A growing body of epigenetic research suggests that in-utero adaptations to environmental changes display important sex-specific variation. We test this heterogeneous adaptation hypothesis using data from 900 children born at the University Hospital in São Paulo, Brazil, between October 2013 and April 2014. Adjusted and unadjusted linear models were used to quantify the associations between prematurity, small for gestational age and children's physical and mental development at 12 months of age. Prematurity was negatively associated with neuropsychological development in fully adjusted models (z-score difference -0.42, 95% confidence intervals: -0.71, -0.14), but associations did not vary significantly by sex. For small for gestational age, associations with height-for-age, weight-for-age and neuropsychological development were also negative, but systematically larger for male than for female infants (p-values all <0.05). These results suggest that male fetuses may be more vulnerable to intra-uterine adversity than females; further research will be needed to better understand the mechanisms underlying these sex-specific associations.

BACKGROUND: The pathway from evidence generation to consumption contains many steps which can lead to overstatement or misinformation. The proliferation of internet-based health news may encourage selection of media and academic research articles that overstate strength of causal inference. We investigated the state of causal inference in health research as it appears at the end of the pathway, at the point of social media consumption. METHODS: We screened the NewsWhip Insights database for the most shared media articles on Facebook and Twitter reporting about peer-reviewed academic studies associating an exposure with a health outcome in 2015, extracting the 50 most-shared academic articles and media articles covering them. We designed and utilized a review tool to systematically assess and summarize studies' strength of causal inference, including generalizability, potential confounders, and methods used. These were then compared with the strength of causal language used to describe results in both academic and media articles. Two randomly assigned independent reviewers and one arbitrating reviewer from a pool of 21 reviewers assessed each article. RESULTS: We accepted the most shared 64 media articles pertaining to 50 academic articles for review, representing 68% of Facebook and 45% of Twitter shares in 2015. Thirty-four percent of academic studies and 48% of media articles used language that reviewers considered too strong for their strength of causal inference. Seventy percent of academic studies were considered low or very low strength of inference, with only 6% considered high or very high strength of causal inference. The most severe issues with academic studies' causal inference were reported to be omitted confounding variables and generalizability. Fifty-eight percent of media articles were found to have inaccurately reported the question, results, intervention, or population of the academic study. CONCLUSIONS: We find a large disparity between the strength of language as presented to the research consumer and the underlying strength of causal inference among the studies most widely shared on social media. However, because this sample was designed to be representative of the articles selected and shared on social media, it is unlikely to be representative of all academic and media work. More research is needed to determine how academic institutions, media organizations, and social network sharing patterns impact causal inference and language as received by the research consumer.

BACKGROUND: Differential trends in mortality suggest that stillbirths may dominate neonatal mortality in the medium to long run. Brazil has made major efforts to improve data collection on health indicators at granular geographic levels, and provides an ideal environment to test this hypothesis. Our goals were to examine levels and trends in stillbirths and neonatal deaths and the extent to which the mortality burden caused by stillbirths dominates neonatal mortality at the municipality- and state-level. METHODS: We used data from the Brazilian Ministry of Health's repository on births, fetal, and neonatal deaths (2010-2014) to calculate stillbirth and neonatal mortality rates for São Paulo state's 645 municipalities. RESULTS: At the state level, 7.9 per 1000 pregnancies ended in stillbirth (fetal death >22 weeks gestation or fetal weight >500g), but this varied from 0.0 to 28.4 per 1000 across municipalities. 7.9 per 1000 live births also died within the first 28 days. 42% of municipalities had a higher stillbirth rate than neonatal mortality rate, and in 61% of areas with low neonatal mortality (<8.0 per 1000), stillbirth rates exceeded neonatal mortality rates. CONCLUSIONS: This analysis suggests large variability and inequality in mortality outcomes at the sub-national level. The results also imply that stillbirth mortality may exceed neonatal mortality in Brazil and similar settings in the next few decades, which suggests a need for a shift in policy. This work further underscores the importance of continued research into causes and prevention of stillbirth.

