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Background: Home visiting programmes can support child development and reduce inequalities, but failure to identify the most vulnerable families can undermine such efforts. We examined whether there are strong predictors of poor child development that could be used to screen pregnant women in primary health care settings to target early interventions in a Brazilian population. Considering selected predictors, we assessed coverage and focus of a large-scale home visiting programme named Primeira Infância Melhor (PIM)., Methods: We undertook a prospective cohort study on 3603 children whom we followed from gestation to age four years. We then used 27 potential socioeconomic, psychosocial, and clinical risk factors measurable during pregnancy to predict child development, which was assessed by the Battelle Developmental Inventory (BDI) at the age of four years. We compared the results from a Bonferroni-adjusted conditional inference tree with exploratory linear regression and principal component analysis (PCA), and we conducted external validation using data from a second cohort from the same population. Lastly, we assessed PIM coverage and focus by linking 2015 cohort data with PIM databases., Results: The decision tree analyses identified maternal schooling as the most important variable for predicting BDI, followed by paternal schooling. Based on these variables, a group of 214 children who had the lowest mean BDI (BDI = -0.48; 95% confidence interval (CI) = -0.63, -0.33) was defined by mothers with ≤5 years and fathers with ≤4 years of schooling. Maternal and paternal schooling were also the strongest predictors in the exploratory analysis using regression and PCA, showing linear associations with the outcome. However, their capacity to explain outcome variance was low, with an adjusted R 2 of 5.3% and an area under the receiver operating characteristic curve of 0.62 (95% CI = 0.60, 0.64). External validation showed consistent results. We also provided an online screening tool using parental schooling data to support programme's targeting. PIM coverage during pregnancy was low, but the focus was adequate, especially among families with longer enrolment, indicating families most in need received higher dosage., Conclusions: Information on maternal and paternal schooling can improve the focus of home visiting programmes if used for initial population-level screening of pregnant women in Brazil. However, enrolment decisions require complementary information on parental resources and direct interactions with families to jointly decide on inclusion., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Women's health and well-being (WHW) have been receiving growing attention, but limited progress has been made on how to measure its different domains in low- and middle-income countries (LMICs). We used data from five long-term birth cohorts in Brazil, Guatemala, the Philippines and South Africa to explore different domains of adult WHW, and how these domains relate to early life exposures., Methods: Based upon an a priori conceptualisation of eight postulated WHW outcomes available in the data, we grouped them as follows: human capital (intelligence quotient, schooling, height, and teenage childbearing), metabolic health (body mass index and metabolic syndrome score), and psychological (happiness and Self-Reported Questionnaire (SRQ) scores). Correlation analyses confirmed the variables theoretically belonging to the same dimension of WHW were statistically related. We then applied principal component analysis to each group of variables separately and used the first principal component as a summary quantitative measure of the corresponding WHW dimension. Finally, we assessed the association of each domain with a range of early-life factors: wealth, maternal education, maternal height, water, and sanitation, birthweight, length at two years and development quotient in mid-childhood., Results: The three domains were largely uncorrelated. Early determinants were positively associated with human capital, while birth order was negatively associated. Fewer associations were found for the metabolic or psychological components. Birthweight and weight at age two years were inversely associated with metabolic health. Maternal education was associated with better psychological health., Conclusions: Our findings indicate that WHW is multidimensional, with most women in the cohorts being compromised in one or more domains while few women scored highly in all three domains. Our analyses are limited by lack of data on adolescent exposures and on other relevant WHW dimensions such as safety, agency, empowerment, and violence. Further research is needed in LMICs for identifying and measuring the multiple domains of WHW., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: ADS reports grants from Bill and Melinda Gates Foundation. ZAB reports grants from the International Development Research Centre (reproductive, maternal, newborn, child, and adolescent health in conflict settings: case studies to inform implementation of interventions) and Countdown to 2030–UNICEF., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Maternal mental health during different stages of life can have a significant impact on a child's cognitive development. This study aimed to investigate the association between maternal CMD at two distinct stages of the offspring's life (at 3 months and 11 years) and their IQ scores