Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma.

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts.

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

Recent changes in growth trajectories: a population-based cohort study of over 5 million Brazilian children born between 2001 and 2014.

Background: There is limited evidence on recent trends in childhood growth trajectories in Low-/middle-income countries. We investigated how age-trajectories for height and Body Mass Index (BMI) have changed among Brazilian children born in two different time periods after 2000. Methods: We used a population-based cohort (part of the "Cohort of 100-Million Brazilians") created by the linkage of three Brazilian administrative databases: the Cadastro Único of the Federal Government, the National System of Live Births and the National Nutritional and Food Surveillance System. We included longitudinal data on 5,750,214 children who were 3 to <10 years of age and born between 2001 and 2014 (20,209,133 observations). We applied fractional polynomial models with random-effects to estimate mean height and BMI trajectories for children. Findings: Compared to children born in 2001-2007, the cohort born in 2008-2014 were on average taller, by a z-score of 0.15 in boys and 0.12 in girls. Their height trajectories shifted upwards, by approximately 1 cm in both sexes. Levels of BMI increased little, by a z-score of 0.06 (boys) and 0.04 (girls). Mean BMI trajectories also changed little. However, the prevalence of overweight/obesity increased between cohorts, e.g., from 26.8% to 30% in boys and 23.9%-26.6% in girls aged between 5 and <10 years. Interpretation: An increase of 1 cm in mean height of Brazilian children during a short period indicates the improvement in maternal and child health, especially those from low-income families due to the new health and welfare policies in Brazil. Although mean BMI changed little, the prevalence of child overweight/obesity slightly increased and remained high. Funding: This work was supported by National Council for Scientific and Technological Development - CNPq; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre; Society for the Study of Human Biology; Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG; Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Complexo da Saúde do Ministério da Saúde - Decit/SECTICS/MS. The study also used resources from the Centre for Data and Knowledge Integration for Health (CIDACS), which receives funding from the Bill & Melinda Gates Foundation, the Wellcome Trust, the Health Surveillance Secretariat of the Ministry of Health and the Secretariat of Science and Technology of the State of Bahia (SECTI-BA).

The rising trends of self-harm in Brazil: an ecological analysis of notifications, hospitalisations, and mortality between 2011 and 2022.

Background: Self-harm is considered an important public health issue and is comprised by a wide range of definitions and behaviours. It is estimated that suicide affects more than 700,000 individuals every year, although, globally, there is a lack of evidence on other self-harm behaviour, such as attempted suicide. The objective of this study is to report and examine temporal trends of notifications, hospitalisations related to self-harm and suicide rates in Brazil between 2011 and 2022, as well as investigating differences in sociodemographic characteristics, methods, and region. Methods: This ecological study used secondary, Brazilian Health Information System data between 2011 and 2022. Self-harm notifications were collected from the Notifiable Diseases Information System (SINAN); self-harm hospitalisations from the Hospital Information System (SIH), and suicide data from the Mortality Information System (SIM). We calculated self-harm notifications, hospitalisations, and suicide rates by sex, age, race, region, and overall. We assessed time-related trends using Joinpoint regression analyses. Findings: From 2011 to 2022, 720,480 self-harm notifications, 104,458 self-harm hospitalisations, and 147,698 suicides were recorded in Brazil. In this period, self-harm notifications (AAPC: 21.13 (CI: 17.50, 25.33)) and suicide (AAPC: 3.70 (CI: 3.05, 4.38)) have increased in the country. Male adults (25-59 years old) and the elderly (>60 years old) continue to be the groups most affected by suicide, with respective rates of 9.59 and 8.60/100,000 in 2022. However, the largest percentage increases have been seen in young people (AAPC: 6.14 (CI: 4.57, 7.88)). The Indigenous population had the highest self-harm notification (103.72, 10,000) and suicide (16.58/100,000) rates, but the lowest hospitalisation rates (1.14/100,000) in 2022), compared to the overall population (70.06, 7.27, and 4.69/100,000, respectively, in 2022). Interpretation: The observed trend of increased self-harm notifications and suicide rates suggests the need for a greater allocation of resources to strategies to prevent self-harm and suicide. The Indigenous population seems to be the group with less access to healthcare. Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number R01MH128911-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Evaluating the relationship between conditional cash transfer programme on preterm births: a retrospective longitudinal study using the 100 million Brazilian cohort.