BACKGROUND: Community health worker (CHW) programs are believed to be poorly coordinated, poorly integrated into national health systems, and lacking long-term support. Duplication of services, fragmentation, and resource limitations may have impeded the potential impact of CHWs for achieving HIV goals. This study assesses mediators of a more harmonized approach to implementing large-scale CHW programs for HIV in the context of complex health systems and multiple donors. METHODS AND FINDINGS: We undertook four country case studies in Lesotho, Mozambique, South Africa, and Swaziland between August 2015 and May 2016. We conducted 60 semistructured interviews with donors, government officials, and expert observers involved in CHW programs delivering HIV services. Interviews were triangulated with published literature, country reports, national health plans, and policies. Data were analyzed based on 3 priority areas of harmonization (coordination, integration, and sustainability) and 5 components of a conceptual framework (the health issue, intervention, stakeholders, health system, and context) to assess facilitators and barriers to harmonization of CHW programs. CHWs supporting HIV programs were found to be highly fragmented and poorly integrated into national health systems. Stakeholders generally supported increasing harmonization, although they recognized several challenges and disadvantages to harmonization. Key facilitators to harmonization included (i) a large existing national CHW program and recognition of nongovernmental CHW programs, (ii) use of common incentives and training processes for CHWs, (iii) existence of an organizational structure dedicated to community health initiatives, and (iv) involvement of community leaders in decision-making. Key barriers included a wide range of stakeholders and lack of ownership and accountability of non-governmental CHW programs. Limitations of our study include subjectively selected case studies, our focus on decision-makers, and limited generalizability beyond the countries analyzed. CONCLUSION: CHW programs for HIV in Southern Africa are fragmented, poorly integrated, and lack long-term support. We provide 5 policy recommendations to harmonize CHW programs in order to strengthen and sustain the role of CHWs in HIV service delivery.

BACKGROUND: Trends in food availability and metabolic risk factors in Brazil suggest a shift toward unhealthy dietary patterns and increased cardiometabolic disease risk, yet little is known about the impact of dietary and metabolic risk factors on cardiometabolic mortality in Brazil. METHODS: Based on data from Global Burden of Disease (GBD) Study, we used comparative risk assessment to estimate the burden of 11 dietary and 4 metabolic risk factors on mortality due to cardiovascular diseases and diabetes in Brazil in 2010. Information on national diets and metabolic risks were obtained from the Brazilian Household Budget Survey, the Food and Agriculture Organization database, and large observational studies including Brazilian adults. Relative risks for each risk factor were obtained from meta-analyses of randomized trials or prospective cohort studies; and disease-specific mortality from the GBD 2010 database. We quantified uncertainty using probabilistic simulation analyses, incorporating uncertainty in dietary and metabolic data and relative risks by age and sex. Robustness of findings was evaluated by sensitivity to varying feasible optimal levels of each risk factor. RESULTS: In 2010, high systolic blood pressure (SBP) and suboptimal diet were the largest contributors to cardiometabolic deaths in Brazil, responsible for 214,263 deaths (95% uncertainty interval [UI]: 195,073 to 233,936) and 202,949 deaths (95% UI: 194,322 to 211,747), respectively. Among individual dietary factors, low intakes of fruits and whole grains and high intakes of sodium were the largest contributors to cardiometabolic deaths. For premature cardiometabolic deaths (before age 70 years, representing 40% of cardiometabolic deaths), the leading risk factors were suboptimal diet (104,169 deaths; 95% UI: 99,964 to 108,002), high SBP (98,923 deaths; 95%UI: 92,912 to 104,609) and high body-mass index (BMI) (42,643 deaths; 95%UI: 40,161 to 45,111). CONCLUSION: suboptimal diet, high SBP, and high BMI are major causes of cardiometabolic death in Brazil, informing priorities for policy initiatives.

