Global, regional and national burden of pancreatitis in children and adolescents, 1990-2021: a systematic analysis for the global burden of disease study 2021.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas with a rising global incidence across all age groups, including children and adolescents [ 1 ]. Once considered rare in paediatric populations, AP, along with chronic pancreatitis (CP), has become increasingly recognized in recent decades, with evidence suggesting a decrease in the age of onset and an increase in hospitalizations [ 2 , 3 ]. In the United States, paediatric pancreatitis incidence has risen significantly over the past 15 years, correlating with shifts in epidemiological risk factors and improved diagnostic awareness [ 4 ]. Unlike adult pancreatitis, paediatric AP is characterized by distinct etiological factors, clinical presentations and prognostic outcomes, often leading to more severe complications and long-term morbidity [ 5 ]. The primary causes of AP vary across age groups. In children under 5 years, genetic factors (e.g. CFTR, PRSS1 and SPINK1 mutations), infections and trauma are the leading contributors [ 6 ]. As children grow older, environmental and lifestyle factors, such as obesity and gallstone disease, become more prominent [ 7 ]. Among adolescents, alcohol and substance use are increasingly significant risk factors, particularly in the 15–19 years age group [ 8 ]. These age-specific variations underscore the importance of understanding the distinct etiologies of paediatric pancreatitis to guide prevention and management efforts. Despite recognizing these risk factors, comprehensive epidemiological assessments of paediatric pancreatitis remain scarce. Most research focuses on adults, with limited data on disease burden, mortality and disability-adjusted life years (DALYs) in children and adolescents. With children and adolescents representing 16% of the global population, particularly in low- and middle-income countries [ 9 ], paediatric health issues are increasingly vital for public health policy. This study utilizes the global burden of disease (GBD) 2021 dataset to systematically assess the global, regional and national burden of pancreatitis in those under 20, with stratifications by age, sex and socio-demographic index (SDI). Additionally, projections of AP-related mortality through 2035 offer valuable insights into future disease burden, informing targeted public health interventions.

This study has been registered on the GBD 2021 proposal form ( https://uwhealthmetrics.co1.qualtrics.com/ ). For this study, death and DALYs estimates, along with their 95% uncertainty intervals (UIs), for pancreatitis in individuals under 20 were sourced from the GBD 2021 database ( http://ghdx.healthdata.org/gbd–results–tool ) [ 10 ]. The GBD 2021 framework employs a Bayesian meta-regression approach to synthesize epidemiological data while adjusting for known biases. The UIs capture uncertainty from multiple sources, including data sparsity, sampling error and model assumptions, and are derived from 1000 posterior draws, with the 2.5th and 97.5th percentiles defining the 95% UI. The GBD 2021 database utilizes the latest epidemiological data and enhanced standardization methods, offering a comprehensive assessment of 369 diseases and injuries, encompassing 87 associated risk factors [ 11 ]. It encompasses 21 GBD regions and 204 countries/territories globally. Cases of pancreatitis were identified based on the diagnostic criteria from the International Classification of Diseases, Tenth Edition (ICD-10)/Ninth Revision (ICD-9) [ 10 ] ( Table S1 ). Given the use of publicly accessible, de-identified datasets, ethical review or approval from institutional review boards was not required. The SDI, developed by GBD researchers, is a composite indicator of societal development, closely associated with health outcomes. It ranges from 0, representing the minimum development for health outcomes, to 1, indicating the maximum development [ 12 ], with regions and countries categorized into five tiers: low, low-middle, middle, high-middle and high. This study sought to characterize the burden of pancreatitis among children and adolescents by assessing death and DALYs across genders and age groups globally, regionally and nationally. Additionally, the Bayesian age–period–cohort (BAPC) model was employed to project future disease burdens, forecasting deaths and age-standardized death rate (ASDR) for pancreatitis in children and adolescents from 2022 to 2035. The BAPC and INLA packages within R software (v4.4.0) (R Foundation for Statistical Computing, Vienna, Austria) were used for these projections. A Poisson linear model was used to estimate the annual percentage change (EAPC) in trends over specific intervals. An EAPC and its 95%CI greater than 0 suggest an increasing trend; less than 0, a decreasing trend; and around 0, a stable trend over the period. All analyses and visualizations were performed using R software (v4.4.0) (R Foundation for Statistical Computing, Vienna, Austria).

