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Ranking of causes of death in females and males. The causes are sorted according to their ranking at the global level. The color coding indicates the relative ranking of each cause, with red the highest and green the lowest. The s appearing in each column indicate the geography-specific ranking of that cause in Blanks indicate causes that were not contracted in that geographical area. HIV indicates human immunodeficiency virus. This figure shows the rankings for the top 25 causes of global disability-adjusted life years among children and adolescents 19 years or younger at the global level in, and Lines connecting the boxes illustrate changes in ranking.

Any cause that appears in the top 25 in any year is listed, along with its ranking during each year. Group I causes infectious, neonatal, nutritional, and maternal are shown in gray, noncommunicable diseases in red, and injuries in green. Statistically ificant differences appear in bold. Each geography is ased an SDI value for each year, and nonlinear spline regressions are used to find the average relationship between SDI and cause-specific burden rates.

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Each geographical area is ased an SDI value for each year, and nonlinear spline regressions are used to find the mean association between SDI and cause-specific rates of disease burden. Global pregnancy complication ratio events per live births by type of complication and age group in JAMA Pediatr. Question What are the levels and trends of mortality and nonfatal health loss among children and adolescents from to ? Findings This study found ificant global decreases in all-cause child and adolescent mortality from tobut with increasing global inequality.

In countries with a low Socio-demographic Index SDImortality is the primary driver of health loss in children and adolescents, largely owing to infectious, nutritional, maternal, and neonatal causes, while nonfatal health loss prevails in locations with a higher SDI. Meaning Nations should evaluate drivers of disease burden among children and adolescents to aid implementation of appropriate strategies to maximize the health of populations.

Importance Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health. Objective To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from to to provide a framework for policy discussion.

Evidence Review Cause-specific mortality and nonfatal health outcomes were analyzed for countries and territories by age group, sex, and year from to using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed Socio-demographic Index [SDI] for each geographic unit and year, which evaluates the historical association between SDI and health loss.

Findings Global child and adolescent mortality decreased from Most deaths in occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden.

The absolute burden of disability in children and adolescents increased 4. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth eg, neonatal disorders, congenital birth defects, and hemoglobinopathies and complications of a variety of infections and nutritional deficiencies.

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Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

Conclusions and Relevance Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

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Reducing mortality among children younger than 5 years has been a focus of ificant international attention for several decades, beginning with the Convention on the Rights of the Child, accelerating during the Millennium Development Goal era, and continuing with the Sustainable Development Goals SDGs. High return on investment is expected when evidence-based interventions are implemented to address the health and well-being of children and adolescents.

We present separately by sex, describe the epidemiologic factors of several highly disabling conditions that arise from multiple GBD causes, report levels and trends in pregnancy complications among adolescents, and evaluate the association between metrics of disease burden and the Socio-demographic Index SDIa composite indicator of development status generated for GBD Briefly, we quantified an extensive set of health loss metrics—with corresponding uncertainty intervals UIs —from to for 20 age groups and both sexes in countries and territories.

For the present study, we further analyzed levels and trends for children and adolescents 19 years or younger, which includes the first 7 age groups of the GBD analyses. Health loss metrics in this analysis include all-cause mortality, cause-specific mortality deaths and years of life lost [YLLs]nonfatal health outcomes prevalence and years lived with disability [YLDs]and total disease burden disability-adjusted life years [DALYs].

Countries and territories were hierarchically organized into 21 regions and 7 super-regions, which are aggregates of the 21 regions in the GBD location hierarchy. The GBD cause list organizes all diseases and injuries into a 4-level hierarchy. The first level has 3 : 1 communicable, maternal, neonatal, and nutritional disorders group I conditions ; 2 NCDs; and 3 injuries. Level 2 of the hierarchy has 21 cause groups, while levels 3 causes and 4 causes contain more disaggregated causes and cause groups.

Our all-cause and cause-specific mortality analyses used systematic approaches to address data challenges such as variation in both death certification practices and coding schemes, inconsistent age group reporting, and misclassification of human immunodeficiency virus HIV or AIDS. Each death was ased to a single underlying cause. Cause-of-death ensemble modeling was the most widely used statistical tool for estimating cause-specific mortality across GBD Cause-of-death ensemble modeling uses a train-test-test approach to evaluate a wide range of families of statistical models, maximizing out-of-sample predictive validity of final models.

