1 Introduction
Congenital birth defects mainly refer to abnormal structures or tissues that occur during the development of an embryo [
1]. These defects are usually detected before birth and are pathological conditions characterized by abnormalities or defects in the shape, size, location, or structure of an organ or tissue [
2,
3]. The development of congenital birth defects is usually caused by a complex interaction between genetic factors (such as single gene mutations and chromosomal abnormalities) and environmental factors (such as physical maintenance, exposure to hazardous substances, drug abuse, and infection) [
4–
7]. Most patients with congenital malformations have serious dysfunction and low self-esteem, and need a lot of outside help, which increases the social burden without exception [
8]. Promoting the healthy development of congenital birth defects focuses on early prevention, early diagnosis, and early intervention [
9].
The Global Burden of Disease Study 2021 (GBD 2021) provides comprehensive congenital birth defects data for 204 countries and territories from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates. This makes GBD 2021 a valuable tool for studying congenital birth defects disease burden globally, regionally, and nationally. The socio-demographic indices (SDI) quantify the level of development of a region or country based on data on fertility, education, and per capita income, providing a way to detect health inequalities, analyze absolute and relative inequalities, and reveal the temporal impact of socioeconomic development on the burden of disease [
10]. The World Health Organization (WHO) has proposed a universal health coverage policy with the aim of reducing transnational inequalities and promoting healthy development globally [
11]. The health challenges of congenital birth defects can be met more effectively by in-depth research, policy development, international cooperation, and technological improvement based on the actual situation.
While there are multiple ways to define congenital birth defects, GBD 2021 combines International Classification of Diseases (ICD) codes with the results of disease burden analysis to provide burden estimates for 11 major congenital birth defect types. These congenital birth defects include congenital musculoskeletal and limb deformities (CMLD), congenital heart abnormalities, neural tube defects, Down syndrome, mouth cleft, congenital abnormalities of the digestive tract, and Turner syndrome [
12]. To the best of our knowledge, there has not been a detailed and complete study of the disease burden of CMLD globally, regionally, and nationally. Therefore, it is necessary to analyze and study the epidemiological characteristics of CMLD to inform policy decisions and resource prioritization for adequately addressed CMLD.
We selected the incidence, prevalence, DALYs rates, and mortality data of CMLD in GBD 2021 as the analysis indicators, and the key population for analysis was under-5 children. Based on the latest data from the GBD 2021, we conducted a comprehensive analysis of the incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children from 1990 to 2021 at global, regional and country levels, comparing the distribution and changes in the burden of CMLD in under-5 children by different regions, time periods, genders, and SDI. These analyses and findings provide valuable epidemiological information for research on the prevention and treatment of CMLD, help epidemiologists and health policymakers to develop targeted prevention and treatment strategies, facilitate the efficient allocation of resources, and improve global health outcomes.
2 Methods
2.1 Data sources and important definitions
Data for this study are derived from the GBD 2021 study, which provides information on the global and regional burden of 371 diseases, injuries, and 88 risk factors for 204 countries and territories [
13]. Data are collected through systematic assessments of censuses, household surveys, civil registration and vital statistics, disease registries, disease notifications, use of health services, air pollution monitoring, satellite imaging, and other sources. The breakdown of the ICD codes for CMLD in GBD 2021 is as follows: ICD-10 contains Q65-Q65.2, Q65.8-Q66.1, Q68, Q68.1-Q68.2, Q68.6, Q74, Q74.1-Q74.3, Q74.9-Q75.0, Q75.5, Q75.9-Q76, Q76.1-Q76.49, Q76.8-Q79 and Q79.8-Q79.9, and ICD-9 contains 754-756.19, 756.4-756.59, 756.8-756.9. We extracted disease data for CMLD in under-5 children, including incidence, prevalence, DALYs rates, and mortality. All the data are through the Global Health Data Exchange (GHDx) platform to access and download the data.
The SDI quantify the level of development of a region or country based on data on fertility, education, and per capita income. The value of SDI ranges from 0 to 1, higher SDI values indicate better socioeconomic development. The relationship between SDI level and disease burden was analyzed by calculating the disease rates of countries and territories with different development levels, and the Spearman correlation analysis was used to clarify the relationship between SDI level and disease burden. This classification allows for a more systematic analysis of the impact of socioeconomic development levels on health outcomes.