BACKGROUND: Preterm births increase mortality and morbidity during childhood and later life, which is closely associated with poverty and the quality of prenatal care. Therefore, income redistribution and poverty reduction initiatives may be valuable in preventing this outcome. We assessed whether receipt of the Brazilian conditional cash transfer programme - Bolsa Familia Programme, the largest in the world - reduces the occurrence of preterm births, including their severity categories, and explored how this association differs according to prenatal care and the quality of Bolsa Familia Programme management. METHODS: A retrospective cohort study was performed involving the first live singleton births to mothersenrolled in the 100 Million Brazilian Cohort from 2004 to 2015, who had at least one child before cohort enrollment. Only the first birth during the cohort period was included, but born from 2012 onward. A deterministic linkage with the Bolsa Familia Programme payroll dataset and a similarity linkage with the Brazilian Live Birth Information System were performed. The exposed group consisted of newborns to mothers who received Bolsa Familia from conception to delivery. Our outcomes were infants born with a gestational age < 37 weeks: (i) all preterm births, (ii) moderate-to-late (32-36), (iii) severe (28-31), and (iv) extreme (< 28) preterm births compared to at-term newborns. We combined propensity score-based methods and weighted logistic regressions to compare newborns to mothers who did and did not receive Bolsa Familia, controlling for socioeconomic conditions. We also estimated these effects separately, according to the adequacy of prenatal care and the index of quality of Bolsa Familia Programme management. RESULTS: 1,031,053 infants were analyzed; 65.9% of the mothers were beneficiaries. Bolsa Familia Programme was not associated with all sets of preterm births, moderate-to-late, and severe preterm births, but was associated with a reduction in extreme preterm births (weighted OR: 0.69; 95%CI: 0.63-0.76). This reduction can also be observed among mothers receiving adequate prenatal care (weighted OR: 0.66; 95%CI: 0.59-0.74) and living in better Bolsa Familia management municipalities (weighted OR: 0.56; 95%CI: 0.43-0.74). CONCLUSIONS: An income transfer programme for pregnant women of low-socioeconomic status, conditional to attending prenatal care appointments, has been associated with a reduction in extremely preterm births. These programmes could be essential in achieving Sustainable Development Goals.

Identifying biologically implausible values in big longitudinal data: an example applied to child growth data from the Brazilian food and nutrition surveillance system.

BACKGROUND: Several strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data. METHODS: Length/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The following cutoffs for residuals were tested to flag those: -3/+3, -4/+4, -5/+5, -6/+6. The selected child growth indicators included length/height-for-age z-scores and weight-for-age z-scores, classified according to the WHO charts. RESULTS: The dataset included 50,154,738 records from 10,775,496 children. Boys and girls had 5.74% and 5.31% of length/height and 5.19% and 4.74% of weight values flagged as population outliers, respectively. After removing those, the percentage of longitudinal outliers varied from 0.02% (<-6/>+6) to 1.47% (<-3/>+3) for length/height and from 0.07 to 1.44% for weight in boys. In girls, the percentage of longitudinal outliers varied from 0.01 to 1.50% for length/height and from 0.08 to 1.45% for weight. The initial removal of population outliers played the most substantial role in the growth trajectories as it was the first step in the cleaning process, while the additional removal of longitudinal outliers had lower influence on those, regardless of the cutoff adopted. The prevalence of the selected indicators were also affected by both population and longitudinal (to a lesser extent) outliers. CONCLUSIONS: Although both population and longitudinal outliers can detect biologically implausible values in child growth data, removing population outliers seemed more relevant in this large administrative dataset, especially in calculating summary statistics. However, both types of outliers need to be identified and removed for the proper evaluation of trajectories.

