Urogenital congenital anomalies (UGCAs), including congenital anomalies of the kidney and urinary tract and external genital malformations, are major causes of early-life morbidity, preventable mortality, and long-term disability, particularly in low-resource settings. This study assessed the global burden, temporal trends, regional disparities, and future projections of UGCAs in children under 9 years using the Global Burden of Disease (GBD) 2021 dataset.
MethodsGBD 2021 data were used to estimate incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in children aged 0–8 years. Analyses were stratified by sex, age, Socio-demographic Index (SDI), region, and country. Age-standardized rates (ASRs), SDI associations, and decomposition analyses were conducted, and future trends were projected using ARIMA and Holt–Winters models. Estimates are presented with 95% uncertainty intervals (UIs).
ResultsFrom 1990 to 2021, global age-standardized incidence (ASIR) and prevalence rates (ASPR) remained stable, whereas mortality and DALY rates declined. In 2021, incidence was 2026,032 (95% UI: 1417,198–2787,372), prevalence 3360,751 (2594,010–4411,084), DALYs 5122,959 (4069,356–6172,763), and deaths 58,906 (46,861–70,940). ASRs were 150.46 per 100,000 for incidence, 248.91 for prevalence, 384.10 for DALYs, and 4.41 for deaths. Females had higher ASIRs and ASPRs, while males showed higher mortality and DALY rates. Incidence and prevalence increased with age, whereas mortality declined. With increasing SDI, incidence and prevalence rose, while mortality decreased. The burden is increasingly concentrated in low-SDI regions; Southern Sub-Saharan Africa was the only region with rising mortality. CAKUT remained the predominant subtype globally. Projections indicate continued declines in mortality, with stable incidence and prevalence.
ConclusionAlthough global mortality and DALYs from UGCAs have declined, the growing burden in low-SDI regions highlights persistent inequalities and the need for targeted interventions.
Urogenital congenital anomalies (UGCAs), including congenital anomalies of the kidney and urinary tract (CAKUT) and malformations of the external genitalia, are major contributors to neonatal and early-childhood morbidity and mortality worldwide, second only to preventable perinatal conditions in many settings [1]. Global estimates indicate that hundreds of thousands of children are affected annually, with many experiencing long-term renal and reproductive complications if not diagnosed and treated in a timely manner [2,3]. Despite their clinical significance, UGCAs remain under-recognized, particularly in low- and middle-income countries where birth-defect surveillance systems are limited [4,5]. Compared with advances in adult urology and nephrology, progress in pediatric UGCA management has been uneven. Care often depends on limited surgical and supportive interventions, with restricted access to prenatal screening, neonatal surgery, interventional nephrology, and long-term multidisciplinary follow-up. As a result, many affected children develop chronic complications, including chronic kidney disease, hypertension, recurrent urinary tract infections, subfertility or infertility, and psychosocial challenges [6,7]. The burden also extends to families, who frequently experience psychological stress and financial strain related to prolonged care needs.
In addition, marked geographic disparities persist in outcomes. Mortality and disability attributable to congenital anomalies remain disproportionately high in low-resource settings, whereas high-income regions benefit from early detection, timely referral, and standardized care pathways [8,9]. These inequalities highlight ongoing gaps in prevention and treatment and suggest uneven progress toward global targets for reducing preventable deaths and disability from birth defects by 2030. Although studies using the Global Burden of Disease (GBD) framework have expanded, most have focused on specific anomalies or regions rather than the full spectrum of UGCAs [10,11]. Importantly, most cases are identified in early childhood, with the majority diagnosed before 9 years of age. In this study, the authors used data from GBD 2021 to provide a comprehensive assessment of the global burden of UGCAs in children under 9 years. The authors evaluated temporal trends, regional disparities, and future projections to inform prevention strategies, optimize resource allocation, and support improvements in child health.
MethodsData sources and study designThe authors used data from the Global Burden of Disease (GBD) 2021 study to assess the burden of UGCAs among children aged 0–9 years at global, regional, and national levels from 1990 to 2021, with projections to 2036. Data were obtained from the Global Health Data Exchange (GHDx), which compiles standardized estimates for 371 diseases across 204 countries and territories [12]. UGCAs were defined according to GBD cause classifications and corresponding ICD codes (ICD-10: Q50–Q56, Q60–Q64; ICD-9: 752.x, 753.x). Estimates were derived from multiple sources, including vital registration, hospital records, registries, and surveys, with adjustments for underreporting and misclassification.