In 2021, pancreatitis resulted in 1120.09 deaths among children and adolescents (95% UI, 919.289–1394.85), accounting for 2% of all pancreatitis-related fatalities. From 1990 to 2021, the ASDR for pancreatitis exhibited a steady annual decrease, with an EAPC of −0.92 (95%CI, −1.15, −0.69). In 2021, global DALYs attributed to pancreatitis in this age group totalled 100041.07 person-years (95% UI, 81771.41–120957.63). Similarly, the age-standardized DALY rate showed a decline, with an EAPC of −0.86 (95%CI, −1.05, −0.67). Among the five SDI regions, the low-middle SDI region exhibited the highest ASDR and age-standardized DALYs rate for pancreatitis. Encouragingly, a significant reduction in pancreatitis burden was observed across all SDI regions ( Figure 1(A,B) ). Notably, Andean Latin America, Central Latin America and Eastern Europe had the highest ASDR and age-standardized DALYs rate. Eastern Sub-Saharan Africa experienced the most significant increase, whereas the high-income Asia Pacific and East Asia regions saw the most considerable decrease. Notably, Georgia reported the highest number of deaths, and Guyana had the highest DALYs due to pancreatitis ( Figure 2(A,B) ). Tonga, North Macedonia and Guinea had the highest ASDR, while Tokelau, Niue and Guatemala had the highest age-standardized DALYs rate ( Table S2 ). The EAPC of ASR burden for pancreatitis in children and adolescents, 1990–2021: a global, SDI and 21 GBD regions analysis by sex. Panel A shows the EAPC of the ASDR for pancreatitis, and panel B focuses on the EAPC of the age-standardized DALYs rate in pancreatitis. In the bar charts, red bars represent the combined male–female data, offering an overall view of the pancreatitis burden. Blue bars are dedicated to female-specific data, and orange bars denote male-specific data. EAPC: estimated annual percentage change; ASR: age-standardized rate; GBD: global burden of diseases, injuries, and risk factors study; SDI: socio-demographic index; DALY: disability-adjusted life year; ASDR: age-standardized death rate. The EAPC of the ASR burden of pancreatitis in children and adolescents across 204 countries and territories, 1990–2021. Panel A shows the EAPC of the ASDR for pancreatitis, and panel B focuses on the EAPC of the age-standardized DALYs rate in pancreatitis. The colour-coding on the world maps in each panel corresponds to different ranges of EAPC values, as indicated by the legends at the bottom-left of each map. EAPC: estimated annual percentage change; ASR: age-standardized rate; DALY: disability-adjusted life year; ASDR: age-standardized death rate. Globally, pancreatitis-related death and DALYs in children and adolescents declined across all age groups, with the under-5 age group showing the most significant reduction ( Figure S1 ). The 15–19 age group exhibited the highest ASDR and age-standardized DALYs rate for pancreatitis. From 1990 to 2021, both ASDR and age-standardized DALYs rate for pancreatitis showed a downward trend, with a more pronounced decline in ASDR, especially among the youngest ( Figure S2A,B ). In 2021, adolescents aged 15–19 in all regions experienced the highest number of deaths and DALYs due to pancreatitis. Notably, Southern Sub-Saharan Africa’s burden increase had a distinct age composition, with the 15–19 age group playing a pivotal role ( Figure S3A,B ). Gender differences in pancreatitis burden among children and adolescents were evident ( Figure 3 ). In 2021, females comprised 37.18% (416.44 cases) and males 62.82% (703.65 cases) of global pancreatitis-related deaths in children and adolescents. Females accounted for 39.01% and males 60.99% of DALYs ( Table 1 ). Males generally had higher ASDR and DALYs rate than females across all age groups, except for a slightly higher ASDR in females aged 10–14 ( Figure 3(A,B) ). Except for Andean Latin America, Australasia and Oceania, males had higher pancreatitis death and DALYs rate than females in all other regions ( Tables S3 and S4 ). Death and DALYs rate of pancreatitis in children and adolescents in 2021 across global, SDI and 21 GBD regions, by age group and sex. Panel A shows the ASDR for pancreatitis, and panel B focuses on of the age-standardized DALYs rate in pancreatitis. There are four columns, each corresponding to a different age group: the first for those under 5 years old, the second for 5–9 years old, the third for 10–14 years old and the fourth for 15–19 years old. In the bar charts, blue