Abstract
Objective
This study used Global Burden of Disease 2021 data to assess the global, regional, and national burden of congenital genitourinary anomalies across 204 countries and territories from 1990 to 2021.
Methods
This cross-sectional study estimated the burden of congenital genitourinary anomalies using prevalence, morbidity, mortality, disability-adjusted life years, and age-standardized rates, including the age-standardized incidence rate, age-standardized death rate, and age-standardization rate. Incidence and prevalence were derived from DisMod-MR 2.1, and a Bayesian age–period–cohort model projected trends until 2035. Analyses were stratified by sex, age, and socio-demographic index.
Results
From 1990 to 2021, the global age-standardized prevalence of female and male congenital genitourinary anomalies increased annually by 0.72% and 0.51%, respectively, with rising disability-adjusted life years across all sociodemographic index regions. Male congenital genitourinary anomalies consistently had higher age-standardized death rates, incidence rates, and age-standardization rates than female cases. By 2021, congenital genitourinary anomalies caused approximately 9700 deaths and affected approximately 5.2 million people, while age-standardized incidence and death rates slightly declined over three decades (age-standardized incidence rate: 18.21 to 17.69 per 100,000; age-standardized death rate: 0.15 to 0.12 per 100,000). Projections to 2035 show continued declines in incidence and death rates.
Conclusions
Despite falling morbidity and mortality, congenital genitourinary anomalies remain a severe global burden. Governments and the public must recognize its gravity and prioritize targeted reproductive health initiatives.
Introduction
Congenital genitourinary anomalies (UCA) are among the most prevalent organ system abnormalities in newborns, defined as “any live birth with urinary or reproductive system disease,” and are often identified prenatally or postnatally with variable severity. 1 Characterized by incontinence, recurrent urinary tract infections, and aberrant genitalia, 2 UCA causes postnatal mortality, increases the risk of end-stage renal disease—particularly for its subset, congenital kidney and urinary tract abnormalities (CAKUT)—and imposes substantial physiological, economic, and psychological burdens on affected individuals and the public.3–6 Despite its significance, global, regional, and national temporal and geographical patterns of UCA burden remain insufficiently characterized.
Global Burden of Disease (GBD) 2021 is an up-to-date dataset on the global burden of urological disease across 204 nations and territories from 1990 to 2021.7–9 Compared with previous GBD studies, this round incorporates new data sources and improves the approaches used to produce current estimates. The purpose of this study was to provide the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of UCA and to examine their changing patterns from 1990 to 2021. We aimed to describe the global, regional, and national burdens and trends of these conditions according to the sociodemographic index (SDI), age, sex, and related risk factors.
No comprehensive analysis of the UCA burden has been conducted using the most recent GBD 2021 data. To address this knowledge gap, our objective was to evaluate the prevalence, morbidity, mortality, and trends in DALYs at the global, regional, and national levels from 1990 to 2021. To identify populations most affected by UCA and to inform targeted prevention and treatment strategies, our analysis was stratified by sex, age, and SDI.
Patients and methods
Data collection
This cross-sectional study adhered to the guidelines of the Declaration of Helsinki (1975, updated 2024), was approved by the Ethics Committee of the First People’s Hospital of Nantong, and waived informed consent for the use of deidentified data. Its approach is consistent with the GBD 2021, which comprehensively evaluated 369 diseases and injuries and 88 risk factors across 204 countries and regions using the most recent epidemiological data and established standardized methods. 10 UCA was defined according to GBD 2021 classification standards, encompassing congenital structural and functional abnormalities of the urinary and reproductive systems, including but not limited to CAKUT, hypospadias, cryptorchidism, renal agenesis or dysplasia, polycystic kidney disease, and double ureters. These conditions were uniformly coded and classified based on the International Classification of Diseases (ICD)-10 and ICD-11 diagnostic criteria to ensure consistency across global datasets. The GBD database employs sophisticated techniques to account for confounding factors and address missing data. The methods and study design of the GBD study have been extensively described in the existing literature. 10 Furthermore, the University of Washington Institutional Review Board waived the requirement for informed consent to access GBD data. 11 This study followed the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) and conformed to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.12,13
Assessment framework
GBD studies utilize advanced modeling techniques to assess the burden of UCA. The DisMod-MR 2.1 tool, which employs Bayesian meta-regression for disease modeling, was used to compute incidence and prevalence. This Bayesian geospatial software combines disease parameters, epidemiological relationships, and geospatial data to generate accurate estimates. 10 The Cause of Death Integrated Modeling (CODEm) framework was utilized for mortality estimation, integrating vital registration and autopsy data, including cases with nonspecific codes. Data were carefully adjusted to ensure accuracy before analysis. 10 CODEm combines multiple models to enhance the precision of mortality estimates and was applied to the 2021 database to produce a comprehensive forecast of the UCA burden. This approach accounts for differences in study design and methodology across data sources to ensure consistent and precise estimates of UCA incidence, morbidity, and mortality.