at 6 and 18 years across two birth cohorts. The study utilized data from two Brazilian birth cohorts: the 1993 cohort (full sample: N = 3719, subsample: N = 436), and the 2004 Pelotas Birth Cohort (N = 3440). IQ assessments were conducted at ages 18 and 6, employing the Wechsler Adult Intelligence Scale, third version (WAIS-III), and Wechsler Intelligence Scale for Children, third version (WISC-III), respectively. The presence of maternal CMD at 3 months and 11 years of age was evaluated using the Brazilian version of the Self-Reporting Questionnaire (SRQ-20). After adjustment, participants whose mothers experienced CMD at 3 months had average IQ scores 1.74 (95 % CI: -2.83 to -0.67) and 2.79 (95 % CI: -5.54 to -0.04) points lower at ages 6 (2004 cohort) and 18 (1993 cohort subsample), respectively. Furthermore, in the 1993 cohort (both full and subsample), maternal CMD at 11 years was associated with lower IQ scores at age 18. Understanding the mechanisms underlying this association, emphasized by these findings, is crucial for promoting children's cognitive development, educational achievement, and overall well-being., Competing Interests: Declaration of competing interest All authors contributed to study design, data analysis, data interpretation, and drafting and revision of the manuscript, and gave final approval of the version to be submitted for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01-1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background: The scale-up of parenting programmes to support early childhood development (ECD) is poorly understood. Little is known about how and when early interventions are most effective. Sustainability of ECD programming requires a better understanding of the mechanisms of real-world interventions. We examined the effects on caregiving practices of Primeira Infância Melhor (PIM), a state-wide home-visiting programme in Brazil., Methods: This propensity score matched, longitudinal, quasiexperimental study uses data from the 2015 Pelotas Birth Cohort. We matched children who received PIM at any age with other cohort children on 25 key covariates. Sensitivity, guidance and responsiveness were assessed using video-recorded play tasks. Coerciveness and the parent-child relationship were assessed using the Parenting and Family Adjustment Scales. All parenting outcomes were examined at age 4 years. Separate moderation analyses were conducted for each effect modifier: family income, child age and duration of participation., Results: Out of 4275 children in the cohort, 797 were enrolled in PIM up to age 4 years. 3018 children (70.6%) were included in the analytic sample, of whom 587 received PIM and 2431 were potential controls. We found a positive effect of PIM on responsiveness (β=0.08, 95% CIs 0.002 to 0.16) and sensitivity (β=0.10, 95% CIs 0.02 to 0.19). No effect was found for any secondary outcomes. Moderation analyses revealed a stronger positive effect on sensitivity for low-income parents (β=0.18, 95% CIs 0.03 to 0.34)., Conclusion: A state-wide, home-visiting programme in Brazil improved aspects of responsive caregiving. Effects were more pronounced for low-income families, suggesting benefits of purposeful targeting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant ( p < 5 × 10 -8 ) and suggestive ( p < 1 × 10 -6 ) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose ( FOXP1, MBOAT4, SKP2, STIM1, STX4 ), brain ( BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A ), and liver ( BRI3, FOXP1 ) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects., Competing Interests: IN is now employed by Celgene. BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. SA is employed by and holds equity in 23andMe, Inc. Authors BK, MW, and CGa were employed by Helmholtz Zentrum München. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de las Fuentes, Schwander, Brown, Bentley, Winkler, Sung, Munroe, Miller, Aschard, Aslibekyan, Bartz, Bielak, Chai, Cheng, Dorajoo, Feitosa, Guo, Hartwig, Horimoto, Kolčić, Lim, Liu, Manning, Marten, Musani, Noordam, Padmanabhan, Rankinen, Richard, Ridker, Smith, Vojinovic, Zonderman, Alver, Boissel, Christensen, Freedman, Gao, Giulianini, Harris, He, Hsu, Kühnel, Laguzzi, Li, Lyytikäinen, Nolte, Poveda, Rauramaa, Riaz, Robino, Sofer, Takeuchi, Tayo, van der Most, Verweij, Ware, Weiss, Wen, Yanek, Zhan, Amin, Arking, Ballantyne, Boerwinkle, Brody, Broeckel, Campbell, Canouil, Chai, Ida Chen, Chen, Chitrala, Concas, de Faire, de Mutsert, de Silva, de Vries, Do, Faul, Fisher, Floyd, Forrester, Friedlander, Girotto, Gu, Hallmans, Heikkinen, Heng, Homuth, Hunt, Ikram, Jacobs, Kavousi, Khor, Kilpeläinen, Koh, Komulainen, Langefeld, Liang, Liu, Liu, Lohman, Mägi, Manichaikul, McKenzie, Meitinger, Milaneschi, Nauck, Nelson, O’Connell, Palmer, Pereira, Perls, Peters, Polašek, Raitakari, Rice, Rice, Rich, Sabanayagam, Schreiner, Shu, Sidney, Sims, Smith, Starr, Strauch, Tai, Taylor, Tsai, Uitterlinden, van Heemst, Waldenberger, Wang, Wei, Wilson, Xuan, Yao, Yu, Yuan, Zhao, Becker, Bonnefond, Bowden, Cooper, Deary, Divers, Esko, Franks, Froguel, Gieger, Jonas, Kato, Lakka, Leander, Lehtimäki, Magnusson, North, Ntalla, Penninx, Samani, Snieder, Spedicati, van der Harst, Völzke, Wagenknecht, Weir, Wojczynski, Wu, Zheng, Zhu, Bouchard, Chasman, Evans, Fox, Gudnason, Hayward, Horta, Kardia, Krieger, Mook-Kanamori, Peyser, Province, Psaty, Rudan, Sim, Smith, van Dam, van Duijn, Wong, Arnett, Rao, Gauderman, Liu, Morrison, Rotter and Fornage.)