represents male data, and red represents female data. GBD: global burden of diseases, injuries, and risk factors study; DALYs: disability-adjusted life year; SDI: socio-demographic index. The number, age-standardized rate and temporal trend of pancreatitis in children and adolescents from 1990 to 2021. ASDR: age-standardized death rate; DALYs: disability-adjusted life years; EAPC: estimated annual percentage change; SDI: socio-demographic index. In 2021, an estimated 39.12 child and adolescent deaths were due to alcoholic pancreatitis, comprising 3.51% of global pancreatitis-related fatalities ( Table S5 ). Males had a higher proportion at 4.66%, compared to 1.61% in females. Globally, males bore a significantly higher burden of alcohol-attributed pancreatitis death across all regions ( Figure S4 ). Regional variations show that Eastern Europe, Central Europe and Southern Latin America have the highest disease burden due to alcohol consumption. In contrast, North Africa and the Middle East, along with Oceania, report lower alcohol-attributed death rates across all age groups. Death rates generally decline as SDI values increase in most regions and countries ( Figures 4(A) and 5(A) ). However, exceptions exist. For instance, in Eastern Europe, the death rate peaks at an SDI value of 0.594 in 2009 before declining, after initially increasing significantly with higher SDI. The global death rate has gradually declined from 1990 to 2021, especially in regions with higher SDI. In low-middle SDI regions, death rates significantly increased from 1990 to 1995, then stabilized until 2005, before declining ( Figure S5A ). The relationship between death and SDI varies significantly by region and country ( Figures 4(A) and 5(A) ). In Southern Sub-Saharan Africa, death rates rise with increasing SDI, while in Australasia and Western Europe, they decrease with higher SDI values. Similar trends are observed in the relationship between DALYs rate and SDI at the regional and national levels ( Figure 4(B) and 5(B) and Figure S5B ). The ASDR (A) and age-standardized DALYs rate of pancreatitis in children and adolescents by 21 GBD regions and SDI, 1990–2021. The solid line represents expected values calculated from SDI and aggregate disease rates. Thirty-two data points per region depict observed rates for each year. Points above and below the line indicate higher and lower-than-expected disease burdens, respectively. GBD: global burden of diseases, injuries, and risk factors study; SDI: sociodemographic index; ASDR: age-standardized death rate; DALY: disability-adjusted-life-year. The ASDR (A) and age-standardized DALYs rate (B) of pancreatitis in children and adolescents by 204 countries and SDI, 1990–2021. The solid line represents expected values calculated from SDI and aggregate disease rates. Thirty-two data points per region depict observed rates for each year; the shaded area shows the 95% confidence interval of these estimates. Points above and below the line indicate higher and lower-than-expected disease burdens, respectively. GBD: global burden of diseases, injuries, and risk factors study; SDI: sociodemographic index; ASDR: age-standardized death rate; DALY: disability-adjusted-life-year. The projection from 2022 to 2035 forecasts a slow decline in global pancreatitis-related deaths among children and adolescents, with males expected to continue having higher fatality rates than females ( Figure 6 ). Female deaths are projected to decrease from 430.60 in 2022 to 259.63 in 2030, while male deaths are expected to rise from 727.75 to 610.34 ( Table S6 ). An annual decline in the global ASDR is projected ( Table S7 ). The observation and prediction of the number of deaths (A) and ASDR (B) from pancreatitis in children and adolescents from 1990 to 2035. The first column represents both sex group; the second column represents the male group; the third column represents the female group. The black dotted lines depict the observed values of the number of deaths or the ASDR for pancreatitis in children and adolescents from 1990 to 2021. The red dashed lines illustrate the predicted values for the same metrics from 2022 to 2035. The light blue shaded areas, arranged from the innermost to the outermost, represent the 70%, 80%, 90% and 95% confidence intervals of these estimates, respectively. SDI: socio-demographic index; GBD: global burden of diseases, injuries, and risk factors study; DALY: disability-adjusted life-year.