SDI
The SDI uses data on fertility rates, educational attainment, and per capita income to assess a country’s or region’s level of development. SDI values range from 0 to 1, with higher values indicating higher levels of socioeconomic development.10,14 SDI is recognized as being associated with disease morbidity and mortality. In this study, countries and regions were categorized into five SDI levels—low, low-middle, middle, high-middle, and high—to examine the relationship between UCA burden and socioeconomic development.
Statistical analysis
To standardize variations in population age structure, age-standardized death rates (ASDR), age-standardized incidence rates (ASIR), and age-standardization rates (ASR) were calculated using the GBD standard population distribution to evaluate the impact and patterns of UCA across regions. 15 The Bayesian age–period–cohort (BAPC) framework was selected for trend projection due to its superior performance in handling long-term epidemiological data with age, period, and cohort effects, which are key confounders in UCA burden analysis. According to the literature, the BAPC framework predicts cancer statistics more accurately than alternatives such as generalized additive models, joinpoint regression, and Poisson regression. 16 This study generated predictions of ASIR and ASDR related to UCA from 2021 to 2035 using the BAPC method in conjunction with the nested Laplacian approximation technique.
Results
Global burden and temporal trends in UCA with sex differences
In 2021, UCA caused 9679.14 deaths globally across all age groups (95% uncertainty interval (UI) 6856.52–15,280.21) and affected 5.22 million individuals (95% UI 4.19–6.52 million), with a global incidence rate of 21.88 per 100,000 live births (95% UI 16.64–29.14). From 1990 to 2021, ASIR slightly declined from 18.21 (95% UI 13.85–24.25) to 17.69 per 100,000 (95% UI 13.31–23.25), while ASDR decreased from 0.15 (95% UI 0.11–0.24) to 0.12 per 100,000 (95% UI 0.08–0.19). The DALYs rate also fell from 10.4 (95% UI 7.8–15.7) to 8.8 per 100,000 (95% UI 6.6–12.6) over the same period (Table 1; Supplementary Tables 1 and 2).
Number of cases, rate, and ASR (per 100,000 people) of DALYs for both sexes and for female and male urogenital congenital anomalies in 1990 and 2021.
ASR: age-standardized rate; SDI: sociodemographic index; DALYs: disability-adjusted life years.
Notable sex disparities emerged: although UCA incidence was similar between women and men in 2021, male UCA (MUCA) were associated with significantly higher mortality than female UCA (FUCA). The global DALYs rate was 10.82 per 100,000 (95% UI 7.41–16.49) for FUCA and 16.13 per 100,000 (95% UI 10.97–25.46) for MUCA (Table 1; Supplementary Table 2). Additionally, age-standardized prevalence and DALYs rates increased annually by 0.72% in women and 0.51% in men from 1990 to 2021, with rising burdens across all SDI regions. Men consistently had higher ASDR, ASIR, and age-standardized prevalence rate (ASPR) than women.