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into ten sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), extensions and additional analyses, data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 24 months., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Burgess S et al.)

Background: Glycerol is a cryoprotectant widely used in the freezing of mammalian semen, but no study has demonstrated its optimum concentration and the appropriate exposure time for equine species., Objective: To demonstrate that the exposure time (15, 30, 45, 60, 75 and 90 min) versus concentration (2, 3, 4 and 5%) of the cryoprotectant glycerol influences the freezing success of equine semen., Materials and Methods: The ejaculate of 12 stallions were frozen in different glycerol concentrations following different exposure times. The thawed sperm was evaluated for kinetic parameters using a Computer Assisted Semen Analysis (CASA) system and cell feature parameters were assessed by flow cytometry., Results: Considering the total and progressive motility of the spermatozoa, we concluded that protocols using 5% glycerol for 15 and 30 min exposure, 4% glycerol for 45 min exposure and 3% glycerol for 90 min exposure generated the best results., Conclusion: We suggest the use of any of these protocols for a better cryopreservation of equine semen. Doi: 10.54680/fr23410110412.

Background: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment has a causal effect on an outcome . Even if the instrument satisfies the three core IV assumptions of relevance, independence, and exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of on . Sufficient assumptions for this include homogeneity in the causal effect of on ; homogeneity in the association of with ; and no effect modification., Methods: We describe the no simultaneous heterogeneity assumption, which requires the heterogeneity in the - causal effect to be mean independent of (i.e., uncorrelated with) both and heterogeneity in the - association. This happens, for example, if there are no common modifiers of the - effect and the - association, and the - effect is additive linear. We illustrate the assumption of no simultaneous heterogeneity using simulations and by re-examining selected published studies., Results: Under no simultaneous heterogeneity, the Wald estimand equals the ACE even if both homogeneity assumptions and no effect modification (which we demonstrate to be special cases of-and therefore stronger than-no simultaneous heterogeneity) are violated., Conclusions: The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs. Since this assumption is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The composite coverage index (CCI) provides an integrated perspective towards universal health coverage in the context of reproductive, maternal, newborn and child health. Given the sample design of most household surveys does not provide coverage estimates below the first administrative level, approaches for achieving more granular estimates are needed. We used a model-based geostatistical approach to estimate the CCI at multiple resolutions in Peru., Methods: We generated estimates for the eight indicators on which the CCI is based for the departments, provinces, and areas of 5 × 5 km of Peru using data from two national household surveys carried out in 2018 and 2019 plus geospatial covariates. Bayesian geostatistical models were fit using the INLA-SPDE approach. We assessed model fit using cross-validation at the survey cluster level and by comparing modelled and direct survey estimates at the department-level., Results: CCI coverage in the provinces along the coast was consistently higher than in the remainder of the country. Jungle areas in the north and east presented the lowest coverage levels and the largest gaps between and within provinces. The greatest inequalities were found, unsurprisingly, in the largest provinces where populations are scattered in jungle territory and are difficult to reach., Conclusions: Our study highlighted provinces with high levels of inequality in CCI coverage indicating areas, mostly low-populated jungle areas, where more attention is needed. We also uncovered other areas, such as the border with Bolivia, where coverage is lower than the coastal provinces and should receive increased efforts. More generally, our results make the case for high-resolution estimates to unveil geographic inequities otherwise hidden by the usual levels of survey representativeness., (© 2022. The Author(s).)

Background: Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction., Methods: We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure., Results: Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous, and the effect of the exposure on the outcome is nonlinear on the additive scale. For a binary exposure, the exposure-outcome effect is necessarily additive linear, so the homogeneity condition is sufficient., Conclusions: For binary instruments, instrument-exposure additive homogeneity identifies the ADE if the exposure is also binary. Otherwise, additional assumptions (such as additive linearity of the exposure-outcome effect) are required., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II A muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention., (© 2022. The Author(s).)

Studies leveraging gene-environment (GxE) interactions within Mendelian randomization (MR) analyses have prompted the emergence of two similar methodologies: MR-GxE and MR-GENIUS. Such methods are attractive in allowing for pleiotropic bias to be corrected when using individual instruments. Specifically, MR-GxE requires an interaction to be explicitly identified, while MR-GENIUS does not. We critically examine the assumptions of MR-GxE and MR-GENIUS in the absence of a pre-defined covariate, and propose sensitivity analyses to evaluate their performance. Finally, we explore the effect of body mass index (BMI) upon systolic blood pressure (SBP) using data from the UK Biobank, finding evidence of a positive effect of BMI on SBP. We find both approaches share similar assumptions, though differences between the approaches lend themselves to differing research settings. Where a suitable gene-by-covariate interaction is observed MR-GxE can produce unbiased causal effect estimates. MR-GENIUS can circumvent the need to identify interactions, but as a consequence relies on either the MR-GxE assumptions holding globally, or additional information with respect to the distribution of pleiotropic effects in the absence of an explicitly defined interaction covariate., Competing Interests: The authors have declared that no competing interests exist.

By March 3, 2022, the COVID-19 pandemic has caused more than 399 million infections and claimed the lives of more than five million people worldwide. To reduce infection rates, a series of prevention measures indicated by the World Health Organization (WHO) were adopted by countries, including the use of masks. This study aims to describe mask use in Brazil via data analysis from the EPICOVID19-BR, a population-based study conducted in 133 cities in the country in four phases between March and August 2020. The proportion of individuals who reported wearing a mask when they left their homes was 97.9% (95%CI: 97.8-98.0). The interviewer did not see interviewees' mask in 50% (95%CI: 49.9-51.1) of the cases at the time of the interview. However, between phase one and four of the survey, we observed a 4.4% decrease in the proportion of interviewees who failed to wear masks at the time of the interview. Mask non-visualization was more prominent in women, participants aged 10-19 and 20-29 years of indigenous, black, and brown skin color, and those with elementary and high school education and in the Central-West Region. The use of cloth masks showed a 91.4% predominance (95%CI: 91.2-1.5) with a 4.9% increase between phases 1 and 4. The results of the study bring important information to reinforce COVID-19 control policies in Brazil. The high percentage of people who failed to wear masks at the time of the interview suggests that it is still important to reinforce prevention and self-care, rather than relating mask wear to a mandatory measure.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past., Competing Interests: Declaration of interests REB serves on the Board of Vitamin Angels, a non-profit charitable organisation supporting maternal and child nutrition services in LMICs. AS and ADS report grants from Bill and Melinda Gates Foundation. AS reports grants from the Wellcome Trust. ZAB reports grants from the International Development Research Centre (reproductive, maternal, newborn, child, and adolescent health in conflict settings: case studies to inform implementation of interventions) and Countdown to 2030–UNICEF. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood., Competing Interests: Declaration of interests REB serves on the Board of Directors of Vitamin Angels, a non-profit charitable organisation supporting maternal and child nutrition services in low-income and middle-income countries. ME reports a grant from AstraZeneca for the Young Health Programme, and personal fees from Prudential, outside the submitted work. REB, FV, LH, LL, ADS, DYo, and DYe report grants from the Bill & Melinda Gates Foundation. LH and DYo report grants from USAID, outside the submitted work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic.