2.2 Data cleaning and statistical analysis
After obtaining the incidence, prevalence, DALYs rate, and mortality of CMLD in under-5 children from the GBD estimation framework described above, we used Joinpoint regression analysis to identify the years in which incidence, prevalence, DALYs rates, and mortality changed significantly. The number of optimal joinpoints is determined using the Monte Carlo permutation test, allowing a maximum of 4 joinpoints and a minimum of 0 joinpoints. The final model calculates annual percentage change (APC) for the world and for each SDI region to quantify the trend change from 1990 to 2021 and the years of significant change [
14].
In addition, time patterns of CMLD incidence, prevalence, DALYs rates, and mortality under-5 children were quantified using annual percentage change (EAPC). EAPC is an epidemiological indicator for determining the time evolution of corresponding disease rates in epidemiological studies. When the lower bound of the 95% CI value exceeds 0, it indicates an upward trend. When the upper limit of the 95% CI value is below 0, it indicates a downward trend. If the 95% CI contains 0, there is no statistically significant change in the trend pattern.
To conduct a comprehensive analysis and assessment of health inequalities, we compared data from 204 countries and territories between 1990 and 2021 through a cross-country inequality analysis. The cross-country inequality analysis uses the WHO-defined slope index of inequality (SII) and concentration index to measure absolute and relative inequality in disease burden. SII is a measure of absolute inequality that quantifies absolute inequality in health indicators between the most advantaged and least advantaged subgroups of the population using a weighted regression model that considers the overall distribution of socioeconomic factors such as education or wealth. In contrast, the concentration index is a measure of relative inequality quantified by indicating the extent to which health indicators are aggregated in disadvantaged or advantaged groups. A negative SII/concentration index suggests that countries and territories with higher SDI correspond to lower burden of diseases, and vice versa. The greater the absolute value of the SII/concentration index, the greater the inequality [
15].
All analyses and visualizations were performed using the R software (version 4.3.2) and Joinpoint software (version 5.3.0). All analyses were performed using appropriate statistical models, and
P < 0.05 was considered statistically significant [
16].
3 Results
3.1 Global trends
Globally, the number of CMLD incident cases in under-5 children decreased from 2 521 672 cases in 1990 to 2 437 890 cases in 2021. Incidence declined from 406.76 per 100 000 in 1990 to 370.40 per 100 000 in 2021. The overall trend for incidence from 1990 to 2021 showed a significant decline, with an EAPC of −0.20 (95% CI: −0.26 to −0.13) (Table 1, Fig. 1A). However, between 2011 and 2015, the trend for incidence was somewhat upward (APC = 0.36) (Fig. 1A). Globally, the number of CMLD prevalent cases in under-5 children decreased from 4 980 758 cases in 1990 to 4 934 939 cases in 2021. The prevalence declined from 803.43 per 100 000 in 1990 to 749.80 per 100 000 in 2021. The overall trend for prevalence from 1990 to 2021 showed a significant decline, with an EAPC of −0.17 (95% CI: −0.20 to −0.15) (Table S1). However, between 2012 and 2016, the trend for prevalence was somewhat upward (APC = 0.10) (Fig. 1B).
The global number of DALYs in under-5 children due to CMLD decreased from 2 193 955 cases in 1990 to 1 699 811 cases in 2021. The DALYs rates declined from 353.90 per 100 000 in 1990 to 258.26 per 100 000 in 2021. The overall trend for DALYs rates from 1990 to 2021 showed a significant decline, with an EAPC of −0.91 (95% CI: −0.98 to −0.85) (Table S2, Fig. S1). It is worth noting that the decline in DALYs rates was most pronounced between 2016 and 2021 (APC = −2.08) (Fig. S1). Similarly, the number of CMLD deaths in under-5 children decreased from 16 595 cases in 1990 to 11 037 cases in 2021. The mortality declined from 268 per 100 000 in 1990 to 168 per 100 000 in 2021. The overall trend for mortality from 1990 to 2021 showed a significant decline, with an EAPC of −1.35 (95% CI: −1.46 to −1.25) (Table S3, Fig. S2). It is worth noting that the decline in mortality was most pronounced between 2015 and 2021 (APC = −2.88) (Fig. S2). Globally, the incidence, prevalence, DALYs rates, and mortality of CMLD in male children under 5 years of age in 2021 were not significantly different from those in female children (Fig. 2).
