The data for this study were sourced from the GBD 2021 database, which provides comprehensive information on 369 diseases and injuries and 88 risk factors across 204 countries and regions from 1990 to 2021. Specifically, data related to CBDs and their 11 subtypes, including data on the prevalence of, mortality due to, and DALYs attributable to CBDs, were extracted. The data were accessed and downloaded through the Global Health Data Exchange platform (GHDx) (http://ghdx.healthdata.org/gbd-results-tool). The GBD classification system creates a detailed and nonoverlapping catalog of health conditions, which are systematically divided into four levels. In this classification, birth defects are listed under noncommunicable diseases at the first level and further categorized as other noncommunicable diseases at the second level. The birth defects subgroup (B12.1) at the fourth level includes eleven conditions: congenital heart anomalies, congenital musculoskeletal and limb anomalies, digestive congenital anomalies, urogenital congenital anomalies, neural tube defects, Down syndrome, orofacial clefts, Klinefelter syndrome, Turner syndrome, other chromosomal abnormalities and other CBDs. This study utilized a deidentified aggregate dataset, for which individual informed consent was not required. This provision was reviewed and approved by the University of Washington’s ethics review board, which waived the informed consent requirement for this study. As this study utilized publicly available, deidentified aggregate data from secondary sources, no direct involvement of human participants occurred. The study methods comply with the principles of the Declaration of Helsinki. The data sources for the Global Burden of Disease (GBD) database include vital registration, verbal autopsies, censuses, surveys, and disease registries. In the modeling process, GBD handles missing data with Bayesian models and meta-regressions, using data from neighboring regions for estimation. For non-fatal health outcomes, GBD applies microsimulation methods to calculate disability weights and prevalence, generating global health metrics [16].

The purpose of this study was to analyze the trends in the prevalence of, DALYs attributable to, and mortality due to CBDs and their 11 subtypes globally from 1990 to 2021. A range of metrics, including the estimated annual percentage change (EAPC) and average annual percentage change (AAPC), were employed in the analysis. The 95% uncertainty intervals (UIs) were defined by the 2.5th and 97.5th percentiles, representing the 25th and 975th values of 1000 sorted estimates, respectively. These intervals were calculated via the algorithmic methods employed in the GBD study.

To analyze the global distribution and regional differences of CBDs and their subtypes, we generated global maps and conducted regional comparative analyses. The data were aggregated according to the geographic regions defined by the GBD study, and maps were created via the ggplot2 and sf packages in R software (version 4.4.1) to visualize the distribution of disease burden.

All the statistical analyses and data visualizations were conducted via R (version 4.4.1) and the Free Statistical analysis platform (version 1.9, Beijing, China). Descriptive statistics were generated for all key variables, and the results are presented as the means with 95% UIs. For trend analyses, a p value <0.05 was considered to indicate statistical significance.

From 1990 to 2021, the burden of CBDs in children aged 0–14 years, including prevalence, mortality, and DALYs, showed an overall downward trend. While the prevalence across age groups remained relatively stable, the neonatal period (<28 days), as a critical window for identifying and monitoring birth defects, exhibited the highest prevalence, mortality, and DALY rates. The DALY and mortality rates in neonates have significantly decreased over the past three decades (DALYs EAPC: −1.70; 95% UI, −1.75 to −1.64; mortality EAPC: −1.70; 95% UI, −1.75 to −1.65) (Table S4, Figures S1–S2). However, in the trend analysis of prevalence, there was a short-term increase in birth defect prevalence among children aged 0–14 years between 1998 and 2009. Notably, the prevalence of birth defects in infants under 2 years old rebounded in 2015, while other age groups continued to show a steady decline. It is also worth noting that throughout the entire observation period, no significant differences were observed in prevalence, DALYs, or mortality rates based on gender. (Figure 2, Figure S3).

With the advancement of medical technology, the strengthening of public health interventions, and the widespread use of prenatal screening and early diagnosis, the global burden of birth defects has generally shown a declining trend. Analysis of the time trends from 1990 to 2021 indicates that the mortality and DALYs associated with birth defects have decreased overall. However, the prevalence of birth defects experienced a short-term rebound between 1998 and 2009. Although there is currently no literature supporting this data perspective, it may be related to the interaction of multiple factors, including environmental exposure, improvements in diagnostic capabilities, and changes in regional epidemiological characteristics. Specifically, for age groups, the prevalence of birth defects in infants under 2 years old rebounded in 2015, which may be associated with significant advancements in birth defect screening that year, including factors such as regional conflicts, scarcity of medical resources, inadequate public health measures, increased detection rates, the importance of genetic testing, and the development of non-invasive prenatal testing technologies [17–19].