Background: A large-scale parenting programme with weekly home visits (Primeira Infância Melhor (PIM)) has been implemented in the south of Brazil for nearly two decades, but lacks evaluation of its effects on early childhood development (ECD). This quasi-experimental study aimed to assess the effects of PIM in real-life settings within a population-based birth cohort study., Methods: Data from the 2015 Pelotas Birth Cohort Study and the state programme information system were linked to identify study children who received PIM. Propensity score matching was used to create a comparable control group (using one-to-one matching) to estimate the effect of PIM on ECD measured at age 4 years. First, the impact of any enrolment in PIM was evaluated; then the intervention group was stratified according to whether enrolment occurred during pregnancy or after birth. Double adjustment was applied in linear regression to analyse child development scores, and Poisson regression for delayed development (below the 10th percentile of whole cohort). Effect modification due to family income was explored., Results: There was no evidence that any enrolment in PIM (601 pairs) by age 4 years was associated with child development. However, PIM starting during pregnancy (estimated for 121 pairs) predicted higher development scores (0.27 SD; 95% CI 0.02 to 0.52), and 71% lower prevalence of delayed development (prevalence ratio=0.29; 95% CI 0.13 to 0.69), compared with the control group. There was strong statistical evidence (p=0.003, test of interaction) that the effect of PIM starting in pregnancy was larger than when starting after birth (480 pairs). The effect of PIM starting during pregnancy was found to be restricted to poorer families., Conclusions: In a real-life setting, PIM was effective only when starting during pregnancy and only for poorer families. A higher-quality programme might be more effective with a broader population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: To describe the evolution of seropositivity in the State of Rio Grande do Sul, Brazil, through 10 consecutive surveys conducted between April 2020 and April 2021., Methods: Nine cities covering all regions of the State were studied, 500 households in each city. One resident in each household was randomly selected for testing. In survey rounds 1-8 we used the rapid WONDFO SARS-CoV-2 Antibody Test (Wondfo Biotech Co., Guangzhou, China). In rounds 9-10, we used a direct ELISA test that identifies IgG to the viral S protein (S-UFRJ). In terms of social distancing, individuals were asked three questions, from which we generated an exposure score using principal components analysis., Results: Antibody prevalence in early April 2020 was 0.07%, increasing to 10.0% in February 2021, and to 18.2% in April 2021. In round 10, self-reported whites showed the lowest seroprevalence (17.3%), while indigenous individuals presented the highest (44.4%). Seropositivity increased by 40% when comparing the most with the least exposed., Conclusions: The proportion of the population already infected by SARS-Cov-2 in the state is still far from any perspective of herd immunity and the infection affects population groups in very different levels.

Objective: To evaluate the prevalence of reports of symptoms of COVID-19 among individuals with and without antibodies and identify those with greater capability to predict the presence of antibodies against SARS-CoV-2., Methods: The study uses data collected in phases 5 to 8 of Epicovid-19-RS. The presence of antibodies against SARS-CoV-2 was evaluated by a rapid test. The occurrence of cough, fever, palpitations, sore throat, difficulty breathing, changes in taste and smell, vomiting, diarrhea, body pain, shaking, and headache since March 2020 was also evaluated. Then, the capability to predict the evaluated symptoms concerning the presence of antibodies was calculated., Results: A total of 18,000 individuals were interviewed and 181 had antibodies against COVID-19 in phases 5 to 8. The proportion of asymptomatic individuals was 19.9% among participants with antibodies and 49.7% among those without antibodies. All symptoms were reported more frequently by individuals with antibodies. The division of the prevalence of symptoms among individuals with antibodies by the prevalence among individuals without antibodies showed the following prevalence ratios: for changes in smell or taste (9.1), fever (4.2), tremors (3.9), breathing difficulty (3.2) and cough (2.8 times). Anosmia and fever were the symptoms with a greater capability to predict the presence of antibodies., Conclusion: The prevalence of symptoms was higher among individuals with antibodies against SARS-CoV-2. The proportion of asymptomatic individuals was low. Altered smell or taste and fever were the symptoms that most predict the presence of antibodies. These results can help to identify probable cases, contributing to the clinical diagnosis and screening of patients for testing and isolation guidance in positive cases, especially in scenarios of the scarcity of diagnostic COVID-19 tests.

Background: Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables., Methods: We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR., Results: In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index., Conclusions: Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Spousal comparisons have been proposed as a design that can both reduce confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies. We demonstrated that the WSP model can reduce confounding but may be susceptible to collider bias arising from conditioning on assorted spouse pairs. Analyses using UK Biobank spouse pairs found that WSP genetic association estimates were smaller than estimates from random pairs for height, educational attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI. WSP models, like other within-family models, may reduce confounding from demographic factors in genetic association estimates, and so could be useful for triangulating evidence across study designs to assess the robustness of findings. However, WSP estimates should be interpreted with caution due to potential collider bias., Competing Interests: The authors declare no competing interests.