Association of interpregnancy interval with adverse pregnancy outcomes according to the outcomes of the preceding pregnancy: a longitudinal study with 4.7 million live births from Brazil.

Background: Earlier studies have proposed a link between the Interpregnancy Interval (IPI) and unfavorable birth outcomes. However, it remains unclear if the outcomes of previous births could affect this relationship. We aimed to investigate whether the occurrence of adverse outcomes-small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW)-at the immediately preceding pregnancy could alter the association between IPI and the same outcomes at the subsequent pregnancy. Methods: We used a population-based linked cohort from Brazil (2001-2015). IPI was measured as the difference, in months, between the preceding birth and subsequent conception. Outcomes included SGA (<10th birthweight percentile for gestational age and sex), LBW (<2500 g), and PTB (gestational age <37 weeks). We calculated risk ratios (RRs), using the IPI of 18-22 months as the reference IPI category, we also stratified by the number of adverse birth outcomes at the preceding pregnancy. Findings: Among 4,788,279 births from 3,804,152 mothers, absolute risks for subsequent SGA, PTB, and LBW were higher for women with more adverse outcomes in the preceding delivery. The RR of SGA and LBW for IPIs <6 months were greater for women without previous adverse outcomes (SGA: 1.44 [95% Confidence Interval (CI): 1.41-1.46]; LBW: 1.49 [1.45-1.52]) compared to those with three previous adverse outcomes (SGA: 1.20 [1.10-1.29]; LBW: 1.24 [1.15-1.33]). IPIs ≥120 months were associated with greater increases in risk for LBW and PTB among women without previous birth outcomes (LBW: 1.59; [1.53-1.65]; PTB: 2.45 [2.39-2.52]) compared to women with three adverse outcomes at the index birth (LBW: 0.92 [0.78-1.06]; PTB: 1.66 [1.44-1.88]). Interpretation: Our study suggests that women with prior adverse outcomes may have higher risks for adverse birth outcomes in subsequent pregnancies. However, risk changes due to differences in IPI length seem to have a lesser impact compared to women without a prior event. Considering maternal obstetric history is essential in birth spacing counseling. Funding: Wellcome Trust225925/Z/22/Z.

Risk of death following chikungunya virus disease in the 100 Million Brazilian Cohort, 2015-18: a matched cohort study and self-controlled case series.

