SummaryBackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.MethodsWe estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting.FindingsGlobally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 mil...

Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. MethodsGBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each agesex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobac...

SummaryBackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations.MethodsWe used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.FindingsIn 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). I...

Summary Background Although gains in newborn survival have been achieved in many low-income and middle-income countries, reductions in stillbirth and neonatal mortality have been slow. Prematurity complications are a major driver of stillbirth and neonatal mortality. We aimed to assess the effect of a quality improvement package for intrapartum and immediate newborn care on stillbirth and preterm neonatal survival in Kenya and Uganda, where evidence-based practices are often underutilised. Methods This unblinded cluster-randomised controlled trial was done in western Kenya and eastern Uganda at facilities that provide 24-h maternity care with at least 200 births per year. The study assessed outcomes of low-birthweight and preterm babies. Eligible facilities were pair-matched and randomly assigned (1:1) into either the intervention group or the control group. All facilities received maternity register data strengthening and a modified WHO Safe Childbirth Checklist; facilities in the intervention group additionally received provider mentoring using PRONTO simulation and team training as well as quality improvement collaboratives. Liveborn or fresh stillborn babies who weighed between 1000 g and 2500 g, or less than 3000 g with a recorded gestational age of less than 37 weeks, were included in the analysis. We abstracted data from maternity registers for maternal and birth outcomes. Follow-up was done by phone or in person to identify the status of the infant at 28 days. The primary outcome was fresh stillbirth and 28-day neonatal mortality. This trial is registered with ClinicalTrials.gov , NCT03112018 . Findings Between Oct 1, 2016, and April 30, 2019, 20 facilities were randomly assigned to either the intervention group (n=10) or the control group (n=10). Among 5343 eligible babies in these facilities, we assessed outcomes of 2938 newborn and fresh stillborn babies (1447 in the intervention and 1491 in the control group). 347 (23%) of 1491 infants in the control group were stillborn or died in the neonatal period compared with 221 (15%) of 1447 infants in the intervention group at 28 days (odds ratio 0·66, 95% CI 0·54–0·81). No harm or adverse effects were found. Interpretation Fresh stillbirth and neonatal mortality among low-birthweight and preterm babies can be decreased using a package of interventions that reinforces evidence-based practices and invests in health system strengthening. Funding Bill & Melinda Gates Foundation.

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BackgroundToxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month.MethodsCord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+), B lymphocytes (CD19+) and natural killer (NK) cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH) and particulate matter < 2.5 micrometer in diameter (PM2.5) were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births.ResultsThe adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation.ConclusionsPAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.

BackgroundInadequately treated, preeclampsia and eclampsia (PE/E) may rapidly lead to severe complications in both mothers and neonates, and are estimated to cause 60,000 global maternal deaths annually. Simulation-based training on obstetric and neonatal emergency management has demonstrated promising results in low- and middle-income countries. However, the impact of simulation training on use of evidence-based practices for PE/E diagnosis and management in low-resource settings remains unknown.MethodsThis study was based on a statewide, high fidelity in-situ simulation training program developed by PRONTO International and implemented in collaboration with CARE India on PE/E management in Bihar, India. Using a mixed methods approach, we evaluated changes over time in nurse mentees’ use of evidence-based practices during simulated births at primary health clinics. We compared the proportion and efficiency of evidence-based practices completed during nurse mentees’ first and last participation in simulated PE/E cases. Twelve semi-structured interviews with nurse mentors explored barriers and enablers to high quality PE/E care in Bihar.ResultsA total of 39 matched first and last simulation videos, paired by facility, were analyzed. Videos occurred a median of 62 days apart and included 94 nurses from 33 primary health centers. Results showed significant increases in the median number of ‘key history questions asked,’ (1.0 to 2.0, p = 0.03) and ‘key management steps completed,’ (2.0 to 3.0, p = 0.03). The time from BP measured to magnesium sulfate given trended downwards by 3.2 min, though not significantly (p = 0.06). Key barriers to high quality PE/E care included knowledge gaps, resource shortages, staff hierarchy between physicians and nurses, and poor relationships with patients. Enablers included case-based and simulation learning, promotion of teamwork and communication, and effective leadership.ConclusionSimulation training improved the use of evidence-based practices in PE/E simulated cases and has the potential to increase nurse competency in diagnosing and managing complex maternal complications such as PE/E. However, knowledge gaps, resource limitations, and interpersonal barriers must be addressed in order to improve care. Teamwork, communication, and leadership are key mechanisms to facilitate high quality PE/E care in Bihar.

BackgroundBirthweight and gestational age are associated with socioeconomic deprivation, but the evidence in relation to temporal changes in these associations is sparse. We investigated changes in the associations between socioeconomic status (SES) and birthweight and gestational age in Newcastle upon Tyne, North of England, during 1961–2000.MethodsWe used population-based data from hospital neonatal records on all singleton births to mothers resident in Newcastle (births with complete covariate information n = 113,182). We used linear regression to analyse the associations between neighbourhood SES and birthweight over the entire 40-year period and by decade, and logistic regression for associations with low birthweight (LBW) and preterm birth, adjusting for potential confounders.ResultsThere was a significant interaction between SES and decade of birth for birthweight (p = 0.028) and preterm birth (p < 0.001). Socioeconomic gradients were similar in each decade for birthweight outcomes, but for preterm birth, socioeconomic disparities were more evident in the later decades [for 1961–70, odds ratio (OR) was 1.1, 95% CI 0.9, 1.3, for the most deprived versus the least deprived quartile, while for 1991–2000, the corresponding OR was 1.5, 95% CI 1.3, 1.7]. In each decade, there was a significant decrease in birthweight adjusted for gestational age for the most deprived compared to the least deprived SES group [1961–1970: –113.4 g (95% CI–133.0, –93.8); 1991–2000: –97.5 g (95% CI–113.0, –82.0)], while there was a significant increase in birthweight in each SES group over time.ConclusionsSocioeconomic inequalities did not narrow over the four decades for birthweight and widened for preterm birth. Mean birthweight adjusted for gestational age increased in all socioeconomic groups, suggesting an overall increase in fetal growth.