3.2 SDI regional level
The incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children decreased in 2021 compared to 1990 in all five SDI regions (Tables 1 and S1–S3). In 2021, the incidence of CMLD in under-5 children was highest in the low SDI region, at 466.44 per 100 000 (95% UI: 323.50 to 652.75), and lowest in the Middle SDI region, at 300.40 per 100 000 (95% UI: 213.77 to 424.45). Similarly, the prevalence of CMLD in under-5 children was lowest in the Middle SDI region at 701.54 per 100 000 (95% UI: 528.41 to 948.10), while the highest was 893.09 per 100 000 in the High-middle SDI region (95% UI: 690.98 to 1173.26). In 2021, the DALYs rates due to CMLD in under-5 children was highest in the low SDI region, at 367.09 per 100 000 (95% UI: 266.75 to 505.52), and lowest in the High SDI region, at 163.41 per 100 000 (95% UI: 120.43 to 221.27). Similarly, mortality of CMLD in under-5 children was highest in the low SDI region and lowest in the High-middle SDI region, at 2.79 per 100 000 (95% UI: 1.89 to 4.16) and 0.55 per 100 000 (95% UI: 0.43 to 0.66) (Tables 1 and S1–S3).
From 1990 to 2021, the incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children at all five SDI regions generally showed a downward trend. The largest decrease in the incidence of CMLD in under-5 children was in the Middle SDI region, with an EAPC of −0.53 (95%CI: −0.62 to −0.43) (Table 1). Similarly, the largest decrease in the prevalence of CMLD in under-5 children was in the Middle SDI region, with an EAPC of −0.35 (95% CI: −0.39 to −0.32) (Table S1). The largest decrease in the DALYs rates of CMLD in under-5 children was in the High-middle SDI region, with an EAPC of −1.64 (95% CI: −1.77 to −1.50) (Table S2). Similarly, the largest decrease in the mortality of CMLD in under-5 children was in the High-middle SDI region, with an EAPC of −3.81 (95% CI: −4.13 to −3.50) (Table S3). From 1990 to 2021, the decreasing trend of incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children showed large fluctuations in the High SDI and High-middle SDI regions (Figs. 1 and S2, Table S1).
3.3 Regional trends
From 1990 to 2021, an improvement in incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children was observed in most of the 21 GBD regions globally (EAPC < 0). However, regions such as the Caribbean, Central Asia, Oceania, and Western Europe showed an increase in incidence (EAPC > 0) (Table 1). The Caribbean, Oceania, and Western Europe have seen an increase in prevalence (EAPC > 0) (Table S1). The High-income North America, and Southern Sub-Saharan Africa have seen an increase in DALYs rates (EAPC > 0) (Table S2). Regions such as High-income North America and Southern Sub-Saharan Africa have seen an increase in mortality ((EAPC > 0) (Table S3).
In 2021, the incidence of CMLD in under-5 children was the highest in the Southern Latin America region at 618.74 per 100 000 (95% UI: 450.95 to 834.50), lowest in the Central Europe region at 226.63 per 100 000 (95% UI: 159.28 to 317.01) (Table 1). The prevalence of CMLD in under-5 children was highest in the High-income Asia Pacific region at 1503.70 per 100 000 (95% UI: 1130.99 to 1968.71), which was lowest in the Central Europe region at 558.15 per 100 000 (95%UI: 425.37 to 740.16) (Table S1). The DALYs rates of CMLD in under-5 children was the highest in Southern Sub-Saharan Africa at 412.01 per 100 000 (95% UI: 274.32 to 547.99), and the mortality of CMLD in under-5 children was highest in Southern Sub-Saharan Africa at 3.60 per 100 000 (95% UI: 2.05 to 5.04) (Tables S2 and S3).
From 1990 to 2021, the regions with the most significant decreases in incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children were High-income Asia Pacific, Central Latin America, North Africa and Middle East, and East Asia, respectively. EAPC was −0.81 (95% CI: −0.92 to −0.71), −0.43 (95% CI: −0.49 to 0.38), −2.58 (95% CI: −2.75 to −2.41), and −6.39 (95% CI: −7.06 to 5.71), respectively (Tables 1 and S1−S3). In 2021, the incidence and prevalence of CMLD in under-5 children was not significantly different from that in female children in almost all GBD regions. Only in a few regions, such as Eastern Sub-Saharan Africa, Southern Sub-Saharan Africa, and Western Sub-Saharan Africa, did male children have higher rates of DALYs and mortality than female children (Fig. 2).