BACKGROUND: Saturated fat (SFA), ω-6 (n-6) polyunsaturated fat (PUFA), and trans fat (TFA) influence risk of coronary heart disease (CHD), but attributable CHD mortalities by country, age, sex, and time are unclear. METHODS AND RESULTS: National intakes of SFA, n-6 PUFA, and TFA were estimated using a Bayesian hierarchical model based on country-specific dietary surveys; food availability data; and, for TFA, industry reports on fats/oils and packaged foods. Etiologic effects of dietary fats on CHD mortality were derived from meta-analyses of prospective cohorts and CHD mortality rates from the 2010 Global Burden of Diseases study. Absolute and proportional attributable CHD mortality were computed using a comparative risk assessment framework. In 2010, nonoptimal intakes of n-6 PUFA, SFA, and TFA were estimated to result in 711 800 (95% uncertainty interval [UI] 680 700-745 000), 250 900 (95% UI 236 900-265 800), and 537 200 (95% UI 517 600-557 000) CHD deaths per year worldwide, accounting for 10.3% (95% UI 9.9%-10.6%), 3.6%, (95% UI 3.5%-3.6%) and 7.7% (95% UI 7.6%-7.9%) of global CHD mortality. Tropical oil-consuming countries were estimated to have the highest proportional n-6 PUFA- and SFA-attributable CHD mortality, whereas Egypt, Pakistan, and Canada were estimated to have the highest proportional TFA-attributable CHD mortality. From 1990 to 2010 globally, the estimated proportional CHD mortality decreased by 9% for insufficient n-6 PUFA and by 21% for higher SFA, whereas it increased by 4% for higher TFA, with the latter driven by increases in low- and middle-income countries. CONCLUSIONS: Nonoptimal intakes of n-6 PUFA, TFA, and SFA each contribute to significant estimated CHD mortality, with important heterogeneity across countries that informs nation-specific clinical, public health, and policy priorities.

BACKGROUND: Stunting affects one-third of children under 5 y old in developing countries, and 14% of childhood deaths are attributable to it. A large number of risk factors for stunting have been identified in epidemiological studies. However, the relative contribution of these risk factors to stunting has not been examined across countries. We estimated the number of stunting cases among children aged 24-35 mo (i.e., at the end of the 1,000 days' period of vulnerability) that are attributable to 18 risk factors in 137 developing countries. METHODS AND FINDINGS: We classified risk factors into five clusters: maternal nutrition and infection, teenage motherhood and short birth intervals, fetal growth restriction (FGR) and preterm birth, child nutrition and infection, and environmental factors. We combined published estimates and individual-level data from population-based surveys to derive risk factor prevalence in each country in 2010 and identified the most recent meta-analysis or conducted de novo reviews to derive effect sizes. We estimated the prevalence of stunting and the number of stunting cases that were attributable to each risk factor and cluster of risk factors by country and region. The leading risk worldwide was FGR, defined as being term and small for gestational age, and 10.8 million cases (95% CI 9.1 million-12.6 million) of stunting (out of 44.1 million) were attributable to it, followed by unimproved sanitation, with 7.2 million (95% CI 6.3 million-8.2 million), and diarrhea with 5.8 million (95% CI 2.4 million-9.2 million). FGR and preterm birth was the leading risk factor cluster in all regions. Environmental risks had the second largest estimated impact on stunting globally and in the South Asia, sub-Saharan Africa, and East Asia and Pacific regions, whereas child nutrition and infection was the second leading cluster of risk factors in other regions. Although extensive, our analysis is limited to risk factors for which effect sizes and country-level exposure data were available. The global nature of the study required approximations (e.g., using exposures estimated among women of reproductive age as a proxy for maternal exposures, or estimating the impact of risk factors on stunting through a mediator rather than directly on stunting). Finally, as is standard in global risk factor analyses, we used the effect size of risk factors on stunting from meta-analyses of epidemiological studies and assumed that proportional effects were fairly similar across countries. CONCLUSIONS: FGR and unimproved sanitation are the leading risk factors for stunting in developing countries. Reducing the burden of stunting requires a paradigm shift from interventions focusing solely on children and infants to those that reach mothers and families and improve their living environment and nutrition.