Regional, national, and SDI-related disparities
Geographic variations in UCA burden were prominent in 2021 (Figure 1). High-income Eastern Europe (164.25 per 100,000) and Southern Sub-Saharan Africa (127.49 per 100,000) had the highest ASPR among the 21 GBD regions, while Tropical, Southern, and Central Latin America exhibited the highest ASDR. East Asia had the lowest ASDR in 2021 and experienced the second-largest ASDR decline from 1990 to 2021 (estimated annual percentage change (EAPC) = −2.76; 95% UI −2.99 to −2.53) (Supplementary Table 1). Sex patterns in ASPR and ASDR were consistent across regions, with East Asia also recording the lowest ASDR for both FUCA and MUCA (Supplementary Table 2). Regional ASIR trends differed by sex: in Tropical Latin America, FUCA ASIR decreased by 2.63 (95% UI 6.30–11.02), whereas MUCA ASIR increased to 0.95 (95% UI 11.81–21.37) (Supplementary Material 1).
Burden of congenital anomalies of the genitourinary system in 204 countries and regions worldwide. (a) ASIR 2021. (b) ASMR 2021. (c) EAPC for ASIR from 1990 to 2019. (d) EAPC for ASMR from 1990 to 2019. ASIR: age-standardized incidence rate; ASMR: age-standardized mortality rate; EAPC: estimated annual percentage change.
Geographical trends in morbidity and mortality
Morbidity
In 2021, Southern Sub-Saharan Africa had the highest UCA ASIR, while Southeast Asia had the lowest. East Asia experienced the most substantial ASIR increase from 1990 to 2021, whereas Australasia had the smallest change (detailed values in Supplementary Table 1; Figure 1(a) and (c)).
Death
For mortality, North Africa and the Middle East recorded the highest number of UCA deaths in 2021 (1363.11; 95% UI 852.24–2156.77), while Western Europe had the highest age-standardized mortality rate (ASMR) (0.27 per 100,000; 95% UI 0.19–0.36). Oceania experienced the steepest ASMR increase (EAPC = 4.70; 95% confidence interval (CI) 4.45–4.96), whereas High-income Asia Pacific had the most significant decrease (EAPC = −4.29; 95% CI −4.45 to −4.13) (Supplementary Table 1; Figure 1(b) and (d)).
Sex geographic trends
Sex differences in the distribution of ASPR and ASDR for UCA were generally comparable between men and women across GBD regions. In 2021, East Asia exhibited the lowest ASDR for FUCA and MUCA (Supplementary Table 2). Analysis by geographic distribution revealed notable differences in ASIR and their trends between FUCA and MUCA. In Tropical Latin America, ASIR trends diverged by sex, with FUCA decreasing while MUCA increased (Supplementary Material 1).
Factors affecting burden of UCA
In 2021, medium-low SDI regions had the highest mortality and DALYs ASR, followed by low SDI regions, whereas high SDI regions had the lowest burden and experienced a significant decline in ASIR. All SDI regions showed reductions in DALYs and ASMR over the study period, with MUCA consistently exhibiting higher ASIR and ASDR than FUCA across all SDI categories (Table 1; Supplementary Table 1).
We further analyzed the relationship between the initial burden of ASIR and ASDR by EAPC values for 2021 across 204 countries and regions. A slight negative association was observed at the national level between EAPC for ASIR or ASDR and the initial ASIR in 2021, for both male and female cases. Figure 2 illustrates the observed relationships between regional and national ASR and the corresponding SDI for each geographic location in 2021. A significant negative association was found between ASDR (p < 0.0001) or ASR (p < 0.0001) and SDI in DALYs, at both regional and national levels. Between 1990 and 2021, the ASDR and ASR of DALYs exhibited a notable decline across most GBD regions.
Correlations between SDI and ASR at regional and national levels in 2021. (a) ASR of DALYs from 1990 to 2021 in 21 GBD regions. (b) ASDR of congenital anomalies of the genitourinary system. (c) ASR of DALYs. (d) ASDR of UCA in 204 countries and territories in 2021. Expected values based on SDI and disease rates for all locations are shown as black lines. SDI: sociodemographic index; ASR: age-standardized rate; DALYs: disability-adjusted life years; ASDR: age-standardized death rate; UCA: congenital genitourinary anomalies.
