Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Racial Inequities in Mortality Rate in Hospitalized Children.

BACKGROUND AND OBJECTIVES: Racial/ethnic inequities for inpatient mortality in children at a national level in the U.S. have not been explored. The objective of this study was to evaluate differences in inpatient mortality rate among different racial/ethnic groups, using the Kids' Inpatient Database. METHODS: A cross-sectional study of children of ages greater than 28 days and less than 21 years discharged during 2012 and 2016. Racial/ethnic groups - White, Black, Hispanic, Asian and Pacific Islander and Native Americans were analyzed in two cohorts, Cohort A (all discharges) and Cohort B (ventilated children). RESULTS: A total of 4,247,604 and 79,116 discharges were included in cohorts A and B, respectively. Univariate analysis showed that the inpatient mortality rate was highest among Asian and Pacific Islander children for both cohorts: A (0.47% [0.42-0.51]), B (10.9% [9.8-12.1]). Regression analysis showed that Asian and Pacific Islander and Black children had increased odds of inpatient mortality compared to White children: A (1.319 [1.162-1.496], 1.178 [1.105-1.257], respectively) and B (1.391 [1.199-1.613], 1.163 [1.079-1.255], respectively). Population-based hospital mortality was highest in Black children (1.17 per 10,000 children). CONCLUSIONS: Inpatient mortality rates are significantly higher in U.S. children of Asian and Pacific Islander and Black races compared to White children. U.S. population-based metrics such as hospitalization rate, ventilation rate, and hospital mortality rate are highest in Black children. Our data suggest that lower median household income alone may not account for a higher inpatient mortality rate. The causes and prevention of racial and ethnic inequities in hospitalized children need to be explored further.

The effects of cash transfers on adult and child mortality in low- and middle-income countries.

Poverty is an important social determinant of health that is associated with increased risk of death1-5. Cash transfer programmes provide non-contributory monetary transfers to individuals or households, with or without behavioural conditions such as children's school attendance6,7. Over recent decades, cash transfer programmes have emerged as central components of poverty reduction strategies of many governments in low- and middle-income countries6,7. The effects of these programmes on adult and child mortality rates remains an important gap in the literature, however, with existing evidence limited to a few specific conditional cash transfer programmes, primarily in Latin America8-14. Here we evaluated the effects of large-scale, government-led cash transfer programmes on all-cause adult and child mortality using individual-level longitudinal mortality datasets from many low- and middle-income countries. We found that cash transfer programmes were associated with significant reductions in mortality among children under five years of age and women. Secondary heterogeneity analyses suggested similar effects for conditional and unconditional programmes, and larger effects for programmes that covered a larger share of the population and provided larger transfer amounts, and in countries with lower health expenditures, lower baseline life expectancy, and higher perceived regulatory quality. Our findings support the use of anti-poverty programmes such as cash transfers, which many countries have introduced or expanded during the COVID-19 pandemic, to improve population health.

The New Crisis of Increasing All-Cause Mortality in US Children and Adolescents.

This Viewpoint discusses increased rates in pediatric mortality by age and cause between 1999 and 2021.

Estimated impact of the 2020 economic downturn on under-5 mortality for 129 countries.

In low- and middle-income countries (LMICs), economic downturns can lead to increased child mortality by affecting dietary, environmental, and care-seeking factors. This study estimates the potential loss of life in children under five years old attributable to economic downturns in 2020. We used a multi-level, mixed effects model to estimate the relationship between gross domestic product (GDP) per capita and under-5 mortality rates (U5MRs) specific to each of 129 LMICs. Public data were retrieved from the World Bank World Development Indicators database and the United Nations World Populations Prospects estimates for the years 1990-2020. Country-specific regression coefficients on the relationship between child mortality and GDP were used to estimate the impact on U5MR of reductions in GDP per capita of 5%, 10%, and 15%. A 5% reduction in GDP per capita in 2020 was estimated to cause an additional 282,996 deaths in children under 5 in 2020. At 10% and 15%, recessions led to higher losses of under-5 lives, increasing to 585,802 and 911,026 additional deaths, respectively. Nearly half of all the potential under-5 lives lost in LMICs were estimated to occur in Sub-Saharan Africa. Because most of these deaths will likely be due to nutrition and environmental factors amenable to intervention, countries should ensure continued investments in food supplementation, growth monitoring, and comprehensive primary health care to mitigate potential burdens.