BACKGROUND: The growth of >300 million children <5 y old was mildly, moderately, or severely stunted worldwide in 2010. However, national estimates of the human capital and financial losses due to growth faltering in early childhood are not available. OBJECTIVE: We quantified the economic cost of growth faltering in developing countries. DESIGN: We combined the most recent country-level estimates of linear growth delays from the Nutrition Impact Model Study with estimates of returns to education in developing countries to estimate the impact of early-life growth faltering on educational attainment and future incomes. Primary outcomes were total years of educational attainment lost as well as the net present value of future wage earnings lost per child and birth cohort due to growth faltering in 137 developing countries. Bootstrapped standard errors were computed to account for uncertainty in modeling inputs. RESULTS: Our estimates suggest that early-life growth faltering in developing countries caused a total loss of 69.4 million y of educational attainment (95% CI: 41.7 million, 92.6 million y) per birth cohort. Educational attainment losses were largest in South Asia (27.6 million y; 95% CI: 20.0 million, 35.8 million y) as well as in Eastern (10.3 million y; 95% CI: 7.2 million, 12.9 million y) and Western sub-Saharan Africa (8.8 million y; 95% CI: 6.4 million, 11.5 million y). Globally, growth faltering in developing countries caused a total economic cost of $176.8 billion (95% CI: $100.9 billion, $262.6 billion)/birth cohort at nominal exchange rates, and $616.5 billion (95% CI: $365.3 billion, $898.9 billion) at purchasing power parity-adjusted exchange rates. At the regional level, economic costs were largest in South Asia ($46.6 billion; 95% CI: $33.3 billion, $61.1 billion), followed by Latin America ($44.7 billion; 95% CI: $19.2 billion, $74.6 billion) and sub-Saharan Africa ($34.2 billion; 95% CI: $24.4 billion, $45.3 billion). CONCLUSIONS: Our results indicate that the annual cost of early-childhood growth faltering is substantial. Further investment in scaling up effective interventions in this area is urgently needed and likely to yield long run benefits of $3 for every $1 invested.

BACKGROUND: Despite the availability of effective preventive measures, including intermittent preventive treatment for malaria during pregnancy (IPTp), malaria continues to cause substantial disease burden among pregnant women in malaria-endemic areas. IPTp coverage remains low, despite high antenatal care (ANC) attendance. To highlight areas of potential improvement, trends in IPTp coverage were assessed over time, missed opportunities to deliver IPTp at ANC were quantified, and delivery of IPTp was compared to that of tetanus toxoid (TT). METHODS: Data from 58 Demographic and Health Surveys conducted between 2003 and 2013 in 31 sub-Saharan African countries, with relevant questions on IPTp, ANC and TT were used to assess ANC attendance, and IPTp and TT delivery. A missed opportunity for IPTp delivery is an ANC visit at which IPTp could have been delivered according to policy but was not. RESULTS: The proportion of pregnant women who received ≥2 doses of IPTp increased in surveyed countries from nearly zero before to a median of 29.6% (IQR 20.1-42.5%) seven or more years after IPTp policy adoption. ANC attendance was high (median 76.6% reported ≥3 visits); however, even seven or more years post policy adoption, a median of 72.9% (IQR 58.4-79.5%) ANC visits were missed opportunities to deliver IPTp. Among primigravid women, a median of 61.5% (IQR 50.9-72.9%) received two doses of TT; delivery of recommended TT exceeded IPTp in all but one surveyed country. CONCLUSIONS: IPTp coverage measured by household surveys is unsatisfactorily low, even many years after policy adoption. The many missed opportunities to deliver IPTp suggest that deficiencies in delivery at ANC are a significant contributing factor to the low coverage levels. High levels of TT delivery indicate capacity to deliver preventive measures at ANC. Further research is required to determine the factors driving the discrepancies between IPTp and TT coverage, and how these may be addressed to improve IPTp coverage.