Significant differences were observed in the prevalence and mortality rates of certain CBD subtypes across different geographic regions. The prevalence of, mortality due to, and DALYs attributable to CBDs generally showed a decreasing trend globally, indicating improvements in child health conditions worldwide, particularly in the management and prevention of CBDs. However, there was a slight increase in the prevalence in parts of Central Asia and Oceania, which may be due to multiple factors. First, in some areas of Central Asia and Oceania where mining and industrial activities are concentrated, pregnant women may be exposed to environmental pollution and adverse socioeconomic conditions, thereby increasing the risk of CBDs [20]. Second, genetic factors and changes in population structure, such as an increase in consanguineous marriages, may also lead to an increased incidence of certain hereditary birth defects [21]. Furthermore, with advancements in medical diagnostic technologies, more cases, which may have been previously undiagnosed, are being detected, potentially increasing the prevalence rate [22].

First, in the analysis of CBD subtypes revealed that from 1990 to 2021, congenital musculoskeletal and limb anomalies consistently maintained a high prevalence globally. This may be attributed to the fact that congenital musculoskeletal and limb deformities are often associated with a variety of genetic and environmental factors, such as maternal malnutrition, infections, and exposure to drugs and chemicals, which are prevalent in many regions worldwide, leading to a high incidence of these deformities [23,24]. Previous studies have indicated that malnutrition, diabetes, and exposure to certain environmental toxins are directly linked to the high incidence of musculoskeletal deformities in children [25]. Second, the diagnosis of congenital musculoskeletal and limb anomalies is usually straightforward, and these anomalies are often detected shortly after birth through physical examinations and imaging studies. The high prevalence of heart anomalies as the leading birth defects in regions such as sub-Saharan Africa and certain Asian countries may be related to specific genetic characteristics of certain ethnicities or regions [26]. The prevalence of Turner syndrome is relatively low; this may be because this chromosomal abnormality is usually a random event that primarily affects females, and the occurrence of the condition is not influenced by external environmental factors. The diagnosis of Turner syndrome may require further genetic analysis on the basis of clinical symptoms. One study reported that the global incidence of this syndrome is low, but the rate of diagnosis may be limited by the availability of medical resources and genetic counseling [27]. Despite significant improvements in treatment and management methods worldwide, congenital heart anomalies remain the leading cause of high mortality and DALY rates. This finding is related to the complex structural abnormalities involved in congenital heart anomalies, as well as the extreme diversity in the severity and types of heart anomalies [28]. Even with advances in diagnostic and treatment technologies, some heart anomalies remain difficult to diagnose immediately at birth or are challenging to manage owing to their complex treatment requirements [29]. For example, regions such as sub-Saharan Africa, Central Europe, and Central Asia may lack sufficient medical resources and healthcare facilities, leading to higher mortality and DALY rates for children with heart anomalies in these areas. Moreover, global health inequalities result in significant disparities within the same regions in terms of access to medical resources, medical technology, and healthcare services. These inequalities affect the opportunities for children with heart anomalies to receive early and effective treatment, thereby impacting their risk of mortality and quality of life [30]. While East Asia region may have more abundant medical resources, the area still has high mortality and DALY rates for heart defects due to high population density and genetic factors. From 1990 to 2021, countries such as Georgia (located in the Caucasus region) and Turkmenistan (located in Central Asia) presented increasing prevalence, DALY, and mortality rates for certain specific birth defects, such as congenital heart disease, or other significant subtypes. However, it should be noted that these trends are based on GBD data, and due to the lack of independent studies or recent systematic reviews, there may be biases in the data. Therefore, while the data suggests an increased burden of disease in these countries, the results should be interpreted with caution, considering the influence of factors such as medical facilities, population structure, health behaviors, and environmental and socioeconomic factors [31,32]. Previous studies have shown that socioeconomic status significantly shapes the epidemiological burden of congenital birth defects through its impact on healthcare accessibility, environmental exposures, prevention measures, and long-term management capabilities [33]. Moreover, the analysis in this study further demonstrates a significant correlation between the Social Development Index (SDI) and the burden of congenital birth defects (CBDs). As SDI increases, mortality and disability-adjusted life years (DALY) rates associated with birth defects decrease significantly, which may reflect the improved screening and diagnostic capabilities in higher-SDI regions, leading to the identification of more cases. High-SDI regions typically have better healthcare resources, technological advancements, and public health systems, enabling more effective diagnosis, treatment, and prevention of birth defects, thus reducing the disease burden. In contrast, low-SDI regions often face a heavier burden due to insufficient resources, limited healthcare services, and inadequate health education. These regions have weaker public health infrastructure and limited capacity for early diagnosis and treatment of birth defects, leading to a higher burden of congenital defects. Therefore, to reduce the burden in low-SDI regions, we recommend strengthening public health infrastructure, improving maternal care, and enhancing birth defect prevention efforts. These findings suggest that improvements in socioeconomic development not only reduce the disease burden through better availability and quality of medical resources but also lead to more comprehensive detection and recording of disease burdens, further improving the accuracy of burden assessments.