Years of life lost were calculated by multiplying counts of age-specific death and normative life expectancy at the age of death. Analyses of nonfatal health outcomes used detailed epidemiologic data from systematic reviews of the literature, hospital and claims databases, health surveys, case notification systems, cohort studies, and disease-specific registries. DisMod-MR 2. Finally, we adjusted for comorbid illness using a microsimulation framework within each population and proportionally adjusting YLDs for each comorbid condition.

We developed the SDI for GBDas described ly, to characterize epidemiologic transitions more robustly than is possible with analyses based only on income. Socio-demographic Index scores were scaled from 0 highest fertility, lowest income, and lowest education to 1 highest income, highest education, and lowest fertilityand each geographical unit was ased an SDI score for each year.

For comparisons across SDI quintiles, each geographical unit was ased to a single quintile according to its SDI in eFigure 1 in the Supplement. Cumulative and annualized rates of change were calculated on point estimates, and corresponding UIs were derived from the same calculations performed at the draw level.

We present as both total s to illustrate the absolute magnitude of burden, and all-age rates, to compare across geographical areas with differently sized populations. We completed age standardization for ages 19 years or younger for the 10 highest-ranked global causes of death and disability to help compare across populations with different age structures; all other are presented as total and all-ages rates only. for the global level, along with SDI quintile and region in order of decreasing SDI, are presented in the main article. Corresponding country-levelwith uncertainty and cumulative percent change, are in eTable 1 in the Supplement for children and adolescents 19 years or younger and eTable 2 in the Supplement for children and adolescents 5 years or younger.

Inthere were 7. As can be seen in Table 1mortality in children and adolescents 19 years or younger decreased in all SDI quintiles, but inequality increased. South Asia ed for 2. Next were Western sub-Saharan Africa 1. As seen in Table 1 across the entire age range, rankings were dominated by those affecting the youngest children. Globally, the most common causes of death were neonatal preterm birth complications mortality rate, With the exception of the infectious causes malaria, diarrheal diseases, and meningitis each cause was highly ranked in all regions.

Rankings of the 25 leading level 3 causes of death among children and adolescents 19 years or younger, disaggregated by sex, are shown in Figure 1. Besides the causes listed above, others ranking in the top 10 in specific regions included hemoglobinopathies and hemolytic anemias in Western sub-Saharan Africa, where sickle cell disease is the largest level 4 cause of hemoglobinopathiesas well as selected infections measles, HIV and AIDS, whooping cough, intestinal infectious disease, sexually transmitted infections excluding HIV [ie, congenital syphilis], and encephalitis and injuries drowning, road injuries, direct effects of war [ie, collective violence] and natural disasters, exposure to mechanical forces, aspiration of a foreign body, and fire.

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We found important differences in mortality patterns for each of the 7 component age groups 19 years or younger in eFigure 2A-G in the Supplement. During the neonatal period ie, 6 days or less and daysrankings across SDI quintiles and regions were broadly similar; mortality was dominated by neonatal complications, congenital anomalies, and LRIs.

Divergence began to appear during the postneonatal period ie, dayswhen acquired infections such as LRIs, diarrhea, malaria, and meningitis predominated in lower-SDI geographical areas and congenital anomalies and sudden infant death syndrome predominated in higher-SDI geographical areas.

Protein-energy malnutrition also emerged as an important cause of death in the postneonatal period in several regions, especially in males, a trend that continued into children aged 1 to 4 years, where it ranked fourth globally in both sexes. Malaria, LRIs, and diarrhea were the 3 highest-ranked causes of death in children aged 1 to 4 years; because protein-energy malnutrition and other forms of malnutrition raise the mortality risk for each, the effect of malnutrition is even higher than that reflected in for protein-energy malnutrition alone. Geographic heterogeneity was also observed in other causes of death in children aged 1 to 4 years for both females and males at the global level, including measles concentrated in the lowest 3 SDI quintiles, particularly Oceania and Southeast Asialeukemia, road injuries, and drowning all concentrated in the 3 highest SDI quintiles.

Geographical differences in causes of death in were more pronounced with increasing age ie, years, years, and years. Congenital anomalies and cancers leukemia, brain cancer, and other neoplasms [eg, sarcomas] were highly ranked in high-SDI regions in all age groups, simultaneously reflecting continued risk of mortality beyond the time of initial diagnosis and lower overall risk of mortality in the population. Intestinal infectious disease was highly ranked globally second in children aged years for both males and femalesdriven primarily by very large mortality s in South Asia and Southeast Asia.