Objectives: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil., Methods: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses., Results: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant., Conclusions: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

This study aims to assess the association between mode of delivery and human capital among young adults enrolled in the 1982 and 1993 Pelotas birth cohorts, Rio Grande do Sul State, Brasil. In 1982 and 1993, the maternity hospitals of the municipality were daily visited, the births identified, and those live births, whose family lived in the urban area of Pelotas, were examined and their mothers interviewed. Information on mode of delivery, vaginal or cesarean, was provided by the mother in the perinatal study. Performance in intelligence tests achieved schooling and income were evaluated in the 30 years visit at the 1982 cohort. At the 1993 cohort, schooling and income were assessed at the 22 years visit, whereas IQ was evaluated at 18 years. Tobacco smoking in adulthood and type of school was used as negative outcomes to strength causal inference. Initially, cesarean section was positively associated with human capital at adulthood, with the exception of income in the 1993 cohort. After controlling for confounders, the magnitude of the associations was strongly reduced, and the regression coefficients were close to the null value. The negative outcome analysis showed that, after controlling for confounding variables, the mode of delivery was not associated with tobacco smoking and type of school. Suggesting that the variables included in the regression model to control for confounding, provided an adequate adjustment and it is unlikely that the results are due to residual confounding by socioeconomic status. On the other hand, considering the short- and long-term risks and the epidemic of cesarean sections, measures should be implemented to reduce its prevalence.

Background: Growth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored., Objectives: We examined the association between growth in childhood and adult human capital in 5 low- and middle-income countries (LMICs)., Methods: We analyzed data from 9503 participants in 6 prospective birth cohorts from 5 LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We used linear and quasi-Poisson regression models to assess the associations between measures of height and relative weight at 4 age intervals [birth, age ∼2 y, midchildhood (MC), adulthood] and 2 dimensions of adult human capital [schooling attainment and Intelligence Quotient (IQ)]., Results: Meta-analysis of site- and sex-specific estimates showed statistically significant associations between size at birth and height at ∼2 y and the 2 outcomes (P < 0.001). Weight and length at birth and linear growth from birth to ∼2 y of age (1 z-score difference) were positively associated with schooling attainment (β: 0.13; 95% CI: 0.08, 0.19, β: 0.17; 95% CI: 0.07, 0.32, and β: 0.25, 95% CI: 0.10, 0.40, respectively) and adult IQ (β: 0.74, 95% CI: 0.35, 1.14, β: 0.73, 95% CI: 0.35, 1.10, and β: 1.52, 95% CI: 0.96, 2.08, respectively). Linear growth from age 2 y to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood, MC, and adulthood was not associated with either outcome., Conclusions: Linear growth in the first 1000 d is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight across the life course were not associated with schooling and IQ in adulthood., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Routine immunization during pandemics can be harmed. This study estimated the influenza vaccination coverage in older adults during the COVID-19 through the EPICOVID-19, a population-based study conducted in 133 cities from the 26 Brazilian states and Federal District. We selected 25 census tracts per city, with probability proportional to the tract's size, ten households by census tract, and one random individual interviewed. A total of 8,265 older adults (≥60 years old) were interviewed and asked whether they had been vaccinated against flu in 2020. Vaccination coverage was 82.3% (95% CI: 80.1-84.2) with no difference by gender, age, and region; higher vaccination coverage was observed among the wealthiest (84.7% versus 80.1% in the poorest) and among the more educated (87.3% versus 83.2% less educated); lower coverage among indigenous (56.9% versus > 80% among other ethnic groups). A positive association was identified with the number of comorbidities among men but not among women. Most of the population was vaccinated (97.5%) in the public health system. The private network was chosen mainly in the South by the wealthiest and more educated. Vaccination coverage was seven percentage points lower than the government target (90%), and inequalities should be reversed in future campaigns.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

Background: Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-2 often rely on point-of-care tests that provide immediate results to participants. Yet, little is known on how long rapid tests remain positive after the COVID-19 episode, or how much variability exists across different brands and even among batches of the same test., Methods: In November 2020, we assessed the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October. All subjects provided finger prick blood samples for two batches (A and B) of the Wondfo lateral-flow IgG/IgM test, and dried blood spot samples for the S-UFRJ ELISA test., Results: Overall sensitivity levels were 92.5% (95% CI 86.6-96.3), 63.2% (95% CI 54.4-71.4) and 33.8% (95% CI 25.9-42.5) for the S-UFRJ test, Wondfo A and Wondfo B tests, respectively. There was no evidence of a decline in the positivity of S-UFRJ with time since the diagnosis, but the two Wondfo batches showed sharp reductions to as low as 41.9% and 19.4%, respectively, for subjects with a positive PCR in June or earlier. Positive results for batch B of the rapid test were 35% to 54% lower than for batch A at any given month of diagnosis., Interpretation: Whereas the ELISA test showed high sensitivity and stability of results over the five months of the study, both batches of the rapid test showed substantial declines, with one of the batches consistently showing lower sensitivity levels than the other. ELISA tests based on dried-blood spots are an inexpensive alternative to rapid lateral-flow tests in large-scale epidemiological studies., Funding: The study was funded by the "Todos Pela Saúde" initiative, Instituto Serrapilheira, Brazilian Ministry of Health, Brazilian Collective Health Association (ABRASCO) and the JBS S.A. initiative 'Fazer o Bem Faz Bem'., Competing Interests: Conflicts of interest None., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To estimate the prevalence of SARS-CoV-2 antibodies and the adherence to measures of social distancing in children and adolescents studied in three national surveys conducted in Brazil between May-June 2020., Methods: Three national serological surveys were conducted in 133 sentinel cities located in all 27 Federative Units. Multistage probability sampling was used to select 250 individuals per city. The total sample size in age ranges 0-9 and 10-19 years old are of 4,263 and 8,024 individuals, respectively. Information on children or adolescents was gathered with a data collection app, and a rapid point-of-case test for SARS-CoV-2 was conducted on a finger prick blood sample., Results: The adjusted prevalence of antibodies was 2.9% (2.2-3.6) among children 0-9 years, 2.2% (1.8-2.6) among adolescents 10-19 years, and 3.0% (2.7-3.3) among adults 20+years. Prevalence of antibodies was higher among poor children and adolescents compared to those of rich families. Adherence to social distancing measures was seen in 72.4% (71.9-73.8) of families with children, 60.8% (59.6-61.9) for adolescents, and 57.4% (56.9-57.8) for adults. For not leaving the house except for essential matters the proportions were 81.7% (80.5-82.9), 70.6% (69.6-61.9), and 65.1% (64.7-65.5), respectively. Among children and adolescents, social distancing was strongly associated with socioeconomic status, being much higher in the better-off families., Conclusions: The prevalence of antibodies against SARS-CoV-2 showed comparable levels among children, adolescents, and adults. Adherence to social distancing measures was more prevalent in children, followed by adolescents. There were important socioeconomic differences in the adherence to social distancing among children and adolescents.

