjiang Medical College for Nationalities (Grant No. YY2021SK02); Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province (Grant No. 202300011).

 Acknowledgements

We are grateful to the Global Burden of Disease (GBD) Study team for providing access to the comprehensive database used in this analysis.

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