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.

Child mortality in England during the COVID-19 pandemic.

OBJECTIVES: Using the National Child Mortality Database (NCMD), this work aims to investigate and quantify the characteristics of children dying of COVID-19, and to identify any changes in rate of childhood mortality during the pandemic. DESIGN: We compared the characteristics of the children who died in 2020, split by SARS-CoV-2 status. A negative binomial regression model was used to compare mortality rates in lockdown (23 March-28 June), with those children who died in the preceding period (6 January-22 March), as well as a comparable period in 2019. SETTING: England. PARTICIPANTS: Children (0-17 years). MAIN OUTCOME MEASURES: Characteristics and number of the children who died in 2020, split by SARS-CoV-2 status. RESULTS: 1550 deaths of children between 6th of January and 28 June 2020 were notified to the NCMD; 437 of the deaths were linked to SARS-CoV-2 virology records, 25 (5.7%) had a positive PCR result. PCR-positive children were less likely to be white (37.5% vs 69.4%, p=0.003) and were older (12.2 vs 0.7 years, p<0.0006) compared with child deaths without evidence of the virus. All-cause mortality rates were similar during lockdown compared with both the period before lockdown in 2020 (rate ratio (RR) 0.93 (0.84 to 1.02)) and a similar period in 2019 (RR 1.02 (0.92 to 1.13)). CONCLUSIONS: There is little to suggest that there has been excess mortality during the period of lockdown. The apparent higher frequency of SARS-CoV-2-positive tests among children from black, Asian and minority ethnic groups is consistent with findings in adults. Ongoing surveillance is essential as the pandemic continues.

Global, regional, and national causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the Sustainable Development Goals.

BACKGROUND: Causes of mortality are a crucial input for health systems for identifying appropriate interventions for child survival. We present an updated series of cause-specific mortality for neonates and children younger than 5 years from 2000 to 2019. METHODS: We updated cause-specific mortality estimates for neonates and children aged 1-59 months, stratified by level (low, moderate, or high) of mortality. We made a substantial change in the statistical methods used for previous estimates, transitioning to a Bayesian framework that includes a structure to account for unreported causes in verbal autopsy studies. We also used systematic covariate selection in the multinomial framework, gave more weight to nationally representative verbal autopsy studies using a random effects model, and included mortality due to tuberculosis. FINDINGS: In 2019, there were 5·30 million deaths (95% uncertainty range 4·92-5·68) among children younger than 5 years, primarily due to preterm birth complications (17·7%, 16·1-19·5), lower respiratory infections (13·9%, 12·0-15·1), intrapartum-related events (11·6%, 10·6-12·5), and diarrhoea (9·1%, 7·9-9·9), with 49·2% (47·3-51·9) due to infectious causes. Vaccine-preventable deaths, such as for lower respiratory infections, meningitis, and measles, constituted 21·7% (20·4-25·6) of under-5 deaths, and many other causes, such as diarrhoea, were preventable with low-cost interventions. Under-5 mortality has declined substantially since 2000, primarily because of a decrease in mortality due to lower respiratory infections, diarrhoea, preterm birth complications, intrapartum-related events, malaria, and measles. There is considerable variation in the extent and trends in cause-specific mortality across regions and for different strata of all-cause under-5 mortality. INTERPRETATION: Progress is needed to improve child health and end preventable deaths among children younger than 5 years. Countries should strategize how to reduce mortality among this age group using interventions that are relevant to their specific causes of death. FUNDING: Bill & Melinda Gates Foundation; WHO.