The authors extracted incidence, prevalence, mortality, and disability-adjusted life years (DALYs), where DALYs comprise years of life lost (YLLs) and years lived with disability (YLDs). Socioeconomic development was measured using the Socio-demographic Index (SDI), a composite indicator of income, education, and fertility, categorized into five quintiles. This study followed GATHER guidelines; ethical approval was not required as all data were de-identified and publicly available.
Burden estimation and stratificationThe authors calculated age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and DALY rates (ASDR), each with 95% uncertainty intervals (UIs), across countries, 21 GBD regions, and SDI quintiles. Analyses were stratified by sex and age groups (< 1, 1–4, and 5–9 years). For age-specific aggregation, estimates were derived by weighting each age group according to its population proportion rather than by simple summation. Specifically, for a given metric, the combined estimate was calculated as:
where ri denotes the age-specific rate for group i and wi represents the corresponding population weight. Absolute counts (incidence, prevalence, deaths, and DALYs) were also summarized, with DALYs further decomposed into years of life lost (YLLs) and years lived with disability (YLDs). Geographic patterns and temporal trends were visualized using standardized mapping approaches.SDI correlation analysis
Associations between SDI and UGCA burden indicators (counts and age-standardized rates) were assessed using Pearson correlation at global and national levels, with Spearman correlation used in sensitivity analyses to account for nonlinearity and outliers [13].
Decomposition analysisChanges in absolute burden from 1990 to 2021 were decomposed into three components: population growth, age structure shifts, and epidemiological changes (age-specific rates) [14]. A stepwise replacement (Das Gupta) method was applied, consistent with GBD practice. Uncertainty was propagated using 1000 posterior draws, and results are presented as medians with 95% UIs. Sensitivity analyses assessed robustness to component ordering.
Health inequality analysisInequalities in ASMR and ASDR were quantified using the Slope Index of Inequality (SII) and Concentration Index (CI) [15]. SII was estimated via population-weighted regression across SDI ranks, representing absolute differences, while CI captured relative inequality (range −1 to +1). Analyses were conducted globally, by region, and by country for 1990 and 2021, with 95% confidence intervals obtained via bootstrap resampling.
Forecasting analysisFuture trends were projected using AutoRegressive Integrated Moving Average (ARIMA) models, with Holt–Winters exponential smoothing applied as a complementary approach to assess robustness [16,17]. Both methods were selected due to their suitability for epidemiological time-series data without requiring strong parametric assumptions. Models were fitted to annual time series (1990–2021) for incidence, prevalence, mortality, and DALYs at global, regional, SDI, and national levels, where data were sufficiently complete. For ARIMA models, orders (p, d, q) were determined using a combination of autocorrelation function (ACF), partial autocorrelation function (PACF), and minimization of Akaike and Bayesian Information Criteria (AIC/BIC). Holt–Winters models were specified with additive or multiplicative components based on data structure and seasonal diagnostics. Model adequacy was evaluated using residual diagnostics, including Ljung–Box tests for independence and assessment of stationarity and residual distribution. Forecasts are presented with 95% prediction intervals.
Statistical softwareAll analyses were conducted using R (version 4.3.3) and Stata 18. Mapping and visualization were performed using ArcGIS, QGIS, and R packages. Statistical significance was defined as p < 0.05. GBD estimates are presented with 95% UIs, and forecasts with 95% prediction intervals.
ResultsGlobal burden of UGCAs in children under 9 years (1990–2021)From 1990 to 2021, global incidence and prevalence of UGCAs remained relatively stable, with minor fluctuations. In 2021, there were 2026,032 incident cases (95% UI: 1417,198–2787,372) and 3360,751 prevalent cases (95% UI: 2594,010–4411,084), corresponding to ASIR and ASPR of 150.46 and 248.91 per 100,000, respectively. Compared with 1990, incidence and prevalence increased slightly by 0.99% and 4.49%, with EAPCs of −0.31 and −0.06. In contrast, mortality and DALYs declined markedly. In 2021, DALYs totaled 5122,959 (95% UI: 4069,356–6172,763) and deaths 58,906 (95% UI: 46,861–70,940), with ASDR and ASMR of 384.10 and 4.41 per 100,000, respectively. Relative to 1990, DALYs and deaths decreased by 45.28% and 45.32%, with EAPCs of −2.16 and −2.18 (Figure 1 and Tables 1, 2, 3 and 4).