Predicting UCA burden of disease
Using the BAPC model, ASPR are projected to increase globally by 2035, from 75.37 to 80.32 per 100,000 in men and from 92.70 to 98.09 per 100,000 in women (Figure 3(a) and (b)). In contrast, ASDR are expected to decrease, from 17.87 to 11.44 per 100,000 in men and 15.78 to 5.93 per 100,000 in women (Figure 3(c) and (d)). ASIR re forecast to decline slightly, from 17.67 to 16.21 per 100,000 in men and 19.80 to 18.33 per 100,000 in women (Figure 3(e) and (f)). ASMR are projected to fall from 0.16 (1990) to 0.11 per 100,000 in men and from 0.14 (1990) to 0.05 per 100,000 in women by 2035 (Figure 3(g) and (h)).
The BAPC model was used to predict overall trends in ASPR (a–b), ASDR (c–d), ASIR (e–f), and ASMR (g–h) for UCA from 2021 to 2035. BAPC: Bayesian age–period–cohort; ASPR: age-standardized prevalence rate; ASDR: age-standardized death rate; ASIR: age-standardized incidence rate; ASMR: age-standardized mortality rate; UCA: congenital genitourinary anomalies.
Discussion
This study comprehensively evaluated the global burden of UCA from 1990 to 2021 and projected trends to 2035 using GBD 2021 data, the latest and most robust dataset for global disease burden analysis. Our findings align with prior research confirming UCA as a prevalent congenital disorder: a Chinese study of 26,989 children reported a 1.67% incidence of CAKUT, 17 while an Italian cohort of 18-year-olds found a 0.96% CAKUT incidence in infants. 18 Globally, CAKUT accounts for 20%–30% of prenatally detected malformations,3,4 supporting our observation that UCA affected over five million people in 2021. However, prior studies were limited to single countries or specific subgroups, such as pediatric populations. In contrast, our analysis covers 204 countries and territories; stratifies by sex, age, and SDI; and provides long-term trends and projections to 2035, offering a more comprehensive global perspective.
A key novel insight is the shifting burden of UCA: while ASIR, ASDR, and DALYs rates have declined globally over the past three decades, ASPR are projected to rise by 2035. This decline in morbidity and mortality is likely driven by advancements in prenatal diagnostics, including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and genetic testing.19,20 These findings indicate a significant shift in the burden of UCA and underscore the necessity of formulating more refined health policies for prenatal diagnosis to reduce morbidity and improve long-term outcomes for affected patients.
Estimates of the burden of UCA differ across regions and countries. The data indicated a decreasing trend in prevalence, morbidity, mortality, and all ASR of DALYs in regions with a high SDI from 1990 to 2021, reflecting the lowest disease burden during this period. Regional UCA disparities, such as high ASPR in high-income Eastern Europe and Southern Sub-Saharan Africa, likely reflect a combination of healthcare access—advanced screening in high-income regions versus limited prenatal care in low-SDI areas—and environmental risk factors, emphasizing the need for context-specific interventions. A plausible explanation is that in high SDI areas, the decline can largely be attributed to aging populations, low birth rates, and advances in technology and public healthcare.21–25 The observed discordance between regions may also be due to variations in malformation inclusion criteria and the characteristics of study populations. Nonetheless, the potential impact of other nonetiologic and etiologic factors, such as genetic and environmental risk factors, remains significant. In 2021, despite all high-income countries in the Asia Pacific region being classified as high-income, their UCA cases exhibited elevated ASPR and ASIR across 204 countries. Consequently, these findings should be interpreted cautiously.6,26 Low-SDI areas bear a disproportionate burden of UCA, manifested by higher mortality rates, increased DALYs, and unmet medical needs. Interventions in these regions must be adapted to local conditions and efficiently utilize resources, including optimizing prenatal care and implementing targeted strategies. For example, UCA screening can involve routine newborn testing.