Características e tendência temporal das taxas de mortalidade de crianças e adolescentes em Mato Grosso e no Brasil, 2009 a 2020 / Características y tendencia temporal de la mortalidad en niños y adolescentes en Mato Grosso y Brasil, 2009 a 2020 / Characteristics and temporal trends of mortality rates in children and adolescents in Mato Grosso and Brazil, 2009-2020

Objetivo: analisar as características e a tendência temporal das taxas de mortalidade na população de 5 a 14 anos em Mato Grosso e no Brasil, no período de 2009 a 2020. Métodos: estudo ecológico de série temporal, sobre dados do Sistema de Informação sobre Mortalidade. As análises foram descritivas e de tendência, utilizando-se o modelo de regressão por pontos de inflexão (joinpoint) com cálculo da variação média no período (VMP). Resultados: no Brasil e em Mato Grosso, os óbitos foram predominantemente masculinos, evitáveis e por causas externas. Foi identificada tendência decrescente no Brasil (5 a 9 anos VMP: -2,9; IC95% -4,3;-1,6 e 10 a 14 anos VMP: -2,5; IC95% -3,3;-1,8) e estacionária em Mato Grosso (5 a 9 anos VMP: -2,0; IC95% -5,6;1,7 e 10 a 14 anos VMP: -0,1; IC95% -5,9;6,1). Conclusão: a tendência estável da mortalidade em patamares elevados demanda intervenções urgentes, visando a sua redução.

Objetivo: analizar las características y la tendencia temporal de las tasas de mortalidad en la población de 5 a 14 años en Mato Grosso y Brasil, desde 2009 hasta 2020. Métodos: estudio ecológico de serie temporal, sobre datos del Sistema de Información de Mortalidad. Se realizaron análisis descriptivos y de tendencia, utilizando el modelo de regresión por puntos de inflexión (joinpoint) y el cálculo de la variación media del periodo (VMP). Resultados: en Brasil y Mato Grosso, las muertes fueron predominantemente masculinas, evitables y por causas externas. Se identificó una tendencia decreciente en Brasil (5 a 9 años VPP: -2,9; IC95% -4,3;-1,6 y 10 a 14 años VMP: -2,5; IC95% -3,3;-1,8) y una tendencia estacionaria en Mato Grosso (5 a 9 años VMP: -2,0; IC95% -5,6;1,7 y 10 a 14 años VMP: -0,1; IC95% -5,9;6,1). Conclusión: la tendencia estacionaria de la mortalidad en niveles altos exige intervenciones urgentes orientadas a reducirla.

Objective: to analyze the characteristics and temporal trend of mortality rates in the population aged 5 to 14 years in Mato Grosso state and in Brazil, from 2009 to 2020. Methods: this was an ecological time-series study, based on data taken from the Mortality Information System. Descriptive and trend analyses were performed, using the joinpoint regression model and calculating the average annual percentage change (AAPC). Results: in Brazil and in Mato Grosso state, deaths were predominantly male, preventable and due to external causes. A falling trend was identified for Brazil (5-9 years AAPC: -2.9; 95%CI -4.3;-1.6 and 10-14 years AAPC: -2.5; 95%CI -3.3;-1.8), while a stationary trend was found in Mato Grosso (5-9 years AAPC: -2.0; 95%CI -5.6;1.7 and 10-14 years AAPC: -0.1; 95%CI -5.9;6.1). Conclusion: the stable trend of mortality at high levels demands urgent interventions to reduce it.

Estimation of health impact from digitalizing last-mile Logistics Management Information Systems (LMIS) in Ethiopia, Tanzania, and Mozambique: A Lives Saved Tool (LiST) model analysis.

BACKGROUND: Digital health has become a widely recognized approach to addressing a range of health needs, including advancing universal health coverage and achieving the Sustainable Development Goals. At present there is limited evidence on the impact of digital interventions on health outcomes. A growing body of peer-reviewed evidence on digitalizing last-mile electronic logistics management information systems (LMIS) presents an opportunity to estimate health impact. METHODS: The impact of LMIS on reductions in stockouts was estimated from primary data and peer-reviewed literature, with three scenarios of impact: 5% stockout reduction (conservative), 10% stockout reduction (base), and 15% stockout reduction (optimistic). Stockout reduction data was inverted to stock availability and improved coverage for vaccines and essential medicines using a 1:1 conversion factor. The Lives Saved Tool (LiST) model was used to estimate health impact from lives saved in newborns and children in Mozambique, Tanzania, and Ethiopia between 2022 and 2026 across the three scenarios. RESULTS: Improving coverage of vaccines with a digital LMIS intervention in the base scenario (conservative, optimistic) could prevent 4,924 (2,578-6,094), 3,998 (1,621-4,915), and 17,648 (12,656-22,776) deaths in Mozambique, Tanzania, and Ethiopia, respectively over the forecast timeframe. In addition, scaling up coverage of non-vaccine medications could prevent 17,044 (8,561-25,392), 21,772 (10,976-32,401), and 34,981 (17,543-52,194) deaths in Mozambique, Tanzania, and Ethiopia, respectively. In the base model scenario, the maximum percent reduction in deaths across all geographies was 1.6% for vaccines and 4.1% for non-vaccine medications. INTERPRETATION: This study projects that digitalization of last-mile LMIS would reduce child mortality by improving coverage of lifesaving health commodities. This analysis helps to build the evidence base around the benefits of deploying digital solutions to address health challenges. Findings should be interpreted carefully as stockout reduction estimates are derived from a small number of studies.