The incidence cases and age-standardized incidence rate of Urogenital Congenital Anomalies in Children Under 9 Years in 1990 and 2021, along with their temporal trend.
EAPC, estimated annual percentage change; SDl, Sociodemographic Index; Ul, uncertainty interval. EAPC is expressed as 95% CIs.
The prevalence cases and age-standardized prevalence rate of Urogenital Congenital Anomalies in Children Under 9 Years in 1990 and 2021, along with their temporal trend.
EAPC, estimated annual percentage change; SDl, Sociodemographic Index; Ul, uncertainty interval. EAPC is expressed as 95% CIs.
The Deaths cases and age-standardized Deaths rate of Urogenital Congenital Anomalies in Children Under 9 Years in 1990 and 2021, along with their temporal trend.
EAPC, estimated annual percentage change; SDl, Sociodemographic Index; Ul, uncertainty interval. EAPC is expressed as 95% CIs.
The DALYs cases and age-standardized DALYs rate of Urogenital Congenital Anomalies in Children Under 9 Years in 1990 and 2021, along with their temporal trend.
EAPC, estimated annual percentage change; SDl, Sociodemographic Index; Ul, uncertainty interval. EAPC is expressed as 95% CIs.
Trends were broadly consistent across sexes, although incidence and prevalence were higher in females, while deaths and DALYs were higher in males. In 2021, male-to-female ratios were 0.69:1 for incidence, 0.82:1 for prevalence, 1.41:1 for deaths, and 1.40:1 for DALYs; corresponding ASR ratios were 0.64:1, 0.77:1, 1.32:1, and 1.31:1. Across age groups, incidence, prevalence, deaths, and DALYs increased with age, whereas ASMR and ASDR declined, particularly in younger children. Compared with 1990, ASRs, deaths, and DALYs declined across all age groups, while total case numbers remained stable; morbidity increased in children aged 5–9 years (Figure 2).
By SDI, deaths, DALYs, and their ASRs decreased with increasing SDI, whereas ASIR and ASPR increased. Middle-SDI regions had the highest morbidity and prevalence, while high-middle and middle SDI regions experienced the greatest reductions in deaths and DALYs (Figure 3 and Tables 1, 2, 3 and 4).
Comparison of the disease burden of urogenital congenital anomalies (UGCAs) for children under 9 years old in 1990 and 2021 across different SDI and GBD regions (A. Different SDI regions; B. Absolute numbers across different GBD regions; C. Age-Standardized Rates (ASRs) across different GBD regions).
At the regional level, Southern Sub-Saharan Africa was the only region with increasing ASMR and ASDR. Declines were most pronounced in East Asia, Eastern and Central Europe, and high-income regions. Approximately one-third of regions showed increasing ASIRs and two-thirds increasing ASPRs, with overlapping trends in South Asia, High-income North America, Andean Latin America, and Southern Sub-Saharan Africa. In 2021, the highest ASIRs and ASPRs were observed in high-SDI regions (e.g., Central and Eastern Europe, High-income Asia Pacific, North America), whereas the highest ASMRs and ASDRs occurred in low-SDI regions (e.g., Eastern and Western Sub-Saharan Africa, Caribbean, Andean Latin America). Differences reached up to 14-fold for incidence and 10-fold for prevalence, and approximately fivefold for mortality rates. South Asia contributed the largest absolute burden, accounting for 31.36% of incident cases and ∼22% of deaths and DALYs.
Country-level patterns were heterogeneous. High ASIRs and ASPRs were observed in parts of Europe, Central Asia, and several African countries. The highest mortality rates were concentrated in low-SDI countries, while the lowest occurred in high-SDI settings, with differences up to 18-fold. Rapid increases in ASIRs were observed in countries such as India, the United States, and Poland, whereas mortality increased in selected countries, including Zimbabwe and Botswana. Absolute burdens were highest in populous countries such as China and India (Figure 4 and Supplement Tables 1–4).
SDI correlation analysis
UGCA burden showed consistent associations with SDI. Incidence and prevalence were positively correlated with SDI (regional ρ = 0.28 and 0.43; national ρ = 0.60 and 0.66; all p < 0.001), whereas deaths and DALYs were negatively correlated (regional ρ = −0.48 and −0.47; national ρ = −0.67 and −0.66; all p < 0.001) (Figure 5).