AP and CP differ significantly in terms of progression and prognosis. The transition from AP to CP, particularly in adolescents, highlights the urgent need for early diagnosis and intervention to prevent long-term complications [ 3 , 13 ]. Severe acute pancreatitis (SAP) remains a major clinical challenge due to its potential for multi-organ failure and high mortality rates. Although the overall incidence of pancreatitis in children and adolescents has decreased, SAP continues to represent a critical concern. Timely interventions, including fluid resuscitation, nutritional support, and, when necessary, surgical management, are essential to prevent organ failure and reduce mortality [ 14 , 15 ]. Recurrent episodes of AP can lead to CP, further increasing the risk of pancreatic insufficiency and progression to pancreatic cancer. To our knowledge, this study is the first to provide comprehensive global, regional and national insights into the burden of pancreatitis and its associated risk factors among individuals under 20 from 1990 to 2021, with projections for the subsequent 13 years. Recent therapeutic advancements aimed at reducing mortality in SAP have focused on early biomarkers for diagnosis, personalized treatment protocols and novel pharmacological agents. These strategies show promise in improving outcomes for SAP patients. Ongoing research is essential for further developing effective therapies to reduce the burden of SAP and enhance patient prognosis. Additionally, our findings identify alcohol-related deaths as a leading risk factor for pancreatitis across various regions, underscoring the need for targeted public health interventions. The global adolescent population, now exceeding 1.3 billion, accounts for 16% of the world’s total population, with projections for continued growth, particularly in low- and middle-income countries [ 9 , 16 ]. As the number of children and adolescents rises, the burden of pancreatitis in this demographic is expected to increase, posing significant challenges to prevention and treatment efforts, especially in regions with limited medical resources [ 17 ]. While the ASDR and age-standardized DALYs rate for pancreatitis have declined globally, this trend is expected to continue through 2035. Alcohol remains a key etiological factor in AP, accounting for 17–25% of global cases, with a higher proportion in low- and middle-income countries, where alcohol abuse contributes to 35% of AP and 70% of CP cases [ 18 ]. Notably, CP carries a 20-fold increased risk of pancreatic cancer, which has a poor prognosis [ 19 ]. Our findings show that alcohol contributes to 3.51% of pancreatitis-related deaths in children and adolescents. Although the death rate from alcoholic pancreatitis in youth is lower than in adults, the challenges of delayed diagnosis and treatment in this age group often exacerbate the severity of outcomes [ 20 ]. Children and adolescents present with atypical symptoms, hindering early detection, and are at higher risk of complications such as pancreatic insufficiency and CP progression [ 21 , 22 ]. Severe complications, including pancreatic necrosis and infections, increase hospitalization time, healthcare costs and mortality risk [ 23 ]. Promoting early diagnosis, improving treatment strategies and fostering multidisciplinary care are essential to reducing death risk and improving long-term outcomes for paediatric pancreatitis [ 5 , 24 ]. The regional disparities in paediatric pancreatitis burden require urgent attention. Among the 21 GBD regions, Eastern Europe, Central Europe and Southern Latin America exhibited the highest increases in ASDR and DALYs. These trends are primarily linked to alcohol consumption patterns, with Eastern and Central Europe recognized as global leaders in alcohol-related health risks [ 25 ]. In 2021, these regions ranked highest in alcohol consumption among nearly 200 WHO member states, underscoring the pervasive role of alcohol in health outcomes [ 26 ]. Similarly, Southern Latin America reports higher alcohol consumption than other Latin American regions [ 27 ]. Cultural, historical and educational factors shape drinking behaviours, highlighting the need for sustainable alcohol control policies to reduce alcohol-attributed mortality and improve health outcomes [ 28 ]. Substantial international disparities are also evident in paediatric pancreatitis, with Tokelau, Niue and Guatemala reporting the highest death and DALYs rate. For island nations like Tokelau and Niue, traditional diets high in fat and sugar, coupled with elevated alcohol