Changes in stillbirths and child and youth mortality in 2020 and 2021 during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has been extensively studied for its impact on mortality, particularly in older age groups. However, the pandemic effects on stillbirths and mortality rates in neonates, infants, children and youth remain poorly understood. This study comprehensively analyses the pandemic influence on young mortality and stillbirths across 112 countries and territories in 2020 and 104 in 2021. METHODS: Using data from civil registers and vital statistics systems (CRVS) and the Health Management Information System (HMIS), we estimate expected mortality levels in a non-pandemic setting and relative mortality changes (p-scores) through generalized linear models. The analysis focuses on the distribution of country-specific mortality changes and the proportion of countries experiencing deficits, no changes and excess mortality in each age group. RESULTS: Results show that stillbirths and under-25 mortality were as expected in most countries during 2020 and 2021. However, among countries with changes, more experienced deficits than excess mortality, except for stillbirths, neonates and those aged 10-24 in 2021, where, despite the predominance of no changes, excess mortality prevailed. Notably, a fifth of examined countries saw increases in stillbirths and a quarter in young adult mortality (20-24) in 2021. Our findings are highly consistent between females and males and similar across income levels. CONCLUSION: Despite global disruptions to essential services, stillbirths and youth mortality were as expected in most observed countries, challenging initial hypotheses. However, the study suggests the possibility of delayed adverse effects that require more time to manifest at the population level. Understanding the lasting impacts of the COVID-19 pandemic requires ongoing, long-term monitoring of health and deaths among children and youth, particularly in low- and lower-middle-income countries.

Sex differences in mortality among children, adolescents, and young people aged 0-24 years: a systematic assessment of national, regional, and global trends from 1990 to 2021.

BACKGROUND: Differences in mortality exist between sexes because of biological, genetic, and social factors. Sex differentials are well documented in children younger than 5 years but have not been systematically examined for ages 5-24 years. We aimed to estimate the sex ratio of mortality from birth to age 24 years and reconstruct trends in sex-specific mortality between 1990 and 2021 for 200 countries, major regions, and the world. METHODS: We compiled comprehensive databases on the mortality sex ratio (ratio of male to female mortality rates) for individuals aged 0-4 years, 5-14 years, and 15-24 years. The databases contain mortality rates from death registration systems, full birth and sibling histories from surveys, and reports on household deaths in censuses. We modelled the sex ratio of age-specific mortality as a function of the mortality in both sexes using Bayesian hierarchical time-series models. We report the levels and trends of sex ratios and estimate the expected female mortality and excess female mortality rates (the difference between the estimated female mortality and the expected female mortality) to identify countries with outlying sex ratios. FINDINGS: Globally, the mortality sex ratio was 1·13 (ie, boys were more likely to die than girls of the same age) for ages 0-4 years (90% uncertainty interval 1·11 to 1·15) in 2021. This ratio increased with age to 1·16 (1·12 to 1·20) for 5-14 years, reaching 1·65 for 15-24 years (1·52 to 1·75). In all age groups, the global sex ratio of mortality increased between 1990 and 2021, driven by faster declines in female mortality. In 2021, the probability of a newborn male reaching age 25 years was 94·1% (93·7 to 94·4), compared with 95·1% for a newborn female (94·7 to 95·3). We found a disadvantage of females versus males (compared with countries with similar total mortality) in 2021 in five countries for ages 0-4 years (Algeria, Bangladesh, Egypt, India, and Iran), one country (Suriname) for ages 5-14 years, and 13 countries for ages 15-24 years (including Bangladesh and India). We found the reverse pattern (disadvantage of males vs females compared with countries of similar total mortality) in one country in ages 0-4 years (Vietnam) and eight countries in ages 15-24 years (including Brazil and Mexico). Globally, the number of excess female deaths from birth to age 24 years was 86 563 (-6059 to 164 000) in 2021, down from 544 636 (453 982 to 633 265) in 1990. INTERPRETATION: The global sex ratio of mortality for all age groups in the first 25 years of life increased between 1990 and 2021. Targeted interventions should focus on countries with outlying sex ratios of mortality to reduce disparities due to discrimination in health care, nutrition, and violence. FUNDING: The Bill & Melinda Gates Foundation, US Agency for International Development, and King Abdullah University of Science and Technology.

Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation.

BACKGROUND: The Sustainable Development Goals (SDGs), set in 2015 by the UN General Assembly, call for all countries to reach an under-5 mortality rate (U5MR) of at least as low as 25 deaths per 1000 livebirths and a neonatal mortality rate (NMR) of at least as low as 12 deaths per 1000 livebirths by 2030. We estimated levels and trends in under-5 mortality for 195 countries from 1990 to 2019, and conducted scenario-based projections of the U5MR and NMR from 2020 to 2030 to assess country progress in, and potential for, reaching SDG targets on child survival and the potential under-5 and neonatal deaths over the next decade. METHODS: Levels and trends in under-5 mortality are based on the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database on under-5 mortality, which contains around 18 000 country-year datapoints for 195 countries-nearly 10 000 of those datapoints since 1990. The database includes nationally representative mortality data from vital registration systems, sample registration systems, population censuses, and household surveys. As with previous sets of national UN IGME estimates, a Bayesian B-spline bias-reduction model (B3) that considers the systematic biases associated with the different data source types was fitted to these data to generate estimates of under-5 (age 0-4 years) mortality with uncertainty intervals for 1990-2019 for all countries. Levels and trends in the neonatal mortality rate (0-27 days) are modelled separately as the log ratio of the neonatal mortality rate to the under-5 mortality rate using a Bayesian model. Estimated mortality rates are combined with livebirths data to calculate the number of under-5 and neonatal deaths. To assess the regional and global burden of under-5 deaths in the present decade and progress towards SDG targets, we constructed several scenario-based projections of under-5 mortality from 2020 to 2030 and estimated national, regional, and global under-5 mortality trends up to 2030 for each scenario. FINDINGS: The global U5MR decreased by 59% (90% uncertainty interval [UI] 56-61) from 93·0 (91·7-94·5) deaths per 1000 livebirths in 1990 to 37·7 (36·1-40·8) in 2019, while the annual number of global under-5 deaths declined from 12·5 (12·3-12·7) million in 1990 to 5·2 (5·0-5·6) million in 2019-a 58% (55-60) reduction. The global NMR decreased by 52% (90% UI 48-55) from 36·6 (35·6-37·8) deaths per 1000 livebirths in 1990, to 17·5 (16·6-19·0) in 2019, and the annual number of global neonatal deaths declined from 5·0 (4·9-5·2) million in 1990, to 2·4 (2·3-2·7) million in 2019, a 51% (47-54) reduction. As of 2019, 122 of 195 countries have achieved the SDG U5MR target, and 20 countries are on track to achieve the target by 2030, while 53 will need to accelerate progress to meet the target by 2030. 116 countries have reached the SDG NMR target with 16 on track, leaving 63 at risk of missing the target. If current trends continue, 48·1 million under-5 deaths are projected to occur between 2020 and 2030, almost half of them projected to occur during the neonatal period. If all countries met the SDG target on under-5 mortality, 11 million under-5 deaths could be averted between 2020 and 2030. INTERPRETATION: As a result of effective global health initiatives, millions of child deaths have been prevented since 1990. However, the task of ending all preventable child deaths is not done and millions more deaths could be averted by meeting international targets. Geographical and economic variation demonstrate the possibility of even lower mortality rates for children under age 5 years and point to the regions and countries with highest mortality rates and in greatest need of resources and action. FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

Global, regional, and national mortality trends in youth aged 15-24 years between 1990 and 2019: a systematic analysis.