3.4 National trends
As shown in Tables S4–S7, there were significant changes in incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children in each country and territory in 2021 compared to 1990. In 2021, the three countries with the highest incidence of CMLD in under-5 children were Brunei, Guatemala, and Honduras at 732.85 per 100 000, 690.81 per 100 000, and 637.54 per 100 000, respectively. In contrast, the three countries with the lowest incidence of CMLD in under-5 children were the Cook Islands, Northern Mariana Islands, and Puerto Rico, with 170.93 per 100 000, 163.45 per 100 000, and 157.53 per 100 000, respectively (Table S4). The three countries with the steepest declines in the incidence of CMLD among under-5 children between 1990 and 2021 were Equatorial Guinea, Serbia, and South Korea, with EAPC of −1.99, −1.91, and −1.40, respectively. Conversely, the three countries with the most significant increase in the incidence of CMLD in under-5 children were Spain, Georgia, and Ireland, with EAPC scores of 2.45, 1.83, and 1.49 (Table S4). In terms of prevalence, the three countries with the highest prevalence of CMLD in under-5 children in 2021 were Brunei, Japan, and Honduras at 1567.79 per 100 000, 1558.90 per 100 000 and 1508.96 per 100 000, respectively (Table S5). The three countries with the most significant decline in the prevalence of CMLD among under-5 children between 1990 and 2021 were Equatorial Guinea, Maldives, and Qatar, with EAPC of −1.30, −0.911, and −0.86, respectively (Table S5).
The country with the highest levels of both DALYs rates and mortality for CMLD in under-5 children in 2021 was Afghanistan, at 700.30 and 623 per 100 000, respectively (Tables S6 and S7). Notably, over the past three decades, DALYs rates and mortality in CMLD in under-5 children have declined in most countries and territories. Turkey, Iran, and Egypt were the three countries with the largest decline in DALYs rates, with EAPC of −4.48, −3.99, and −3.58, respectively (Table S6). China, Estonia, and the Czech Republic were the three countries with the largest mortality decline, with EAPC of −6.49, −6.42, and −6.01, respectively (Table S7). In contrast, Dominica, Paraguay, and Zimbabwe were the three countries with the most significant increase in the DALYs rates, with EAPC of 2.17, 1.75, and 1.50, respectively. Ecuador, Dominica, and Turkmenistan were the three countries with the most significant mortality increase, with EAPC of 3.33, 2.79, and 2.63, respectively (Tables S6 and S7). Significant differences in incidence, prevalence, DALYs rates, and mortality changes in CMLD in under-5 children were observed across countries and territories (Tables S4–S7).
3.5 The association between burden of CMLD in under-5 children and SDI
SDI is a comprehensive indicator used to assess regional and national levels of development and is intricately linked to the health status of the local population. Our results showed that the incidence, prevalence, DALYs rates, mortality, and EAPC corresponding to the disease rate of CMLD in under-5 children are closely related to SDI level. In 2021, we observed a clear negative association between SDI levels and incidence in 204 countries and territories (R = −0.51, P < 0.001) (Fig. 3A). At the same time, the level of SDI was also negatively correlated with the prevalence rate (R = −0.23, P < 0.001) (Fig. S3). Similarly, a significant negative correlation between SDI levels and both DALYs rates and mortality was observed in 204 countries and territories (R = −0.64, P < 0.001; R = 0.65, P < 0.001) (Figs. S4 and S5). There was no significant positive or negative correlation between EAPC levels and incidence and prevalence (Figs. 3B and S6). Interestingly, we found that EAPC levels were significantly positively associated with both DALYs rates and mortality (R = 0.31, P < 0.001; R = 0.49, P < 0.001) (Figs. S7 and S8). It was worth noting that there was a close relationship between EAPC levels and SDI levels. There was a positive correlation between EAPC of the incidence and prevalence and SDI levels (R = 0.22, P < 0.05; R = 0.15, P < 0.05) (Figs. 3C and S6). There was a significant negative correlation between EAPC of the DALYs rates and mortality and SDI level in (R = −0.26, P < 0.05; R = −0.44, P < 0.05) (Figs. S7 and S8).