consumption, contribute to increased pancreatitis risk [ 29 , 30 ]. Addressing these disparities requires international cooperation and targeted interventions, particularly in low SDI countries, to mitigate health inequities and improve paediatric health outcomes globally. This study found males had a higher pancreatitis burden than females in both 1990 and 2021. This disparity reflects not only biological differences but also a complex mix of lifestyle, dietary habits and sociocultural factors. Female pancreatitis is mainly linked to gallstones, autoimmune diseases and idiopathic causes, while male pancreatitis often relates to alcohol consumption [ 31 , 32 ]. Some research indicates female physiological traits, like oestrogen levels, might protect against alcohol-induced pancreatitis [ 33 ]. Males generally drink more frequently than females. Also, male post-alcohol consumption behaviours like binge drinking may raise their pancreatitis risk, contributing to the observed gender disease differences [ 34 ]. Research into these disparities benefits clinical practice and guides public health policy in targeting preventative measures and treatment strategies by gender. The burden of pancreatitis varies significantly across paediatric age groups, with age serving as a critical determinant of both incidence and mortality. Notably, the 15–19 age group bears the heaviest burden of pancreatitis, which is likely linked to shifts in lifestyle, rising obesity rates, dietary habits and increasing alcohol consumption [ 4 , 35 ]. As children and adolescents progress through critical developmental stages, the etiological factors contributing to AP evolve. In younger children, genetic predispositions and trauma are predominant [ 6 ], while in older age groups, lifestyle factors such as obesity and alcohol use play a more significant role [ 7 , 8 ]. Given the rising prevalence of these risk factors and the critical transition period between 15 and 19 years, it is essential for public health strategies to focus on health education, lifestyle modification, dietary improvements and alcohol consumption control. Promoting awareness among adolescents about the importance of a balanced diet, regular physical activity, and the avoidance of alcohol abuse is crucial to reducing pancreatitis incidence and improving long-term outcomes. In most regions, there has been a significant decline in both the mortality and DALYs rate of pancreatitis among children and adolescents. However, it is noteworthy that from 1990 to 2021, Southern Sub-Saharan Africa experienced an increase in both death and DALYs rate, despite an increase in SDI values. This paradoxical situation persists even with higher SDI scores and advancements in medical facilities, as Southern Sub-Saharan Africa continues to grapple with a shortage of medical resources in certain areas [ 36 ]. This surge in pancreatitis rates may be linked to lifestyle changes, such as the adoption of a Western diet and a rise in alcohol consumption. These factors could potentially elevate the incidence of pancreatitis, thereby indirectly increasing mortality rates [ 37 ]. This study has several limitations: (1) the availability of high-quality, detailed data is limited in certain regions, particularly low-income countries, which may affect the generalizability of the findings. (2) Due to data constraints, an in-depth analysis of specific types of pancreatitis, such as acute versus chronic forms, was not possible. Future research should aim to classify pancreatitis based on histological distinctions to enhance our understanding of disease progression. (3) While infections and pancreaticobiliary diseases contribute to pancreatitis pathogenesis, the GBD 2021 dataset only permits an analysis of alcohol-attributable disease burden, limiting the scope of our findings.

In summary, globally, pancreatitis-related deaths, DALYs, ASDR and age-standardized DALYs rate in children and adolescents are gradually declining, with this trend expected to continue to 2035. Alcohol consumption significantly contributes to the pancreatitis burden among children and adolescents globally. Accordingly, our findings underscore the urgent need to refine and enhance strategies to target alcohol consumption via effective national policies. These policies must consider gender, age and regional variations. Further research is needed on other pancreatitis risk factors in children and adolescents. Moreover, establishing comprehensive surveillance and treatment programs in less developed regions is crucial for alleviating alcohol-induced pancreatitis.