Since the beginning of the pandemic of COVID-19, there has been a widespread assumption that most infected persons are asymptomatic. Using data from the recent wave of the EPICOVID19 study, a nationwide household-based survey including 133 cities from all states of Brazil, we estimated the proportion of people with and without antibodies for SARS-CoV-2 who were asymptomatic, which symptoms were most frequently reported, number of symptoms and the association with socio-demographic characteristics. We tested 33,205 subjects using a rapid antibody test previously validated. Information was collected before participants received the test result. Out of 849 (2.7%) participants positive for SARS-CoV-2 antibodies, only 12.1% (95% CI 10.1-14.5) reported no symptoms, compared to 42.2% (95% CI 41.7-42.8) among those negative. The largest difference between the two groups was observed for changes in smell/taste (56.5% versus 9.1%, a 6.2-fold difference). Changes in smell/taste, fever and body aches were most likely to predict positive tests as suggested by recursive partitioning tree analysis. Among individuals without any of these three symptoms, only 0.8% tested positive, compared to 18.3% of those with both fever and changes in smell or taste. Most subjects with antibodies against SARS-CoV-2 are symptomatic, even though most present only mild symptoms.

Introduction: There is widespread concern that disruption to health services during the COVID-19 pandemic has led to declines in immunization coverage among young children, but there is limited information on the magnitude of such impact. High immunization coverage is essential for reducing the risk of vaccine preventable diseases., Methods: We used data from two nationwide sources covering the whole of Brazil. Data from the Information System of the National Immunization Program (SIPNI) on the monthly number of vaccine doses administered to young children were analyzed. The second source was a survey in 133 large cities in the 27 states in the country, carried out from August 24-27. Respondents answered a question on whether children under the age of three years had missed any scheduled vaccinations during the pandemic, and available vaccination cards were photographed for later examination., Results: SIPNI data showed that, relative to January and February 2020, there was a decline of about 20% in vaccines administered to children aged two months or older during March and April, when social distancing was at the highest level in the country. After May, vaccination levels returned to pre-pandemic values. Survey data, based on the interviews and on examination of the vaccine cards, showed that 19.0% (95% CI 17.0;21.1%) and 20.6% (95% CI 19.0;23.1%) of children, respectively, had missed immunizations. Missed doses were most common in the North (Amazon) region and least common in the South and Southeast, and also more common among children from poor than from wealthy families., Interpretation: Our results show that the pandemic was associated with a reduction of about 20% in child vaccinations, but this was reverted in recent months. Children from poor families and from the least developed regions of the country were most affected. There is an urgent need to booster immunization activities in the country to compensate for missed doses, and to reduce geographic and socioeconomic inequalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Describing the prevalence of chronic diseases and associated socioeconomic and demographic factors, evaluating the patterns of social distancing and the antibodies prevalence against SARS-CoV-2 and COVID-19 symptoms in carriers and non-carriers of chronic diseases., Methods: Data from 77,075 individuals aged 20 to 59 from three steps of the EPICOVID-19 Brazil (a nationwide serological survey conducted between May and June, 2021) were assessed. The presence of antibodies against SARS-CoV-2 was examined by rapid tests. Self-reported prevalence of hypertension, diabetes, asthma, cancer, chronic kidney disease and heart disease were investigated. The prevalence of mask use, adherence to isolation measures and antibodies were evaluated separately amid carriers and non-carriers of chronic diseases. The prevalence of symptoms was analyzed among carriers and non-carriers of chronic diseases with antibodies., Results: The prevalence of at least one chronic disease was 43%, higher in the Southeast region, among white and indigenous individuals, women, less schooled and in lower socioeconomic position. The use of masks when leaving home was similar among carriers and non-carriers of chronic diseases (98%). The proportion of participants who reported adherence to isolation measures was higher amid carriers (15.9%) than non-carriers (24.9%) of chronic diseases. The prevalence of antibodies to SARS-CoV-2 was similar amongst carriers and non-carriers (2.4% and 2.3%). The prevalence of cough, dyspnea, palpitations and myalgia was significantly higher among carriers, but the proportion of symptomatic patients was similar between groups., Conclusion: The prevalence of chronic diseases in Brazil is high and the COVID-19 pandemic affects carriers and non-carriers of chronic diseases similarly. Carriers present more severe forms of COVID-19 and higher prevalence of symptoms. Greater adherence to social distancing measures among chronic patients is disassociated from a lower incidence of COVID-19 in this group.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10 -8 ). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10 -8 ), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Objective: We aimed at evaluating the association of maternal pre-pregnancy nutritional status with offspring anthropometry and body composition. We also evaluated whether these associations were modified by gender, diet and physical activity and mediated by birth weight., Design: Birth cohort study., Setting: Waist circumference was measured with an inextensible tape, and fat and lean mass were measured using dual-energy X-ray absorptiometry. Multiple linear regression was used to adjust for possible confounders and allele score of BMI. We carried out mediation analysis using G-formula., Participants: In 1982, 1993 and 2004, all maternity hospitals in Pelotas (South Brazil) were visited daily and all live births whose families lived in the urban area of the city were evaluated. These subjects have been followed up at different ages., Results: Offspring of obese mothers had on average higher BMI, waist circumference and fat mass index than those of normal weight mothers, and these differences were higher among daughters. The magnitudes of the association were similar in the cohorts, except for height, where the association pattern was not clear. In the 1982 cohort, further adjustment for a BMI allele score had no material influence on the magnitude of the associations. Mediation analyses showed that birth weight captured part of this association., Conclusions: Our findings suggest that maternal pre-pregnancy nutritional status is positively associated with offspring BMI and adiposity in offspring. And this association is higher among daughters whose mother was overweight or obese and, birth weight explains part of this association.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response ( PLCL2 ), synaptic function and neurotransmission ( LIN7A, PFIA2 ), as well as genes previously implicated in neuropsychiatric or stress-related disorders ( FSTL5, CHODL ). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations., Competing Interests: Declaration of interest The authors declare no conflict of interests.