Although there were no significant differences in the CBD prevalence, mortality, or DALY rates between sexes, the neonatal period (<28 days) represented a critical window for disease burden. This finding highlights the crucial role of early screening and intervention. Early screening for neonatal diseases is prioritized globally because it significantly reduces infant mortality and morbidity by detecting treatable severe conditions early in life. Various policies have been established in different regions to ensure the effective implementation of newborn screening programs (Universal newborn screening: Implementation guidance). For example, in the United States, each state has a mandatory newborn screening program that includes tests for metabolic disorders, endocrine diseases, cystic fibrosis, sickle cell disease, and other serious conditions. While the list of conditions screened may vary by state, there is a recommended uniform screening panel to standardize medical services across all states [34]. The World Health Organization (WHO) also emphasizes the importance of newborn screening in improving maternal and infant care worldwide. The WHO provides guidelines and support to countries that wish to develop or enhance newborn screening programs, highlighting the importance of early detection and intervention. Recent discussions and roundtable meetings have underscored the need to incorporate modern genomic technologies into newborn screening systems and address inequalities in the implementation of newborn screening programs across different regions [35]. These discussions involve a wide range of stakeholders, including patient advocates, healthcare providers, and policy experts, who collaborate to develop feasible policy solutions aimed at enhancing the effectiveness of newborn screening programs. It is recommended that federal and state agencies increase coordination and transparency to streamline the process of adding new conditions to the screening panel. Strengthening improvements and establishing clear guidelines within federal regulation are crucial for maintaining the efficacy of newborn screening systems and for responding to new scientific discoveries and public health needs [34]. Overall, integrating newborn screening into public health policies is crucial for providing early interventions that significantly improve long-term health outcomes for children worldwide. Enhanced support and updated guidelines from international and national agencies can help optimize these programs, leading to the coverage of more conditions and improving diagnostic techniques to ensure that all children, regardless of their place of birth, undergo life-saving screenings. In contrast, the prevalence of birth defects is lowest among children aged 10–14 years, which may be related to natural physiological development and the natural course of diseases during childhood [3].

An in-depth understanding of the characteristics of the global epidemiological distribution and trends of different CBD subtypes provides a scientific basis for future prevention strategies and intervention measures. These results also emphasize the importance of continuous monitoring, international cooperation, and resource optimization in improving global child health. This study has several limitations, mainly related to data sources and data quality. First, while the Global Burden of Disease (GBD) database provides valuable data on a global scale, over-reliance on this database can lead to incomplete or inaccurate data, particularly in low- and middle-income countries (LMICs). These countries often lack comprehensive birth defect registries, and many regions rely on limited hospital records or local data, which can be unrepresentative, potentially underestimating the burden of congenital defects in certain areas. For instance, in resource-limited countries like Myanmar, the lack of data on high-burden diseases such as neural tube defects and congenital heart defects further exacerbates errors in global burden estimates. Additionally, the public health infrastructure in LMICs is generally underdeveloped, with inadequate infrastructure and technology compromising the accuracy and consistency of data, thus affecting the estimation of the birth defect burden. The incidence of birth defects is also influenced by multiple factors, such as the availability of prenatal and neonatal screening, diagnostic capabilities, and biases in sample selection. In regions with limited screening or diagnostic capacity, many birth defects may go undiagnosed or misdiagnosed, leading to an underestimation of the burden. Furthermore, biases in random sample selection may also affect the representativeness of the data, further impacting the accuracy of global burden estimates. Although this study employed data weighting and multi-source calibration methods to mitigate these biases and validated the data by comparing it with data from high-income countries, the impact of missing or low-quality data cannot be fully eliminated. These biases may result in the underestimation of the birth defect burden in LMICs and affect the accuracy of global disease burden estimates. To improve future accuracy, future research should focus on strengthening birth defect screening systems in LMICs, improving diagnostic capabilities, and enhancing data collection and long-term monitoring to reduce data bias and provide a more scientific and accurate basis for the development of public health policies and interventions.