BACKGROUND: Sugar-sweetened beverages (SSBs) are consumed globally and contribute to adiposity. However, the worldwide impact of SSBs on burdens of adiposity-related cardiovascular diseases (CVDs), cancers, and diabetes mellitus has not been assessed by nation, age, and sex. METHODS AND RESULTS: We modeled global, regional, and national burdens of disease associated with SSB consumption by age/sex in 2010. Data on SSB consumption levels were pooled from national dietary surveys worldwide. The effects of SSB intake on body mass index and diabetes mellitus, and of elevated body mass index on CVD, diabetes mellitus, and cancers were derived from large prospective cohort pooling studies. Disease-specific mortality/morbidity data were obtained from Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We computed cause-specific population-attributable fractions for SSB consumption, which were multiplied by cause-specific mortality/morbidity to compute estimates of SSB-attributable death/disability. Analyses were done by country/age/sex; uncertainties of all input data were propagated into final estimates. Worldwide, the model estimated 184 000 (95% uncertainty interval, 161 000-208 000) deaths/y attributable to SSB consumption: 133 000 (126 000-139 000) from diabetes mellitus, 45 000 (26 000-61 000) from CVD, and 6450 (4300-8600) from cancers. Five percent of SSB-related deaths occurred in low-income, 70.9% in middle-income, and 24.1% in high-income countries. Proportional mortality attributable to SSBs ranged from <1% in Japanese >65 years if age to 30% in Mexicans <45 years of age. Among the 20 most populous countries, Mexico had largest absolute (405 deaths/million adults) and proportional (12.1%) deaths from SSBs. A total of 8.5 (2.8, 19.2) million disability-adjusted life years were related to SSB intake (4.5% of diabetes mellitus-related disability-adjusted life years). CONCLUSIONS: SSBs are a single, modifiable component of diet that can impact preventable death/disability in adults in high-, middle-, and low-income countries, indicating an urgent need for strong global prevention programs.

OBJECTIVE: To quantify global intakes of key foods related to non-communicable diseases in adults by region (n=21), country (n=187), age and sex, in 1990 and 2010. DESIGN: We searched and obtained individual-level intake data in 16 age/sex groups worldwide from 266 surveys across 113 countries. We combined these data with food balance sheets available in all nations and years. A hierarchical Bayesian model estimated mean food intake and associated uncertainty for each age-sex-country-year stratum, accounting for differences in intakes versus availability, survey methods and representativeness, and sampling and modelling uncertainty. SETTING/POPULATION: Global adult population, by age, sex, country and time. RESULTS: In 2010, global fruit intake was 81.3 g/day (95% uncertainty interval 78.9-83.7), with country-specific intakes ranging from 19.2-325.1 g/day; in only 2 countries (representing 0.4% of the world's population), mean intakes met recommended targets of ≥300 g/day. Country-specific vegetable intake ranged from 34.6-493.1 g/day (global mean=208.8 g/day); corresponding values for nuts/seeds were 0.2-152.7 g/day (8.9 g/day); for whole grains, 1.3-334.3 g/day (38.4 g/day); for seafood, 6.0-87.6 g/day (27.9 g/day); for red meats, 3.0-124.2 g/day (41.8 g/day); and for processed meats, 2.5-66.1 g/day (13.7 g/day). Mean national intakes met recommended targets in countries representing 0.4% of the global population for vegetables (≥400 g/day); 9.6% for nuts/seeds (≥4 (28.35 g) servings/week); 7.6% for whole grains (≥2.5 (50 g) servings/day); 4.4% for seafood (≥3.5 (100 g) servings/week); 20.3% for red meats (≤1 (100 g) serving/week); and 38.5% for processed meats (≤1 (50 g) serving/week). Intakes of healthful foods were generally higher and of less healthful foods generally lower at older ages. Intakes were generally similar by sex. Vegetable, seafood and processed meat intakes were stable over time; fruits, nuts/seeds and red meat, increased; and whole grains, decreased. CONCLUSIONS: These global dietary data by nation, age and sex identify key challenges and opportunities for optimising diets, informing policies and priorities for improving global health.