3.6 Cross-country inequalities in CMLD at children under-5 years old
As shown in Figs. 4 and 5, we observed clear absolute and corresponding SDI-related inequalities in the disease burden of CMLD in under-5 children, with countries and territories with lower SDI bearing a disproportionate share of the burden. From 1990 to 2021, inequality in incidence for CMLD in under-5 children showed a slight improvement in countries and territories with lower SDI, with SII ranging from −244.30 (95% CI: −288.88 to −199.72) decreased to −222.47 (95% CI: −260.11 to −184.82). However, the concentration index of incidence for CMLD in under-5 children increased from 0.24 (95% CI: −0.36 to −0.11) to −0.29 (95% CI: −0.42 to −0.17), indicating some increase in relative inequality between countries and territories with low SDI (Figs. 4A and 5A). Interestingly, we also observed a decrease in SII in both prevalence and DALYs rates of CMLD in under-5 children, while the concentration index increased. Notably, mortality inequality in CMLD among children under 5 years of age was more stable and smaller in countries and territories with lower SDI, with SII shifting from −2.21 (95% CI: −2.67 to −1.74) in 1990 to −2.03 (95% CI: −2.32 to −1.75) in 2021 (Fig. 4D). However, the concentration index of mortality for CMLD in children under 5 years of age increased from −0.37 (95% CI: −0.46 to −0.27) to −0.46 (95% CI: −0.55 to −0.37) (Fig. 5D). Overall, while absolute inequality in the disease burden of CMLD in under-5 children has improved, relative inequality has worsened.
4 Discussion
Congenital birth defects are a major global public health challenge, placing a significant burden on the lifelong physical and mental health of patients and attracting considerable attention from epidemiologists and health policymakers [
12,
17]. The study innovatively uses GBD 2021 data to assess temporal trends and health inequalities in important populations and congenital birth defects of interest. Our study spans 30 years and includes CMLD data for under-5 children from 5 SDI regions, 21 GBD regions, and 204 countries and territories. This study found that the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021. The disease burden of CMLD in under-5 children varied significantly among different regions and countries, and there was a strong correlation between the corresponding burden of disease and the level of SDI. In addition, we observed clear absolute and corresponding SDI-related inequalities in the disease burden of CMLD in under-5 children, with countries and territories with lower SDI bearing a disproportionate share of the burden.
Globally, CMLD in children has received a lot of attention in the field of congenital malformations, but it has not been adequately addressed in public health and epidemiological studies. Our study shows that while incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children have declined globally from 1990 to 2021, the reduction in the disease burden of CMLD in children under 5 years of age is attributable not only to advances in diagnostic techniques and improved treatment plans but also to critical management of risk factors for CMLD and screening of high-risk individuals, which is consistent with previous studies [
18,
19]. The disease burden of CMLD in under-5 children is increasing significantly in many regions and countries, and this increase is not only due to the high incidence of CMLD, the complexity of the procedure, and the lifelong impact on patients but also due to health inequalities caused by the uneven distribution of medical resources and the lack of health education. In regions and countries with low levels of development, intrauterine infections, nutrition deficiency, exposure to deformation-causing drugs and foods, and lack of opportunities for prenatal diagnosis contribute to the heavy burden of CMLD [
20–
22].
Regionally, the incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children decreased in most of the 21 GBD regions, and the disease burden improved to some extent. However, incidence has increased in regions such as the Caribbean, Central Asia, Oceania, and Western Europe, and prevalence has increased in regions such as the Caribbean, Oceania, and Western Europe. Regions such as the Caribbean, High-income North America, and Southern Sub-Saharan Africa have seen increases in DALYs rates, and regions such as High-income North America and Southern Sub-Saharan Africa have seen an increase in mortality. The incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children varied widely across geographic regions, a pattern consistent with previous evidence [
23,
24]. These differences may also reflect regional differences in healthcare resources, socioeconomic conditions, access to prenatal diagnosis, and awareness. At the national level, compared with 1990, there were significant changes in incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children in each country in 2021. Incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children have decreased significantly in most countries and territories, indicating that the level of medical care and awareness of prenatal diagnosis have improved significantly in most countries and territories. However, the incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children continue to increase in many countries and territories. This highlights the prevalence of uneven distribution of health resources, lack of health education, and low coverage of screening and prevention across borders [
25,
26].