BACKGROUND: Chikungunya virus outbreaks have been associated with excess deaths at the ecological level. Previous studies have assessed the risk factors for severe versus mild chikungunya virus disease. However, the risk of death following chikungunya virus disease compared with the risk of death in individuals without the disease remains unexplored. We aimed to investigate the risk of death in the 2 years following chikungunya virus disease. METHODS: We used a population-based cohort study and a self-controlled case series to estimate mortality risks associated with chikungunya virus disease between Jan 1, 2015, and Dec 31, 2018, in Brazil. The dataset was created by linking national databases for social programmes, notifiable diseases, and mortality. For the matched cohort design, individuals with chikungunya virus disease recorded between Jan 1, 2015, and Dec 31, 2018, were considered as exposed and those who were arbovirus disease-free and alive during the study period were considered as unexposed. For the self-controlled case series, we included all deaths from individuals with a chikungunya virus disease record, and each individual acted as their own control according to different study periods relative to the date of disease. The primary outcome was all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischaemic heart diseases, diabetes, and cerebrovascular diseases. FINDINGS: In the matched cohort study, we included 143 787 individuals with chikungunya virus disease who were matched, at the day of symptom onset, to unexposed individuals using sociodemographic factors. The incidence rate ratio (IRR) of death within 7 days of chikungunya symptom onset was 8·40 (95% CI 4·83-20·09) as compared with the unexposed group and decreased to 2·26 (1·50-3·77) at 57-84 days and 1·05 (0·82-1·35) at 85-168 days, with IRR close to 1 and wide CI in the subsequent periods. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58-7·00) for cerebrovascular diseases, 3·75 (1·33-17·00) for diabetes, and 3·67 (1·25-14·00) for ischaemic heart disease, and there was no evidence of increased risk in the subsequent periods. For the self-controlled case series study, 1933 individuals died after having had chikungunya virus disease and were included in the analysis. The IRR of all-cause natural death within 7 days of symptom onset of chikungunya virus disease was 8·75 (7·18-10·66) and decreased to 1·59 (1·26-2·00) at 57-84 days and 1·09 (0·92-1·29) at 85-168 days. For the secondary outcomes, the IRRs of deaths within 28 days after disease onset were: 2·73 (1·50-4·96) for cerebrovascular diseases, 8·43 (5·00-14·21) for diabetes, and 2·38 (1·33-4·26) for ischaemic heart disease, and there was no evidence of increased risk at 85-168 days. INTERPRETATION: Chikungunya virus disease is associated with an increased risk of death for up to 84 days after symptom onset, including deaths from cerebrovascular diseases, ischaemic heart diseases, and diabetes. This study highlights the need for equitable access to approved vaccines and effective anti-chikungunya virus therapeutics and reinforces the importance of robust vector-control efforts to reduce viral transmission. FUNDING: Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia, Wellcome Trust, and UK Medical Research Council. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Income determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians.

Living with extremely low-income is an important risk factor for HIV/AIDS and can be mitigated by conditional cash transfers. Using a cohort of 22.7 million low-income individuals during 9 years, we evaluated the effects of the world's largest conditional cash transfer, the Programa Bolsa Família, on HIV/AIDS-related outcomes. Exposure to Programa Bolsa Família was associated with reduced AIDS incidence by 41% (RR:0.59; 95%CI:0.57-0.61), mortality by 39% (RR:0.61; 95%CI:0.57-0.64), and case fatality rates by 25% (RR:0.75; 95%CI:0.66-0.85) in the cohort, and Programa Bolsa Família effects were considerably stronger among individuals of extremely low-income [reduction of 55% for incidence (RR:0.45, 95% CI:0.42-0.47), 54% mortality (RR:0.46, 95% CI:0.42-0.49), and 37% case-fatality (RR:0.63, 95% CI:0.51 -0.76)], decreasing gradually until having no effect in individuals with higher incomes. Similar effects were observed on HIV notification. Programa Bolsa Família impact was also stronger among women and adolescents. Several sensitivity and triangulation analyses demonstrated the robustness of the results. Conditional cash transfers can significantly reduce AIDS morbidity and mortality in extremely vulnerable populations and should be considered an essential intervention to achieve AIDS-related sustainable development goals by 2030.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil.

Importance: Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. Objective: To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. Design, Setting, and Participants: This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Exposure: Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). Main Outcomes and Measures: The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Results: Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). Conclusions and Relevance: These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

Combining Digital and Molecular Approaches Using Health and Alternate Data Sources in a Next-Generation Surveillance System for Anticipating Outbreaks of Pandemic Potential.

Globally, millions of lives are impacted every year by infectious diseases outbreaks. Comprehensive and innovative surveillance strategies aiming at early alert and timely containment of emerging and reemerging pathogens are a pressing priority. Shortcomings and delays in current pathogen surveillance practices further disturbed informing responses, interventions, and mitigation of recent pandemics, including H1N1 influenza and SARS-CoV-2. We present the design principles of the architecture for an early-alert surveillance system that leverages the vast available data landscape, including syndromic data from primary health care, drug sales, and rumors from the lay media and social media to identify areas with an increased number of cases of respiratory disease. In these potentially affected areas, an intensive and fast sample collection and advanced high-throughput genome sequencing analyses would inform on circulating known or novel pathogens by metagenomics-enabled pathogen characterization. Concurrently, the integration of bioclimatic and socioeconomic data, as well as transportation and mobility network data, into a data analytics platform, coupled with advanced mathematical modeling using artificial intelligence or machine learning, will enable more accurate estimation of outbreak spread risk. Such an approach aims to readily identify and characterize regions in the early stages of an outbreak development, as well as model risk and patterns of spread, informing targeted mitigation and control measures. A fully operational system must integrate diverse and robust data streams to translate data into actionable intelligence and actions, ultimately paving the way toward constructing next-generation surveillance systems.