BACKGROUND: Sugar-sweetened beverages (SSBs), fruit juice, and milk are components of diet of major public health interest. To-date, assessment of their global distributions and health impacts has been limited by insufficient comparable and reliable data by country, age, and sex. OBJECTIVE: To quantify global, regional, and national levels of SSB, fruit juice, and milk intake by age and sex in adults over age 20 in 2010. METHODS: We identified, obtained, and assessed data on intakes of these beverages in adults, by age and sex, from 193 nationally- or subnationally-representative diet surveys worldwide, representing over half the world's population. We also extracted data relevant to milk, fruit juice, and SSB availability for 187 countries from annual food balance information collected by the United Nations Food and Agriculture Organization. We developed a hierarchical Bayesian model to account for measurement incomparability, study representativeness, and sampling and modeling uncertainty, and to combine and harmonize nationally representative dietary survey data and food availability data. RESULTS: In 2010, global average intakes were 0.58 (95%UI: 0.37, 0.89) 8 oz servings/day for SSBs, 0.16 (0.10, 0.26) for fruit juice, and 0.57 (0.39, 0.83) for milk. There was significant heterogeneity in consumption of each beverage by region and age. Intakes of SSB were highest in the Caribbean (1.9 servings/day; 1.2, 3.0); fruit juice consumption was highest in Australia and New Zealand (0.66; 0.35, 1.13); and milk intake was highest in Central Latin America and parts of Europe (1.06; 0.68, 1.59). Intakes of all three beverages were lowest in East Asia and Oceania. Globally and within regions, SSB consumption was highest in younger adults; fruit juice consumption showed little relation with age; and milk intakes were highest in older adults. CONCLUSIONS: Our analysis highlights the enormous spectrum of beverage intakes worldwide, by country, age, and sex. These data are valuable for highlighting gaps in dietary surveillance, determining the impacts of these beverages on global health, and targeting dietary policy.

BACKGROUND AND OBJECTIVE: The initial years of life are critical for physical growth and broader cognitive, motor, and socioemotional development, but the magnitude of the link between these processes remains unclear. Our objective was to produce quantitative estimates of the cross-sectional and prospective association of height-for-age z score (HAZ) with child development. METHODS: Observational studies conducted in low- and middle-income countries (LMICs) presenting data on the relationship of linear growth with any measure of child development among children <12 years of age were identified from a systematic search of PubMed, Embase, and PsycINFO. Two reviewers then extracted these data by using a standardized form. RESULTS: A total of 68 published studies conducted in 29 LMICs were included in the final database. The pooled adjusted standardized mean difference in cross-sectional cognitive ability per unit increase in HAZ for children ≤ 2 years old was +0.24 (95% confidence interval [CI], 0.14-0.33; I(2) = 53%) and +0.09 for children > 2 years old (95% CI, 0.05-0.12; I(2) = 78%). Prospectively, each unit increase in HAZ for children ≤ 2 years old was associated with a +0.22-SD increase in cognition at 5 to 11 years after multivariate adjustment (95% CI, 0.17-0.27; I(2) = 0%). HAZ was also significantly associated with earlier walking age and better motor scores (P < .05). CONCLUSIONS: Observational evidence suggests a robust positive association between linear growth during the first 2 years of life with cognitive and motor development. Effective interventions that reduce linear growth restriction may improve developmental outcomes; however, integration with environmental, educational, and stimulation interventions may produce larger positive effects.