BACKGROUND: The global health community is devoting considerable attention to adolescents and young people, but risk of death in this population is poorly measured. We aimed to reconstruct global, regional, and national mortality trends for youths aged 15-24 years between 1990 and 2019. METHODS: In this systematic analysis, we used all publicly available data on mortality in the age group 15-24 years for 195 countries, as compiled by the UN Inter-agency Group for Child Mortality Estimation. We used nationally representative vital registration data, estimated the completeness of death registration, and extracted mortality rates from surveys with sibling histories, household deaths reported in censuses, and sample registration systems. We used a Bayesian B-spline bias-reduction model to generate trends in 10q15, the probability that an adolescent aged 15 years would die before reaching age 25 years. This model treats observations of the 10q15 probability as the product of the actual risk of death and an error multiplier that varies depending on the data source. The main outcome that we assessed was the levels of and trends in youth mortality and the global and regional mortality rates from 1990 to 2019. FINDINGS: Globally, the probability of an individual dying between age 15 years and 24 years was 11·2 deaths (90% uncertainty interval [UI] 10·7-12·5) per 1000 youths aged 15 in 2019, which is about 2·5 times less than infant mortality (28·2 deaths [27·2-30·0] by age 1 year per 1000 live births) but is higher than the risk of dying from age 1 to 5 (9·7 deaths [9·1-11·1] per 1000 children aged 1 year). The probability of dying between age 15 years and 24 years declined by 1·4% per year (90% UI 1·1-1·8) between 1990 and 2019, from 17·1 deaths (16·5-18·9) per 1000 in 1990; by contrast with this total decrease of 34% (27-41), under-5 mortality declined by 59% (56-61) in this period. The annual number of deaths declined from 1·7 million (90% UI 1·7-1·9) in 1990 to 1·4 million (1·3-1·5) in 2019. In sub-Saharan Africa, the number of deaths increased by 20·8% from 1990 to 2019. Although 18·3% of the population aged 15-24 years were living in sub-Saharan Africa in 2019, the region accounted for 37·9% (90% UI 34·8-41·9) of all worldwide deaths in youth. INTERPRETATION: It is urgent to accelerate progress in reducing youth mortality. Efforts are particularly needed in sub-Saharan Africa, where the burden of mortality is increasingly concentrated. In the future, a growing number of countries will see youth mortality exceeding under-5 mortality if current trends continue. FUNDING: UN Children's Fund, Bill & Melinda Gates Foundation, United States Agency for International Development.

Global, regional, and national mortality trends in older children and young adolescents (5-14 years) from 1990 to 2016: an analysis of empirical data.

BACKGROUND: From 1990 to 2016, the mortality of children younger than 5 years decreased by more than half, and there are plentiful data regarding mortality in this age group through which we can track global progress in reducing the under-5 mortality rate. By contrast, little is known on how the mortality risk among older children (5-9 years) and young adolescents (10-14 years) has changed in this time. We aimed to estimate levels and trends in mortality of children aged 5-14 years in 195 countries from 1990 to 2016. METHODS: In this analysis of empirical data, we expanded the United Nations Inter-agency Group for Child Mortality Estimation database containing data on children younger than 5 years with 5530 data points regarding children aged 5-14 years. Mortality rates from 1990 to 2016 were obtained from nationally representative birth histories, data on household deaths reported in population censuses, and nationwide systems of civil registration and vital statistics. These data were used in a Bayesian B-spline bias-reduction model to generate smoothed trends with 90% uncertainty intervals, to determine the probability of a child aged 5 years dying before reaching age 15 years. FINDINGS: Globally, the probability of a child dying between the ages 5 years and 15 years was 7·5 deaths (90% uncertainty interval 7·2-8·3) per 1000 children in 2016, which was less than a fifth of the risk of dying between birth and age 5 years, which was 41 deaths (39-44) per 1000 children. The mortality risk in children aged 5-14 years decreased by 51% (46-54) between 1990 and 2016, despite not being specifically targeted by health interventions. The annual number of deaths in this age group decreased from 1·7 million (1·7 million-1·8 million) to 1 million (0·9 million-1·1 million) in 1990-2016. In 1990-2000, mortality rates in children aged 5-14 years decreased faster than among children aged 0-4 years. However, since 2000, mortality rates in children younger than 5 years have decreased faster than mortality rates in children aged 5-14 years. The annual rate of reduction in mortality among children younger than 5 years has been 4·0% (3·6-4·3) since 2000, versus 2·7% (2·3-3·0) in children aged 5-14 years. Older children and young adolescents in sub-Saharan Africa are disproportionately more likely to die than those in other regions; 55% (51-58) of deaths of children of this age occur in sub-Saharan Africa, despite having only 21% of the global population of children aged 5-14 years. In 2016, 98% (98-99) of all deaths of children aged 5-14 years occurred in low-income and middle-income countries, and seven countries alone accounted for more than half of the total number of deaths of these children. INTERPRETATION: Increased efforts are required to accelerate reductions in mortality among older children and to ensure that they benefit from health policies and interventions as much as younger children. FUNDING: UN Children's Fund, Bill & Melinda Gates Foundation, United States Agency for International Development.