Perinatal health outcomes of international migrant women in Brazil: A nationwide data linkage study of the CIDACS birth cohort (2011-2018).

BACKGROUND: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. METHODS: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10-49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. RESULTS: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11-1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16-1.28), a newborn who is large for gestational age (1.29, 1.22-1.36), or a newborn with congenital anomalies (1.37, 1.14-1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82-0.95) or have a low birth weight infant (0.74, 0.68-0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. CONCLUSION: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.

The intersection of race/ethnicity and socioeconomic status: inequalities in breast and cervical cancer mortality in 20,665,005 adult women from the 100 Million Brazilian Cohort.

OBJECTIVES: There is limited evidence regarding the impact of race/racism and its intersection with socioeconomic status (SES) on breast and cervical cancer, the two most common female cancers globally. We investigated racial inequalities in breast and cervical cancer mortality and whether SES (education and household conditions) interacted with race/ethnicity. DESIGN: The 100 Million Brazilian Cohort data were linked to the Brazilian Mortality Database, 2004-2015 (n = 20,665,005 adult women). We analysed the association between self-reported race/ethnicity (White/'Parda'(Brown)/Black/Asian/Indigenous) and cancer mortality using Poisson regression, adjusting for age, calendar year, education, household conditions and area of residence. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer mortality rates were higher among Indigenous (adjusted Mortality rate ratio = 1.80, 95%CI 1.39-2.33), Asian (1.63, 1.20-2.22), 'Parda'(Brown) (1.27, 1.21-1.33) and Black (1.18, 1.09-1.28) women vs White women. Breast cancer mortality rates were higher among Black (1.10, 1.04-1.17) vs White women. Racial inequalities in cervical cancer mortality were larger among women of poor household conditions, and low education (P for multiplicative interaction <0.001, and 0.02, respectively). Compared to White women living in completely adequate (3-4) household conditions, the risk of cervical cancer mortality in Black women with 3-4, 1-2, and none adequate conditions was 1.10 (1.01-1.21), 1.48 (1.28-1.71), and 2.03 (1.56-2.63), respectively (Relative excess risk due to interaction-RERI = 0.78, 0.18-1.38). Among 'Parda'(Brown) women the risk was 1.18 (1.11-1.25), 1.68 (1.56-1.81), and 1.84 (1.63-2.08), respectively (RERI = 0.52, 0.16-0.87). Compared to high-educated White women, the risk in high-, middle- and low-educated Black women was 1.14 (0.83-1.55), 1.93 (1.57-2.38) and 2.75 (2.33-3.25), respectively (RERI = 0.36, -0.05-0.77). Among 'Parda'(Brown) women the risk was 1.09 (0.91-1.31), 1.99 (1.70-2.33) and 3.03 (2.61-3.52), respectively (RERI = 0.68, 0.48-0.88). No interactions were found for breast cancer. CONCLUSION: Low SES magnified racial inequalities in cervical cancer mortality. The intersection between race/ethnicity, SES and gender needs to be addressed to reduce racial health inequalities.

Incidence and risk factors of tuberculosis among 420 854 household contacts of patients with tuberculosis in the 100 Million Brazilian Cohort (2004-18): a cohort study.