The joinpoint regression analysis showed that the incidence, prevalence, DALYs rates, and mortality of CMLD in under-5 children declined steadily worldwide from 1990 to 2021. However, we observed that the incidence and prevalence of CMLD in under-5 children showed large fluctuations in the High SDI and High-middle SDI regions. Such fluctuations may be related to economic fluctuations in the corresponding regions. The correlation analysis between CMLD disease burden and SDI in under-5 children showed that with the increase of SDI level, the incidence, prevalence, DALYs rates, and mortality of CMLD in children under 5 years of age showed a decreasing trend. It is worth noting that EAPC is positively correlated with SDI level in the incidence and prevalence of CMLD in under-5 children, while EAPC is significantly negatively correlated with SDI level in the DALYs rates and mortality. This is mainly due to the high level of social development in countries and territories with higher SDI, better medical resources, widespread health education, and low coverage of prenatal screening and prevention. The cross-country inequality analysis found clear absolute and relative SDI-related inequalities in the disease burden of CMLD in under-5 children, with countries and territories with lower SDI bearing a disproportionate share of the burden. While absolute inequality in the disease burden of CMLD in under-5 children has improved compared to 1990, relative inequality has worsened. This suggests that advances in healthcare have improved the burden of disease overall, but that these improvements are likely to be concentrated in countries and territories with high levels of development. Because less developed countries and territories have not achieved the same level of improvement due to resource shortages and inadequate health services [
27,
28], there is a need to promote equitable distribution of global health resources, strengthen support for less developed countries and territories, and improve basic health infrastructure and health services.
The profound impact of early congenital malformations on lifelong health is particularly evident in CMLD. These defects of the musculoskeletal system usually manifest early in life and significantly affect an individual’s long-term development and health [
29,
30]. Research has shown that early adverse conditions can lead to the development of CMLD, which can have lasting negative effects on quality of life. Therefore, the long-term burden of CMLD disease and lifelong health can be effectively reduced by strengthening health education, enhancing prenatal care, improving prenatal screening, and increasing early diagnosis and intervention for birth defects. Due to the lack of effective early prevention and intervention, the disease burden of CMLD in under-5 children is more serious in areas with low SDI. Effective early prevention and intervention should be used to effectively reduce the long-term burden of CMLD disease and promote lifelong health. The results of this study further reinforce this idea. In addition to early prevention and intervention, effective treatment and management of CMLD are essential to improve patient outcomes and quality of life [
31]. Early diagnosis, timely surgical intervention, and comprehensive rehabilitation programs are critical to managing these diseases, especially in resource-limited settings. In addition, integration of multidisciplinary care is needed, including psychological support and long-term follow-up [
32], which can significantly improve the quality of life of individuals affected by CMLD. Future public health strategies should not only aim to reduce incidence, DALYs, and mortality but also emphasize long-term care and management of affected individuals to ensure lasting health improvements.
To our knowledge, this study represents the most comprehensive analysis and review to date of the global burden of CMLD in under-5 children, including incidence, prevalence, DALYs, and mortality. However, our study has several limitations that should be taken into account when interpreting the results. First, the quality and availability of data vary widely across regions and countries. Diagnosis and treatment of CMLD in under-5 children in many low-income countries and territories is not timely and correct, which can lead to an underestimation or inaccurate reflection of the true disease burden in these regions. Secondly, CMLD is a broad concept that refers to all congenital malformations of the musculoskeletal system, and categorizing the disease burden as one widespread disease is somewhat challenging. Definitions of CMLD may vary across regions and countries, and some congenital malformations of the musculoskeletal system may not be classified as CMLD in some regions and countries, so estimates of the disease burden of CMLD in under-5 children may be lower than the true burden. Thirdly, the GBD 2021 data are drawn primarily from regional and national reports and publications, which can lead to data integrity, timeliness, and quality issues, especially in low-income areas. Finally, our study relies on the methodological framework of GBD research, however, there may be potential biases in GBD data collection and modeling methods. Despite the limitations of our study, our study provides valuable insights into the global pattern of CMLD burden in under-5 children and provides a basis for future research on the prevention and control of CMLD.
5 Conclusions
Overall, our findings suggest that the global burden of CMLD in under-5 children has improved somewhat, but the burden of CMLD in under-5 children has increased further in some regions and countries. The disease burden of CMLD in under-5 children is significantly different in different socio-economic development regions and countries, especially with lower-income regions and countries bearing a heavier disease burden. In the future, it is necessary to promote equitable distribution of global health resources, strengthen support for countries and territories with low levels of development, and improve basic health infrastructure and medical services.
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