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

Decreasing death rates and causes of death in Icelandic children-A longitudinal analysis.

BACKGROUND: Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century. METHODS: The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear. FINDINGS: Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant. INTERPRETATION: Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide.

Azithromycin for the prevention of rehospitalisation and death among Kenyan children being discharged from hospital: a double-blind, placebo-controlled, randomised controlled trial.

BACKGROUND: Mass drug administration of azithromycin to children in sub-Saharan Africa has been shown to improve survival in high-mortality settings. The period after hospital discharge is a time of elevated risk unaddressed by current interventions and might provide an opportunity for targeting empirical azithromycin administration. We aimed to assess the efficacy of azithromycin administered at hospital discharge on risk of death and rehospitalisation in Kenyan children younger than 5 years. METHODS: In this double-blind, placebo-controlled randomised trial, children were randomly assigned (1:1) to receive a 5-day course of azithromycin (oral suspension 10 mg/kg on day 1, followed by 5mg/kg per day on days 2-5) or identically appearing and tasting placebo at discharge from four hospitals in western Kenya. Children were eligible if they were aged 1-59 months at hospital discharge, weighed at least 2 kg, and had been admitted to hospital for any medical reason other than trauma, poisoning, or congenital anomaly. The primary outcome was death or rehospitalisation in the subsequent 6-month period in a modified intention-to-treat population, compared by randomisation group with Cox proportional hazards regression and Kaplan-Meier. Azithromycin resistance in Escherichia coli isolates from a random subset of children was compared by randomisation group with generalised estimating equations. This trial is registered with ClinicalTrials.gov, NCT02414399. FINDINGS: Between June 28, 2016, and Nov 4, 2019, 1400 children were enrolled in the trial at discharge from hospital, with 703 (50·2%) randomly assigned to azithromycin and 697 (49·8%) to placebo. Among the 1398 children included in the modified intention-to-treat analysis (702 in the azithromycin group and 696 in the placebo group), the incidence of death or rehospitalisation was 20·4 per 100 child-years in the azithromycin group and 22·5 per 100 child-years in the placebo group (adjusted hazard ratio 0·91, 95·5% CI 0·64-1·29, p=0·58). Azithromycin resistance was common in commensal E coli isolates from enrolled children before randomisation (37·7% of 406 isolates) despite only 3·7% of children having received a macrolide antibiotic during the hospitalisation. Azithromycin resistance was slightly higher at 3 months after randomisation in the azithromycin group (26·9%) than in the placebo group (19·1%; adjusted prevalence ratio 1·41, 95% CI 0·95-2·09, p=0·088), with no difference observed at 6 months (1·17, 0·78-1·76, p=0·44). INTERPRETATION: We did not observe a significant benefit of a 5-day course of azithromycin delivered to children younger than 5 years at hospital discharge despite the overall high risk of mortality and rehospitalisation. These findings highlight the need for more research into mechanisms and interventions for prevention of morbidity and mortality in the post-discharge period. FUNDING: Eunice Kennedy Shriver National Institute of Child Health & Human Development.

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019.

BACKGROUND: Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. METHODS: We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. FINDINGS: Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3-74·0) in 2000 to 37·1 (33·2-41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8-29·5) in 2000 to 17·9 (16·3-19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05-10·30) in 2000 and 5·05 million (4·27-6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53-4·02]) in 2000 to 48% (2·42 million; 2·06-2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71-0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27-1·58) deaths per 1000 livebirths, and in 2019, there were as many as 1·87 million (95% UI 1·35-2·58; 37% [95% UI 32-43]) of 5·05 million more deaths of children younger than 5 years than the survival potential frontier. INTERPRETATION: Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. FUNDING: Bill & Melinda Gates Foundation.