BACKGROUND: Although household contacts of patients with tuberculosis are known to be particularly vulnerable to tuberculosis, the published evidence focused on this group at high risk within the low-income and middle-income country context remains sparse. Using nationwide data from Brazil, we aimed to estimate the incidence and investigate the socioeconomic and clinical determinants of tuberculosis in a cohort of contacts of tuberculosis patients. METHODS: In this cohort study, we linked individual socioeconomic and demographic data from the 100 Million Brazilian Cohort to mortality data and tuberculosis registries, identified contacts of tuberculosis index patients diagnosed from Jan 1, 2004 to Dec 31, 2018, and followed up the contacts until the contact's subsequent tuberculosis diagnosis, the contact's death, or Dec 31, 2018. We investigated factors associated with active tuberculosis using multilevel Poisson regressions, allowing for municipality-level and household-level random effects. FINDINGS: We studied 420 854 household contacts of 137 131 tuberculosis index patients. During the 15 years of follow-up (median 4·4 years [IQR 1·9-7·6]), we detected 8953 contacts with tuberculosis. The tuberculosis incidence among contacts was 427·8 per 100 000 person-years at risk (95% CI 419·1-436·8), 16-times higher than the incidence in the general population (26·2 [26·1-26·3]) and the risk was prolonged. Tuberculosis incidence was associated with the index patient being preschool aged (<5 years; adjusted risk ratio 4·15 [95% CI 3·26-5·28]) or having pulmonary tuberculosis (2·84 [2·55-3·17]). INTERPRETATION: The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination. FUNDING: Wellcome Trust and Brazilian Ministry of Health.

Postnatal growth in small vulnerable newborns: a longitudinal study of 2 million Brazilians using routine register-based linked data.

BACKGROUND: Preterm, low-birth weight (LBW) and small-for-gestational age (SGA) newborns have a higher frequency of adverse health outcomes, including linear and ponderal growth impairment. OBJECTIVE: To describe the growth trajectories and to estimate catch-up growth during the first 5 y of life of small newborns according to 3 vulnerability phenotypes (preterm, LBW, SGA). METHODS: Longitudinal study using linked data from the 100 Million Brazilian Cohort baseline, the Brazilian National Live Birth System (SINASC), and the Food and Nutrition Surveillance System (SISVAN) from 2011 to 2017. We estimated the length/height-for-age (L/HAZ) and weight-for-age z-score (WAZ) trajectories from children of 6-59 mo using the linear mixed model for each vulnerable newborn phenotype. Growth velocity for both L/HAZ and WAZ was calculated considering the change (Δ) in the mean z-score between 2 time points. Catch-up growth was defined as a change in z-score > 0.67 at any time during follow-up. RESULTS: We analyzed 2,021,998 live born children and 8,726,599 observations. The prevalence of at least one of the vulnerable phenotypes was 16.7% and 0.6% were simultaneously preterm, LBW, and SGA. For those born at term, all phenotypes had a period of growth recovery from 12 mo. For preterm infants, the onset of L/HAZ growth recovery started later at 24 mo and the growth trajectories appear to be lower than those born at term, a condition aggravated among children with the 3 phenotypes. Preterm and female infants seem to experience slower growth recovery than those born at term and males. The catch-up growth occurs at 24-59 mo for males preterm: preterm + AGA + NBW (Δ = 0.80), preterm + AGA + LBW (Δ = 0.88), and preterm + SGA + LBW (Δ = 1.08); and among females: term + SGA + NBW (Δ = 0.69), term + AGA + LBW (Δ = 0.72), term + SGA + LBW (Δ = 0.77), preterm + AGA + LBW (Δ = 0.68), and preterm + SGA + LBW (Δ = 0.83). CONCLUSIONS: Children born preterm seem to reach L/HAZ and WAZ growth trajectories lower than those attained by children born at term, a condition aggravated among the most vulnerable.

A scaling investigation of urban form features in Latin America cities.