OBJECTIVES: To quantify global consumption of key dietary fats and oils by country, age, and sex in 1990 and 2010. DESIGN: Data were identified, obtained, and assessed among adults in 16 age- and sex-specific groups from dietary surveys worldwide on saturated, omega 6, seafood omega 3, plant omega 3, and trans fats, and dietary cholesterol. We included 266 surveys in adults (83% nationally representative) comprising 1,630,069 unique individuals, representing 113 of 187 countries and 82% of the global population. A multilevel hierarchical Bayesian model accounted for differences in national and regional levels of missing data, measurement incomparability, study representativeness, and sampling and modelling uncertainty. SETTING AND POPULATION: Global adult population, by age, sex, country, and time. RESULTS: In 2010, global saturated fat consumption was 9.4%E (95%UI=9.2 to 9.5); country-specific intakes varied dramatically from 2.3 to 27.5%E; in 75 of 187 countries representing 61.8% of the world's adult population, the mean intake was <10%E. Country-specific omega 6 consumption ranged from 1.2 to 12.5%E (global mean=5.9%E); corresponding range was 0.2 to 6.5%E (1.4%E) for trans fat; 97 to 440 mg/day (228 mg/day) for dietary cholesterol; 5 to 3,886 mg/day (163 mg/day) for seafood omega 3; and <100 to 5,542 mg/day (1,371 mg/day) for plant omega 3. Countries representing 52.4% of the global population had national mean intakes for omega 6 fat ≥ 5%E; corresponding proportions meeting optimal intakes were 0.6% for trans fat (≤ 0.5%E); 87.6% for dietary cholesterol (<300 mg/day); 18.9% for seafood omega 3 fat (≥ 250 mg/day); and 43.9% for plant omega 3 fat (≥ 1,100 mg/day). Trans fat intakes were generally higher at younger ages; and dietary cholesterol and seafood omega 3 fats generally higher at older ages. Intakes were similar by sex. Between 1990 and 2010, global saturated fat, dietary cholesterol, and trans fat intakes remained stable, while omega 6, seafood omega 3, and plant omega 3 fat intakes each increased. CONCLUSIONS: These novel global data on dietary fats and oils identify dramatic diversity across nations and inform policies and priorities for improving global health.

BACKGROUND: High sodium intake increases blood pressure, a risk factor for cardiovascular disease, but the effects of sodium intake on global cardiovascular mortality are uncertain. METHODS: We collected data from surveys on sodium intake as determined by urinary excretion and diet in persons from 66 countries (accounting for 74.1% of adults throughout the world), and we used these data to quantify the global consumption of sodium according to age, sex, and country. The effects of sodium on blood pressure, according to age, race, and the presence or absence of hypertension, were calculated from data in a new meta-analysis of 107 randomized interventions, and the effects of blood pressure on cardiovascular mortality, according to age, were calculated from a meta-analysis of cohorts. Cause-specific mortality was derived from the Global Burden of Disease Study 2010. Using comparative risk assessment, we estimated the cardiovascular effects of current sodium intake, as compared with a reference intake of 2.0 g of sodium per day, according to age, sex, and country. RESULTS: In 2010, the estimated mean level of global sodium consumption was 3.95 g per day, and regional mean levels ranged from 2.18 to 5.51 g per day. Globally, 1.65 million annual deaths from cardiovascular causes (95% uncertainty interval [confidence interval], 1.10 million to 2.22 million) were attributed to sodium intake above the reference level; 61.9% of these deaths occurred in men and 38.1% occurred in women. These deaths accounted for nearly 1 of every 10 deaths from cardiovascular causes (9.5%). Four of every 5 deaths (84.3%) occurred in low- and middle-income countries, and 2 of every 5 deaths (40.4%) were premature (before 70 years of age). The rate of death from cardiovascular causes associated with sodium intake above the reference level was highest in the country of Georgia and lowest in Kenya. CONCLUSIONS: In this modeling study, 1.65 million deaths from cardiovascular causes that occurred in 2010 were attributed to sodium consumption above a reference level of 2.0 g per day. (Funded by the Bill and Melinda Gates Foundation.).