Effect of health systems context on infant and child mortality in sub-Saharan Africa from 1995 to 2015, a longitudinal cohort analysis.

Each year, > 3 million children die in sub-Saharan Africa before their fifth birthday. Most deaths are preventable or avoidable through interventions delivered in the primary healthcare system. However, evidence regarding the impact of health system characteristics on child survival is sparse. We assembled a retrospective cohort of > 250,000 children in seven countries in sub-Saharan Africa. We described their health service context at the subnational level using standardized surveys and employed parametric survival models to estimate the effect of three major domains of health services-quality, access, and cost-on infant and child survival, after adjusting for child, maternal, and household characteristics. Between 1995 and 2015 we observed 13,629 deaths in infants and 5149 in children. In fully-adjusted models, the largest effect sizes were related to fees for services. Immunization fees were correlated with poor child survival (HR = 1.20, 95% CI 1.12-1.28) while delivery fees were correlated with poor infant survival (HR = 1.11, 95% CI 1.01-1.21). Accessibility of facilities and greater concentrations of private facilities were associated with improved infant and child survival. The proportion of facilities with a doctor was correlated with increased risk of death in children and infants. We quantify the impact of health service environment on survival up to five years of age. Reducing health care costs and improving the accessibility of health facilities should remain a priority for improving infant and child survival. In the absence of these fundamental investments, more specialized interventions may not achieve their desired impact.

Parental education and inequalities in child mortality: a global systematic review and meta-analysis.

BACKGROUND: The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals. METHODS: This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data. The literature search of seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science) was done between Jan 23 and Feb 8, 2019, and updated on Jan 7, 2021, with no language or publication date restrictions. Teams of independent reviewers assessed each record for its inclusion of individual-level data on parental education and child mortality and excluded articles on the basis of study design and availability of relevant statistics. Full-text screening was done in 15 languages. Data extracted from these studies were combined with primary microdata from the DHS for meta-analyses relating maternal or paternal education with mortality at six age intervals: 0-27 days, 1-11 months, 1-4 years, 0-4 years, 0-11 months, and 1 month to 4 years. Novel mixed-effects meta-regression models were implemented to address heterogeneity in referent and exposure measures among the studies and to adjust for study-level covariates (wealth or income, partner's years of schooling, and sex of the child). This study was registered with PROSPERO (CRD42020141731). FINDINGS: The systematic review returned 5339 unique records, yielding 186 included studies after exclusions. DHS data were compiled from 114 unique surveys, capturing 3 112 474 livebirths. Data extracted from the systematic review were synthesized together with primary DHS data, for meta-analysis on a total of 300 studies from 92 countries. Both increased maternal and paternal education showed a dose-response relationship linked to reduced under-5 mortality, with maternal education emerging as a stronger predictor. We observed a reduction in under-5 mortality of 31·0% (95% CI 29·0-32·6) for children born to mothers with 12 years of education (ie, completed secondary education) and 17·3% (15·0-18·8) for children born to fathers with 12 years of education, compared with those born to a parent with no education. We also showed that a single additional year of schooling was, on average, associated with a reduction in under-5 mortality of 3·04% (2·82-3·23) for maternal education and 1·57% (1·35-1·72) for paternal education. The association between higher parental education and lower child mortality was significant for both parents at all ages studied and was largest after the first month of life. The meta-analysis framework incorporated uncertainty associated with each individual effect size into the model fitting process, in an effort to decrease the risk of bias introduced by study design and quality. INTERPRETATION: To our knowledge, this study is the first effort to systematically quantify the transgenerational importance of education for child survival at the global level. The results showed that lower maternal and paternal education are both risk factors for child mortality, even after controlling for other markers of family socioeconomic status. This study provides robust evidence for universal quality education as a mechanism to achieve the Sustainable Development Goal target 3.2 of reducing neonatal and child mortality. FUNDING: Research Council of Norway, Bill & Melinda Gates Foundation, and Rockefeller Foundation-Boston University Commission on Social Determinants, Data, and Decision Making (3-D Commission).