This paper examines scaling behaviors of urban landscape and street design metrics with respect to city population in Latin America. We used data from the SALURBAL project, which has compiled and harmonized data on health, social, and built environment for 371 Latin American cities above 100,000 inhabitants. These metrics included total urbanized area, effective mesh size, area in km2 and number of streets. We obtained scaling relations by regressing log(metric) on log (city population). The results show an overall sub-linear scaling behavior of most variables, indicating a relatively lower value of each variable in larger cities. We also explored the potential influence of colonization on the current built environment, by analyzing cities colonized by Portuguese (Brazilian cities) or Spaniards (Other cities in Latin America) separately. We found that the scaling behaviors are similar for both sets of cities.

Participation in Conditional Cash Transfer Program During Pregnancy and Birth Weight-Related Outcomes.

Importance: There is limited evidence of the association of conditional cash transfers, an important strategy to reduce poverty, with prevention of adverse birth-related outcomes. Objective: To investigate the association between receiving benefits from the Bolsa Família Program (BFP) and birth weight indicators. Design, Setting, and Participants: This cohort study used a linked data resource, the Centro de Integracao de Dados e Conhecimentos Para Saude (CIDACS) birth cohort. All live-born singleton infants born to mothers registered in the cohort between January 2012 and December 2015 were included. Each analysis was conducted for the overall population and separately by level of education, self-reported maternal race, and number of prenatal appointments. Data were analyzed from January 3 to April 24, 2023. Exposure: Live births of mothers who had received BFP until delivery (for a minimum of 9 months) were classified as exposed and compared with live births from mothers who did not receive the benefit prior to delivery. Main Outcomes and Measures: Low birth weight (LBW), birth weight in grams, and small for gestational age (SGA) were evaluated. Analytical methods used included propensity score estimation, kernel matching, and weighted logistic and linear regressions. Race categories included Parda, which translates from Portuguese as "brown" and is used to denote individuals whose racial background is predominantly Black and those with multiracial or multiethnic ancestry, including European, African, and Indigenous origins. Results: A total of 4 277 523 live births (2 085 737 females [48.8%]; 15 207 among Asian [0.4%], 334 225 among Black [7.8%], 29 115 among Indigenous [0.7%], 2 588 363 among Parda [60.5%], and 1 310 613 among White [30.6%] mothers) were assessed. BFP was associated with an increase of 17.76 g (95% CI, 16.52-19.01 g) in birth weight. Beneficiaries had an 11% lower chance of LBW (odds ratio [OR], 0.89; 95% CI, 0.88-0.90). BFP was associated with a greater decrease in odds of LBW among subgroups of mothers who attended fewer than 7 appointments (OR, 0.85; 95% CI, 0.84-0.87), were Indigenous (OR, 0.73; 95% CI, 0.61-0.88), and had 3 or less years of education (OR, 0.76; 95% CI, 0.72-0.81). There was no association between BFP and SGA, except among less educated mothers, who had a reduced risk of SGA (OR, 0.83; 95% CI, 0.79-0.88). Conclusions and Relevance: This study found that BFP was associated with increased birth weight and reduced odds of LBW, with a greater decrease in odds of LBW among higher-risk groups. These findings suggest the importance of maintaining financial support for mothers at increased risk of birth weight-related outcomes.

The effect of primary health care on AIDS incidence and mortality: a cohort study of 3.4 million Brazilians.

Background: Primary Health Care (PHC) is essential for the health and wellbeing of people living with HIV/AIDS. This study evaluated the effects of one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality. Methods: A retrospective cohort study carried out in Brazil, from January 1 2007 to December 31 2015. We conducted a quasi-experimental effect evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the effect of FHS on AIDS incidence and mortality and comparing outcomes between residents of municipalities with no FHS coverage with those in municipalities with full FHS coverage. We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated FHS effect by sex and age, and performed a wide range of sensitivity and triangulation analyses. Findings: FHS coverage was associated with lower AIDS incidence (rate ratio [RR]:0.76, 95%CI:0.68-0.84) and mortality (RR:0.68,95%CI:0.56-0.82). FHS effect was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR 0.62, 95%CI:0.53-0.72) and mortality (RR 0.56, 95%CI:0.43-0.72). Conclusions: AIDS should be an avoidable outcome for most people living with HIV today, and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.