Health inequities
Inequality analyses revealed persistent and widening disparities in the burden of UGCAs. Incidence and prevalence were increasingly concentrated in high-SDI regions, with concentration indices rising from 0.18 to 0.21 and from 0.16 to 0.20, respectively. In contrast, deaths and DALYs became more concentrated in low-SDI regions, with concentration indices declining from −0.03 to −0.16 and from −0.03 to −0.15 (Figure 6). These opposing gradients are consistent with SDI correlation analyses, which showed positive associations between SDI and incidence/prevalence but negative associations with mortality and DALYs. They are also aligned with decomposition findings, indicating that population growth and improved detection contribute to higher case identification in higher-SDI settings, whereas slower epidemiological improvements in low-SDI regions limit reductions in fatal and disability outcomes.
Decomposition analysis
Population growth was the main contributor to increased incidence and prevalence in low and low-middle-SDI regions (e.g., Western Sub-Saharan Africa, South Asia), but contributed negatively in higher-SDI regions. Epidemiological changes were the primary drivers of declining deaths and DALYs globally, particularly in middle and high-middle SDI regions, although their beneficial impact was weaker in low-SDI regions and reversed in South Asia. Ageing had minimal overall impact (Figure 7).
2035 Predictions
Both ARIMA and Holt–Winters models projected continued declines in UGCA-related deaths and DALYs over the forecast period. However, the two approaches yielded divergent patterns for incidence and prevalence. Specifically, ARIMA models suggested a potential increase in incidence after 2030, followed by a corresponding rise in prevalence, whereas Holt–Winters models indicated relatively stable trends. These discrepancies likely arise from differences in model structure and sensitivity to long-term trends and recent fluctuations. Accordingly, these projections should be interpreted with caution, as they reflect methodological variability rather than consistent evidence of future increases. Overall, the results highlight uncertainty in forecasting morbidity trends, while the declining trajectory of mortality appears more consistent across models (Figure 8).
Discussion
This study provides a comprehensive synthesis of the global burden of UGCAs in children under 9 years, outlining current patterns, long-term trends since 1990, and key drivers. Three main findings emerge. First, while incidence and prevalence have remained stable or slightly increased, age-standardized mortality and disability-adjusted life years (DALYs) have declined across most regions. This divergence likely reflects population growth and improved detection alongside advances in antenatal screening, neonatal surgery, pediatric nephrology, and infection control [6,18]. Second, the burden varies markedly by sex, age, geography, and sociodemographic development, with mortality and disability disproportionately concentrated in low-SDI settings. Third, both modifiable maternal factors (e.g., pregestational diabetes, teratogenic exposure, and obesity) and health system capacity (e.g., antenatal ultrasound, surgical and nephrology services, access to dialysis/transplantation, and long-term follow-up) represent critical intervention targets [19].
The coexistence of increasing incidence/prevalence and declining mortality/DALYs suggests that expanded detection and demographic growth are enlarging the identified case pool, while improvements in care are reducing fatality and disability. Increased use of antenatal ultrasound and structured postnatal evaluation has enhanced detection of milder anomalies, particularly in high-resource settings [20,21]. Consistently, decomposition analyses indicate that population growth is the primary driver of rising case numbers, whereas reductions in age-specific fatality account for declines in deaths and DALYs, in line with Global Burden of Disease findings [3].
Age and sex gradients further clarify underlying mechanisms. Mortality is concentrated in the neonatal and early-infant period, when severe obstructive uropathies and bilateral renal dysplasia present with respiratory compromise, electrolyte imbalance, and sepsis risk [22]. Among survivors, the accumulation of nonfatal sequelae—such as recurrent urinary tract infections, renal scarring, hypertension, and growth impairment — drives increasing prevalence with age [6]. Sex differences are both biological and clinical: male-specific posterior urethral valves disproportionately increase deaths and years of life lost, whereas higher detection of vesicoureteral reflux and UTIs in girls elevates morbidity. Consequently, deaths and DALYs tend to be higher in boys, while incidence and prevalence may appear higher in girls in settings with more complete detection.
A pronounced sociodemographic gradient is evident. Higher age-standardized incidence and prevalence in high-SDI regions likely reflect more comprehensive detection and structured screening, whereas deaths and DALYs remain concentrated in low- and middle-SDI settings due to constrained access to surgery, nephrology care, and renal replacement therapies [23]. This divergence underscores persistent inequities; accordingly, outcome-based indicators—such as CKD progression, UTI-related hospitalization, and UGCA-attributable mortality—may better capture health system performance than prevalence alone [24,25].