Human immunodeficiency virus and AIDS rose to be ranked first globally among children aged 10 to 14 years, driven almost entirely by epidemics in the Caribbean and sub-Saharan Africa. Diarrhea, LRIs, malaria, and protein-energy malnutrition remained important causes of death throughout all age groups but were largely limited except in geographical areas with lower SDIs. Five level 3 causes of maternal mortality—hemorrhage, hypertensive disorders, indirect causes, other direct causes, and the combined category of abortion, ectopic pregnancy, and miscarriage—were in the top 25 causes of maternal mortality globally in females aged 15 to 19 years, reflecting the high burden of maternal mortality among adolescents in the 2 lowest SDI quintiles.

The ranking of injuries as causes of death increased consistently with age and with increasing SDI; all injuries except self-harm ranked higher in males than females. Road injuries were the leading injury-associated cause of death in all age groups, rising to first globally among all causes for both sexes in adolescents aged 15 to 19 years. Drowning was the next highest-ranked cause of injury-associated death in children aged 5 to 9 years ninth overall among females and sixth among males and 10 to 14 years eighth overall in females and third in maleswhile self-harm second overall in females and third in males and interpersonal violence 14th overall in females and second in males were the next most common injury-associated causes of death among adolescents aged 15 to 19 years.

The direct mortality burden of war was extremely large in North Africa and the Middle East, where it ranked second for each sex among children aged 1 to 4 years and first in all subsequent age groups in Corresponding country-level for andwith uncertainty and mean annualized rates of change, are in eTable 3 in the Supplement for children and adolescents 19 years or younger and eTable 4 in the Supplement for children 5 years or younger. Iron-deficiency anemia was the highest-ranking level 3 cause of YLDs in children and adolescents, followed by skin and subcutaneous diseases, asthma, hemoglobinopathies and hemolytic anemias, diarrheal diseases, congenital anomalies, protein-energy malnutrition, epilepsy, malaria, and neonatal complications of preterm birth.

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Among children 5 years or younger, there was higher relative importance of disability owing to protein-energy malnutrition third highest-ranking cause and diarrheal diseases fourth highest-ranking causeas well as neonatal encephalopathy ninth highest-ranking cause and other neonatal disorders tenth highest-ranking cause. Although the age-standardized prevalence and rate of YLDs decreased for most conditions, it increased for malaria and congenital anomalies.

The burden of most conditions either decreased with increasing SDI or was relatively constant across different SDI quintiles. Two exceptions were congenital anomalies, which increased with increasing SDI, and hemoglobinopathies, which were highest in low- to middle-SDI geographical areas. Many clinical conditions cause ificant disease burden in children and adolescents, but because they can arise from multiple causes, their effect is not obvious when examining causes of GBD.

Examples that would be in the top 10 global causes of YLDs if considered alone are anemia, developmental intellectual disability, epilepsy, hearing loss, and vision loss. For example, while iron-deficiency anemia was the leading level 3 cause of disability, it ed for only about two-thirds of total anemia in children and adolescents 19 years or younger in eTable 5 in the Supplementand each case tended to be less severe than other etiologic causes of anemia.

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Infectious diseases, hemoglobinopathies, malaria, hookworm, gynecologic conditions, and gastritis and duodenitis were other important causes of anemia in children and adolescents. Neonatal disorders were the most common nonidiopathic cause of both developmental intellectual disability eTable 6 in the Supplement and epilepsy eTable 7 in the Supplement. Autism, iodine deficiency, and congenital disorders were important causes of intellectual disability, while much of the rest of intellectual disability and much of nonidiopathic epilepsy were secondary to infectious causes, especially malaria and meningitis.

Hearing and vision loss also contributed to the disease burden within children and adolescents 19 years or younger, with age-associated and other hearing loss ing for most hearing loss burden eTable 8 in the Supplement. For vision loss, a range of causes contributed to the burden among children and adolescents 19 years or younger, including neonatal disorders and nutritional deficiencies eTable 9 in the Supplement. Mortality was the primary driver of health loss owing to maternal disorders in adolescents. The mean annualized decline in the maternal mortality ratio among adolescents aged 10 to 19 years was only 1.

Maternal hemorrhage was the highest-ranked level 3 cause of maternal mortality globally, driven largely by its prominence in low-SDI geographical areas where teenage pregnancy and the burden of maternal mortality are the highest eFigures 3 and 4 in the Supplement.

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