Maternal and congenital syphilis attributable to ethnoracial inequalities: a national record-linkage longitudinal study of 15 million births in Brazil.

BACKGROUND: This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical construct that functions as an essential tool of racism and its manifestations. METHODS: We linked routinely collected data from Jan 1, 2012 to Dec 31, 2017 to conduct a population-based study in Brazil. We estimated the attributable fraction of race (skin colour) for the entire population and specific subgroups compared with White women using adjusted logistic regression. We also obtained the attributable fraction of the intersection between two social markers (race and education) and compared it with White women with more than 12 years of education as the baseline. FINDINGS: Of 15 810 488 birth records, 144 564 women had maternal syphilis and 79 580 had congenital syphilis. If all women had the same baseline risk as White women, 35% (95% CI 34·89-36·10) of all maternal syphilis and 41% (40·49-42·09) of all congenital syphilis would have been prevented. Compared with other ethnoracial categories, these percentages were higher among Parda/Brown women (46% [45·74-47·20] of maternal syphilis and 52% [51·09-52·93] of congenital syphilis would have been prevented) and Black women (61% [60·25-61·75] of maternal syphilis and 67% [65·87-67·60] of congenital syphilis would have been prevented). If all ethnoracial groups had the same risk as White women with more than 12 years of education, 87% of all maternal syphilis and 89% of all congenital syphilis would have been prevented. INTERPRETATION: Only through effective control of maternal syphilis among populations at higher risk (eg, Black and Parda/Brown women with lower educational levels) can WHO's global health initiative to eliminate mother-to-child transmission of syphilis be made feasible. Recognising that racism and other intersecting forms of oppression affect the lives of minoritised groups and advocating for actions through the lens of intersectionality is imperative for attaining and guaranteeing health equity. Achieving health equality needs to be addressed to achieve syphilis control. Given the scale and complexity of the problem (which is unlikely to be unique to Brazil), structural issues and social markers of oppression, such as race and education, must be considered to prevent maternal and congenital syphilis and improve maternal and child outcomes globally. FUNDING: Wellcome Trust, CNPq-Brazil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Maternal and child nutrition programme of investigation within the 100 Million Brazilian Cohort: study protocol.

INTRODUCTION: There is a limited understanding of the early nutrition and pregnancy determinants of short-term and long-term maternal and child health in ethnically diverse and socioeconomically vulnerable populations within low-income and middle-income countries. This investigation programme aims to: (1) describe maternal weight trajectories throughout the life course; (2) describe child weight, height and body mass index (BMI) trajectories; (3) create and validate models to predict childhood obesity at 5 years of age; (4) estimate the effects of prepregnancy BMI, gestational weight gain (GWG) and maternal weight trajectories on adverse maternal and neonatal outcomes and child growth trajectories; (5) estimate the effects of prepregnancy BMI, GWG, maternal weight and interpregnancy BMI changes on maternal and child outcomes in the subsequent pregnancy; and (6) estimate the effects of maternal food consumption and infant feeding practices on child nutritional status and growth trajectories. METHODS AND ANALYSIS: Linked data from four different Brazilian databases will be used: the 100 Million Brazilian Cohort, the Live Births Information System, the Mortality Information System and the Food and Nutrition Surveillance System. To analyse trajectories, latent-growth, superimposition by translation and rotation and broken stick models will be used. To create prediction models for childhood obesity, machine learning techniques will be applied. For the association between the selected exposure and outcomes variables, generalised linear models will be considered. Directed acyclic graphs will be constructed to identify potential confounders for each analysis investigating potential causal relationships. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committees of the authors' institutions. The linkage will be carried out in a secure environment. After the linkage, the data will be de-identified, and pre-authorised researchers will access the data set via a virtual private network connection. Results will be reported in open-access journals and disseminated to policymakers and the broader public.