Background: Population-based data on COVID-19 are essential for guiding policies. There are few such studies, particularly from low or middle-income countries. Brazil is currently a hotspot for COVID-19 globally. We aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence by city and according to sex, age, ethnicity group, and socioeconomic status, and compare seroprevalence estimates with official statistics on deaths and cases., Methods: In this repeated cross-sectional study, we did two seroprevalence surveys in 133 sentinel cities in all Brazilian states. We randomly selected households and randomly selected one individual from all household members. We excluded children younger than 1 year. Presence of antibodies against SARS-CoV-2 was assessed using a lateral flow point-of-care test, the WONDFO SARS-CoV-2 Antibody Test (Wondfo Biotech, Guangzhou, China), using two drops of blood from finger prick samples. This lateral-flow assay detects IgG and IgM isotypes that are specific to the SARS-CoV-2 receptor binding domain of the spike protein. Participants also answered short questionnaires on sociodemographic information (sex, age, education, ethnicity, household size, and household assets) and compliance with physical distancing measures., Findings: We included 25 025 participants in the first survey (May 14-21) and 31 165 in the second (June 4-7). For the 83 (62%) cities with sample sizes of more than 200 participants in both surveys, the pooled seroprevalence increased from 1·9% (95% CI 1·7-2·1) to 3·1% (2·8-3·4). City-level prevalence ranged from 0% to 25·4% in both surveys. 11 (69%) of 16 cities with prevalence above 2·0% in the first survey were located in a stretch along a 2000 km of the Amazon river in the northern region. In the second survey, we found 34 cities with prevalence above 2·0%, which included the same 11 Amazon cities plus 14 from the northeast region, where prevalence was increasing rapidly. Prevalence levels were lower in the south and centre-west, and intermediate in the southeast, where the highest level was found in Rio de Janeiro (7·5% [4·2-12·2]). In the second survey, prevalence was similar in men and women, but an increased prevalence was observed in participants aged 20-59 years and those living in crowded conditions (4·4% [3·5-5·6] for those living with households with six or more people). Prevalence among Indigenous people was 6·4% (4·1-9·4) compared with 1·4% (1·2-1·7) among White people. Prevalence in the poorest socioeconomic quintile was 3·7% (3·2-4·3) compared with 1·7% (1·4-2·2) in the wealthiest quintile., Interpretation: Antibody prevalence was highly heterogeneous by country region, with rapid initial escalation in Brazil's north and northeast. Prevalence is strongly associated with Indigenous ancestry and low socioeconomic status. These population subgroups are unlikely to be protected if the policy response to the pandemic by the national government continues to downplay scientific evidence., Funding: Brazilian Ministry of Health, Instituto Serrapilheira, Brazilian Collective Health Association, and the JBS Fazer o Bem Faz Bem., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Breastfeeding is associated with short and long-term health benefits. Long-term effects might be mediated by epigenetic mechanisms, yet the literature on this topic is scarce. We performed the first epigenome-wide association study of infant feeding, comparing breastfed vs non-breastfed children. We measured DNA methylation in children from peripheral blood collected in childhood (age 7 years, N = 640) and adolescence (age 15-17 years, N = 709) within the Accessible Resource for Integrated Epigenomic Studies (ARIES) project, part of the larger Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Cord blood methylation (N = 702) was used as a negative control for potential pre-natal residual confounding., Results: Two differentially-methylated sites presented directionally-consistent associations with breastfeeding at ages 7 and 15-17 years, but not at birth. Twelve differentially-methylated regions in relation to breastfeeding were identified, and for three of them there was evidence of directional concordance between ages 7 and 15-17 years, but not between birth and age 7 years., Conclusions: Our findings indicate that DNA methylation in childhood and adolescence may be predicted by breastfeeding, but further studies with sufficiently large samples for replication are required to identify robust associations.