Probabilistic population projections for countries with generalized HIV/AIDS epidemics.

In 2015, the United Nations (UN) issued probabilistic population projections for all countries up to 2100, by simulating future levels of total fertility and life expectancy and combining the results using a standard cohort component projection method. For the 40 countries with generalized HIV/AIDS epidemics, the mortality projections used the Spectrum/Estimation and Projection Package (EPP) model, a complex, multistate model designed for short-term projections of policy-relevant quantities for the epidemic. We propose a simpler approach that is more compatible with existing UN projection methods for other countries. Changes in life expectancy are projected probabilistically using a simple time series regression and then converted to age- and sex-specific mortality rates using model life tables designed for countries with HIV/AIDS epidemics. These are then input to the cohort component method, as for other countries. The method performed well in an out-of-sample cross-validation experiment. It gives similar short-run projections to Spectrum/EPP, while being simpler and avoiding multistate modelling.

Correction: A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model.

[This corrects the article DOI: 10.1371/journal.pone.0154774.].

Insights into mortality patterns and causes of death through a process point of view model.

Process point of view (POV) models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process POV, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the twentieth century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed.

Quantifying Intrinsic and Extrinsic Contributions to Human Longevity: Application of a Two-Process Vitality Model to the Human Mortality Database.

The rise in human life expectancy has involved declines in intrinsic and extrinsic mortality processes associated, respectively, with senescence and environmental challenges. To better understand the factors driving this rise, we apply a two-process vitality model to data from the Human Mortality Database. Model parameters yield intrinsic and extrinsic cumulative survival curves from which we derive intrinsic and extrinsic expected life spans (ELS). Intrinsic ELS, a measure of longevity acted on by intrinsic, physiological factors, changed slowly over two centuries and then entered a second phase of increasing longevity ostensibly brought on by improvements in old-age death reduction technologies and cumulative health behaviors throughout life. The model partitions the majority of the increase in life expectancy before 1950 to increasing extrinsic ELS driven by reductions in environmental, event-based health challenges in both childhood and adulthood. In the post-1950 era, the extrinsic ELS of females appears to be converging to the intrinsic ELS, whereas the extrinsic ELS of males is approximately 20 years lower than the intrinsic ELS.

A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model.

Twin studies that focus on the correlation in age-at-death between twin pairs have yielded important insights into the heritability and role of genetic factors in determining lifespan, but less attention is paid to the biological and social role of zygosity itself in determining survival across the entire life course. Using data from the Danish Twin Registry and the Human Mortality Database, we show that monozygotic twins have greater cumulative survival proportions at nearly every age compared to dizygotic twins and the Danish general population. We examine this survival advantage by fitting these data with a two-process mortality model that partitions survivorship patterns into extrinsic and intrinsic mortality processes roughly corresponding to acute, environmental and chronic, biological origins. We find intrinsic processes confer a survival advantage at older ages for males, while at younger ages, all monozygotic twins show a health protection effect against extrinsic death akin to a marriage protection effect. While existing research suggests an increasingly important role for genetic factors at very advanced ages, we conclude that the social closeness of monozygotic twins is a plausible driver of the survival advantage at ages <65.

Modeling age-specific mortality for countries with generalized HIV epidemics.