These inequalities are closely linked to both health system capacity and demographic dynamics. In high-SDI regions, higher incidence and prevalence largely reflect more complete case ascertainment, particularly for milder conditions. In contrast, excess mortality and DALYs in low-SDI settings are driven by delayed diagnosis, limited pediatric surgical and nephrology services, and fragmented follow-up care [26] Decomposition analyses further support this interpretation, showing that although population growth increases case numbers globally, reductions in deaths and DALYs are primarily driven by epidemiological improvements that are unevenly distributed and substantially weaker in low-SDI regions. Together, these findings indicate that observed disparities arise less from differences in disease occurrence than from inequities in detection, treatment access, and health system performance. Addressing these gaps will require targeted investments in prenatal screening, pediatric surgical capacity, and long-term nephrology care in resource-limited settings.
Although no single high-impact strategy exists, several maternal exposures are consistently linked to UGCA risk, including pregestational diabetes, poor glycemic control, teratogenic medications (e.g., ACE inhibitors/ARBs), and obesity. Assisted reproductive technologies and advanced maternal age may further elevate risk, reinforcing the importance of preconception counseling and early medication review. Integrating these measures into primary and antenatal care — glycemic optimization, teratogen avoidance, and weight management — offers a scalable prevention approach across diverse settings.
Advances in genetics are refining risk stratification and clinical management. Monogenic variants (e.g., HNF1B, PAX2, EYA1, SALL1) and copy-number alterations explain a subset of cases, often accompanied by extra-renal manifestations. Targeted genetic testing can improve diagnostic precision and inform counseling; however, limited access in low-resource settings risks exacerbating existing disparities. Clinical progress has shifted UGCAs from high fatality toward chronic morbidity. Antenatal ultrasound and standardized postnatal pathways facilitate early detection and timely intervention, while advances in pediatric urology and nephrology reduce complications and help preserve renal function. Nevertheless, a substantial proportion of patients progress to chronic kidney disease, necessitating long-term follow-up and structured transition to adult care. Psychosocial and economic burdens remain considerable, underscoring the need for integrated support systems. This GBD-based analysis enables standardized cross-country comparisons over time but has important limitations. Reliance on ICD-based classification restricts phenotypic granularity, under-ascertainment in low-resource settings may introduce bias, and DALYs do not capture detailed clinical outcomes or service capacity.
ConclusionUGCAs serve as a sensitive indicator of pediatric health system performance and equity. Priority actions include strengthening maternal risk control and ensuring equitable access to antenatal screening, specialized care, genetic services, and long-term management to reduce CKD progression and improve outcomes.
Ethics declarationEthical approval was not required for this secondary analysis of publicly available, aggregated estimates from the Global Burden of Disease (GBD) study, as no individual-level data were used.
Authors’ contributionsConceptualization: Sheng Gong; Methodology: Sheng Gong, Jianming Zhu,; Software and Data Curation: Sheng Gong; Formal Analysis and Visualization: Guoping Jiang, Weiwei Ruan; Validation: Guoping Jiang, Weiwei Ruan; Investigation: Guoping Jiang, Weiwei Ruan; Writing – Original Draft: Sheng Gong, Jianming Zhu; Writing – Review & Editing: Sheng Gong; Supervision: Sheng Gong; Project Administration: Sheng Gong; Funding Acquisition: Sheng Gong, Jianming Zhu. All authors have read and agreed to the published version of the manuscript.
FundingMedical and Health Research Project of Zhejiang Province (General Project) (2025KY1417), Ningbo Medical Key Discipline (2026-A36). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all study data and had final responsibility for the decision to submit for publication.
Data availability statementThe datasets generated and/or analyzed during the current study are derived from the Global Burden of Disease Study 2021 (GBD 2021), which is publicly available through the Institute for Health Metrics and Evaluation (IHME) GBD Results Tool at https://vizhub.healthdata.org/gbd-results/. The exact datasets used in this analysis can be replicated by applying the same selection criteria (e.g., location, year, metric, cause) as detailed in the Methods section. All data generated from the secondary analysis (e.g., calculated rates, trend analyses) are available within the article and its supplementary information files.
The authors declare no conflicts of interest.