OBJECTIVES: To estimate global, regional (21 regions) and national (187 countries) sodium intakes in adults in 1990 and 2010. DESIGN: Bayesian hierarchical modelling using all identifiable primary sources. DATA SOURCES AND ELIGIBILITY: We searched and obtained published and unpublished data from 142 surveys of 24 h urinary sodium and 103 of dietary sodium conducted between 1980 and 2010 across 66 countries. Dietary estimates were converted to urine equivalents based on 79 pairs of dual measurements. MODELLING METHODS: Bayesian hierarchical modelling used survey data and their characteristics to estimate mean sodium intake, by sex, 5 years age group and associated uncertainty for persons aged 20+ in 187 countries in 1990 and 2010. Country-level covariates were national income/person and composition of food supplies. MAIN OUTCOME MEASURES: Mean sodium intake (g/day) as estimable by 24 h urine collections, without adjustment for non-urinary losses. RESULTS: In 2010, global mean sodium intake was 3.95 g/day (95% uncertainty interval: 3.89 to 4.01). This was nearly twice the WHO recommended limit of 2 g/day and equivalent to 10.06 (9.88-10.21) g/day of salt. Intake in men was ∼10% higher than in women; differences by age were small. Intakes were highest in East Asia, Central Asia and Eastern Europe (mean >4.2 g/day) and in Central Europe and Middle East/North Africa (3.9-4.2 g/day). Regional mean intakes in North America, Western Europe and Australia/New Zealand ranged from 3.4 to 3.8 g/day. Intakes were lower (<3.3 g/day), but more uncertain, in sub-Saharan Africa and Latin America. Between 1990 and 2010, modest, but uncertain, increases in sodium intakes were identified. CONCLUSIONS: Sodium intakes exceed the recommended levels in almost all countries with small differences by age and sex. Virtually all populations would benefit from sodium reduction, supported by enhanced surveillance.

BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: During the past decade, renewed global and national efforts to combat malaria have led to ambitious goals. We aimed to provide an accurate assessment of the levels and time trends in malaria mortality to aid assessment of progress towards these goals and the focusing of future efforts. METHODS: We systematically collected all available data for malaria mortality for the period 1980-2010, correcting for misclassification bias. We developed a range of predictive models, including ensemble models, to estimate malaria mortality with uncertainty by age, sex, country, and year. We used key predictors of malaria mortality such as Plasmodium falciparum parasite prevalence, first-line antimalarial drug resistance, and vector control. We used out-of-sample predictive validity to select the final model. FINDINGS: Global malaria deaths increased from 995,000 (95% uncertainty interval 711,000-1,412,000) in 1980 to a peak of 1,817,000 (1,430,000-2,366,000) in 2004, decreasing to 1,238,000 (929,000-1,685,000) in 2010. In Africa, malaria deaths increased from 493,000 (290,000-747,000) in 1980 to 1,613,000 (1,243,000-2,145,000) in 2004, decreasing by about 30% to 1,133,000 (848,000-1,591,000) in 2010. Outside of Africa, malaria deaths have steadily decreased from 502,000 (322,000-833,000) in 1980 to 104,000 (45,000-191,000) in 2010. We estimated more deaths in individuals aged 5 years or older than has been estimated in previous studies: 435,000 (307,000-658,000) deaths in Africa and 89,000 (33,000-177,000) deaths outside of Africa in 2010. INTERPRETATION: Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met. FUNDING: The Bill & Melinda Gates Foundation.

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.