Objectives: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil., Methods: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses., Results: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant., Conclusions: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

During ejaculation, a large amount of seminal plasma proteins interact with the sperm membrane, leading to a series of biochemical and structural changes implicated in sperm function and gamete interaction. However, the roles of the majority of these proteins remain unknown. This study aimed to investigate the proteome and functionality of the major equine proteins of seminal plasma and the sperm membrane. Seminal plasma and enriched-membrane proteins (150 μg) were separated by two-dimensional gel electrophoresis, and the respective maps were analyzed. Protein identification was performed by in-gel digestion and tandem mass spectrometry (GeLC-MS/MS). Samples were also submitted to in-solution digestion (complex protein mixture) and identified by shotgun analysis by LC-MS/MS; bioinformatic tools were used to investigate protein functions. Seminal plasma and sperm membrane extract maps contained 91.0 ± 8.2 spots and 245.3 ± 11.3 spots, respectively, within the 3-10 pH range. In total, the most abundant proteins identified in 2D maps and in complex protein mixtures included 24 proteins for seminal plasma and 33 for sperm membrane extract, with a high degree of confidence (P < 0.05). Of these, HSP1, CRISP3 and KLK1E2 were the most abundant in seminal plasma; HSP1 was highly abundant in sperm membrane extract, in many isoforms, which is related to membrane destabilization and may compromise sperm preservation. HSP1-polybromo-1 interactions suggested a role in DNA stabilization. Prosaposin was identified in seminal plasma and may play a role in the fertilization process. IZUMO4, a member of the IgSF family involved in the prefertilization stages, was identified in 2D gel and MS/MS analysis of sperm membrane extract. Ten proteins of seminal plasma were found to interact with the sperm membrane and were related to binding and catalytic activities (clusterin, CRISP3, epididymal sperm-binding protein 1, kallikrein1E2, seminal plasma protein A3, and HSP1). Additionally, other identified proteins were associated with DNA integrity, capacitation and recognition of pregnancy. These findings indicate that the binding of specific proteins to the plasma membrane during ejaculation may influence sperm survival after cryopreservation and may play a role in decreasing the quality in stallions with toxic seminal plasma. Elucidation of these interactions is an important step in understanding the biological processes related to equine fertility and facilitates future investigations on the selection and application of low freezability semen strategies., Competing Interests: Declaration of competing interest The authors state that they have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Geospatial approaches are increasingly used to produce fine spatial scale estimates of reproductive, maternal, newborn and child health (RMNCH) indicators in low- and middle-income countries (LMICs). This study aims to describe important methodological aspects and specificities of geospatial approaches applied to RMNCH coverage and impact outcomes and enable non-specialist readers to critically evaluate and interpret these studies., Methods: Two independent searches were carried out using Medline, Web of Science, Scopus, SCIELO and LILACS electronic databases. Studies based on survey data using geospatial approaches on RMNCH in LMICs were considered eligible. Studies whose outcomes were not measures of occurrence were excluded., Results: We identified 82 studies focused on over 30 different RMNCH outcomes. Bayesian hierarchical models were the predominant modeling approach found in 62 studies. 5 × 5 km estimates were the most common resolution and the main source of information was Demographic and Health Surveys. Model validation was under reported, with the out-of-sample method being reported in only 56% of the studies and 13% of the studies did not present a single validation metric. Uncertainty assessment and reporting lacked standardization, and more than a quarter of the studies failed to report any uncertainty measure., Conclusions: The field of geospatial estimation focused on RMNCH outcomes is clearly expanding. However, despite the adoption of a standardized conceptual modeling framework for generating finer spatial scale estimates, methodological aspects such as model validation and uncertainty demand further attention as they are both essential in assisting the reader to evaluate the estimates that are being presented.

Background: Studies on mental disorders prevalence and comorbidity, including suicidality, are scarce in low and middle-income settings. We aimed to describe the pattern of comorbidity between mental disorders and their association with suicidality., Methods: In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified (n = 5914) and have been prospectively followed. Participants were evaluated for the presence of common mental disorders (CMD) at the ages of 18-19, 23 and 30 years. In 2012-13 (30 years of age), trained psychologists evaluated 3657 individuals for disorders using the Mini International Neuropsychiatric Interview., Results: Prevalence of suicidal wishing, suicidal planning and lifetime suicidal attempt was 4.9%, 3.8% and 6.6%, respectively. Suicidal wishing was most strongly associated with having joint major depressive episode (MD) and lifetime suicidal attempt (OR = 26.4, 95%CI:13.9-50.4) with comorbid MD with mania/hypomania (OR = 21.2, 95%CI:6.93-65.1). Suicidal planning was most strongly associated with having joint MD and lifetime suicidal attempt (OR = 44.7, 95%CI:22.6-88.4), with comorbid MD and social anxiety disorder (OR = 30.6, 95%CI:13.0-72.0), and joint social anxiety disorder with lifetime suicidal attempt (OR = 26.3, 95%CI:8.33-82.7). Independently of other disorders, prospective and cross-sectional measures of CMD were associated with higher rates of suicidality., Limitations: We do not have data on suicide deaths in follow-up and the diagnostic instrument used at 30 years of age was not used in all previous follow-up., Conclusion: MD and social anxiety have independent and combined associations with suicidality, and also with they occur with lifetime suicidal attempt and other mental disorders., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020. Published by Elsevier Inc.)