BACKGROUND: In a given population the age pattern of mortality is an important determinant of total number of deaths, age structure, and through effects on age structure, the number of births and thereby growth. Good mortality models exist for most populations except those experiencing generalized HIV epidemics and some developing country populations. The large number of deaths concentrated at very young and adult ages in HIV-affected populations produce a unique 'humped' age pattern of mortality that is not reproduced by any existing mortality models. Both burden of disease reporting and population projection methods require age-specific mortality rates to estimate numbers of deaths and produce plausible age structures. For countries with generalized HIV epidemics these estimates should take into account the future trajectory of HIV prevalence and its effects on age-specific mortality. In this paper we present a parsimonious model of age-specific mortality for countries with generalized HIV/AIDS epidemics. METHODS AND FINDINGS: The model represents a vector of age-specific mortality rates as the weighted sum of three independent age-varying components. We derive the age-varying components from a Singular Value Decomposition of the matrix of age-specific mortality rate schedules. The weights are modeled as a function of HIV prevalence and one of three possible sets of inputs: life expectancy at birth, a measure of child mortality, or child mortality with a measure of adult mortality. We calibrate the model with 320 five-year life tables for each sex from the World Population Prospects 2010 revision that come from the 40 countries of the world that have and are experiencing a generalized HIV epidemic. Cross validation shows that the model is able to outperform several existing model life table systems. CONCLUSIONS: We present a flexible, parsimonious model of age-specific mortality for countries with generalized HIV epidemics. Combined with the outputs of existing epidemiological and demographic models, this model makes it possible to project future age-specific mortality profiles and number of deaths for countries with generalized HIV epidemics.

The INDEPTH standard population for low- and middle-income countries, 2013.

Crude rates such as the crude death rate are functions of both the age-specific rates and the age composition of a population. However, differences in the age structure between two populations or two time periods can result in specious differences in the corresponding crude rates making direct comparisons between populations or across time inappropriate. Therefore, when comparing crude rates between populations, it is desirable to eliminate or minimize the influence of age composition. This task is accomplished by using a standard age structure yielding an age-standardized rate. This paper proposes an updated International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) standard for use in low- and middle-income countries (LMICs) based on newly available data from the health and demographic surveillance system site members of the INDEPTH network located throughout Africa and southern Asia. The updated INDEPTH standard should better reflect the age structure of LMICs and result in more accurate health indicators and demographic rates. We demonstrate use of the new INDEPTH standard along with several existing 'world' standards and show how resulting age-standardized crude deaths rates differ when using the various standard age compositions.

The Age Pattern of Increases in Mortality Affected by HIV: Bayesian Fit of the Heligman-Pollard Model to Data from the Agincourt HDSS Field Site in Rural Northeast South Africa.

BACKGROUND: We investigate the sex-age-specific changes in the mortality of a prospectively monitored rural population in South Africa. We quantify changes in the age pattern of mortality in a parsimonious way by estimating the eight parameters of the Heligman-Pollard (HP) model of age-specific mortality. In its traditional form this model is difficult to fit and does not account for uncertainty. OBJECTIVE: 1. To quantify changes in the sex-age pattern of mortality experienced by a population with endemic HIV. 2. To develop and demonstrate a robust Bayesian estimation method for the HP model that accounts for uncertainty. METHODS: Bayesian estimation methods are adapted to work with the HP model. Temporal changes in parameter values are related to changes in HIV prevalence. RESULTS: Over the period when the HIV epidemic in South Africa was growing, mortality in the population described by our data increased profoundly with losses of life expectancy of ~15 years for both males and females. The temporal changes in the HP parameters reflect in a parsimonious way the changes in the age pattern of mortality. We develop a robust Bayesian method to estimate the eight parameters of the HP model and thoroughly demonstrate it. CONCLUSIONS: Changes in mortality in South Africa over the past fifteen years have been profound. The HP model can be fit well using Bayesian methods, and the results can be useful in developing a parsimonious description of changes in the age pattern of mortality. COMMENTS: The motivating aim of this work is to develop new methods that can be useful in applying the HP eight-parameter model of age-specific mortality. We have done this and chosen an interesting application to demonstrate the new methods.