UCA encompasses various congenital conditions, including polycystic kidney disease and double ureters; however, comprehensive entry data for analysis remain limited. This study uses GBD 2021 data to describe the global characteristics of UCA. Our analysis revealed that men experience a significantly higher burden of UCA compared with women, with mortality, prevalence, and DALYs ratios of approximately 1.5:1 between the sexes. Between 1990 and 2021, the ASIR and ASDR of UCA were consistently higher in men than in women across all SDI categories. Male predominance in UCA burden may stem from biological factors, such as sex-linked genetic regulators of genitourinary development, and potential sex disparities in healthcare utilization, warranting targeted research into male-specific risk factors. Furthermore, sex disparities in UCA burden have exhibited a widening trend, with ASIR and ASDR declining more markedly in women. Numerous studies have reported a notable male predominance in cases of CAKUT.27,28 Research conducted in China indicates a significant prevalence of CAKUT among male newborns,29,30 while findings from Saudi Arabia suggest that approximately 66% of CAKUT cases occur in men. 27 The reasons for this sex difference remain poorly understood. 31 The data sources encompass a broad range of congenital genitourinary disorders, without a specific target condition clearly identified. These limitations complicate discussion and investigation of potential causes for sex differences in UCA. Focusing on a particular disease or a limited subset of UCA is advisable to address this issue, as narrowing the scope allows for more targeted and precise investigations.
This study elucidates the latest epidemiological patterns of UCA burden across age, sex, and SDI categories at global, regional, and national levels. However, the study has inherent limitations. Although we aimed to provide a comprehensive analysis, the accuracy and consistency of data may vary by region, with low-SDI countries often having incomplete surveillance systems and fewer validated datasets, potentially underestimating the true UCA burden or masking subtle trends. Additionally, diagnostic criteria for UCA have evolved over the 31-year study period, including the expanded inclusion of mild anomalies in updated ICD classifications and improved detection through advanced imaging, which may artificially inflate prevalence trends in regions with enhanced diagnostic capacity and complicate direct temporal comparisons. These factors should be considered when interpreting cross-regional and long-term trend findings. Furthermore, our 2035 projections, although based on rigorous statistical models, rely on specific assumptions that may be influenced by external factors. The historical scope of this study, encompassing data from 1990 onward, may also be affected by changes in diagnostic criteria and advancements in medical technology over time. Although our findings provide important insights into global UCA trends, they should be interpreted cautiously, recognizing the nuanced complexities and potential biases inherent in the broader scope of the research.
Conclusion
UCA represent a significant public health issue worldwide, with considerable variation across countries. Although age-standardized prevalence, morbidity, mortality, and DALYs of UCA have decreased over the past 30 years, the burden remains substantial, particularly men in low-income countries. These findings highlight the need for increased awareness among the public and policymakers regarding UCA and its potential risk factors. Targeted preventive and therapeutic interventions for UCA patients may help mitigate the future burden of this disease.
Supplemental Material
sj-pdf-1-imr-10.1177_03000605261426179 - Supplemental material for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study
Supplemental material, sj-pdf-1-imr-10.1177_03000605261426179 for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study by Siyang Xu, Hua Zhu, Cheng Shen, Bing Zheng and Wei Zhang in Journal of International Medical Research
Supplemental Material
sj-pdf-2-imr-10.1177_03000605261426179 - Supplemental material for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study
Supplemental material, sj-pdf-2-imr-10.1177_03000605261426179 for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study by Siyang Xu, Hua Zhu, Cheng Shen, Bing Zheng and Wei Zhang in Journal of International Medical Research
Supplemental Material
sj-pdf-3-imr-10.1177_03000605261426179 - Supplemental material for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study
Supplemental material, sj-pdf-3-imr-10.1177_03000605261426179 for Temporal trends and projections in the global burden of congenital genitourinary anomalies from 1990 to 2021: A cross-sectional study by Siyang Xu, Hua Zhu, Cheng Shen, Bing Zheng and Wei Zhang in Journal of International Medical Research
Footnotes
Acknowledgments
None.
Author contributions
SYX wrote the first draft of the manuscript. Hua Zhu and CS collected and analyzed the data. WZ and BZ supervised the work.
Data availability statement
Data were acquired from the Global Health Data Exchange (https://vizhub.healthdata.org/gbd-results/) and the GBD (
).
Declaration of conflicting interests
The authors declare no competing interests.
Funding
This study was supported by the Clinical Special Research Fund Project of Nantong University (2024LQ019), the Nantong Science and Technology Bureau Project (MSZ2024099), and the Clinical Research Fund Project of Nantong University (2024LY006).
Supplemental material
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References
Supplementary Material
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