Average Causal Effect Estimation Via Instrumental Variables: the No Simultaneous Heterogeneity Assumption.

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.

Homogeneity in the Instrument-exposure Association and Point Estimation Using Binary Instrumental Variables.

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.

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

Influence of maternal pre-pregnancy nutritional status on offspring anthropometric measurements and body composition in three Brazilian Birth Cohorts.

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.

Mental disorders, comorbidities, and suicidality at 30 years of age in a Brazilian birth cohort.

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.

Bias in Mendelian randomization due to assortative mating.

Mendelian randomization (MR) has been increasingly used to strengthen causal inference in observational epidemiology. Methodological developments in the field allow detecting and/or adjusting for different potential sources of bias, mainly bias due to horizontal pleiotropy (or "off-target" genetic effects). Another potential source of bias is nonrandom matching between spouses (i.e., assortative mating). In this study, we performed simulations to investigate the bias caused in MR by assortative mating. We found that bias can arise due to either cross-trait assortative mating (i.e., assortment on two phenotypes, such as highly educated women selecting taller men) or single-trait assortative mating (i.e., assortment on a single phenotype), even if the exposure and outcome phenotypes are not the phenotypes under assortment. The simulations also indicate that bias due to assortative mating accumulates over generations and that MR methods robust to horizontal pleiotropy are also affected by this bias. Finally, we show that genetic data from mother-father-offspring trios can be used to detect and correct for this bias.

Assessing causality in the association between attention-deficit/hyperactivity disorder and obesity: a Mendelian randomization study.

BACKGROUND/OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood and adolescence, is associated with obesity in observational studies. However, it is unclear whether ADHD contributes to, results from or is merely correlated with obesity. This study evaluates the presence and direction of a causal effect between ADHD and obesity. SUBJECTS/METHODS: We performed a bidirectional two-sample Mendelian randomization using summary data from consortia of genome-wide association studies to investigate if ADHD (N = 55,374) has a causal effect on body mass index (BMI) in childhood (N = 35,668) and adulthood (N = 322,154-500,000), and vice-versa. The main analysis was performed using the inverse variance weighted (IVW) method. As sensitivity analyses, we used other Mendelian randomization methods that are more robust to horizontal pleiotropy (i.e., MR-Egger, weighted mode, and penalized weighted median estimators), as well as stratified the analysis by the putative mechanisms of genetic instruments (i.e., pathways involved or not in neurological processes). RESULTS: The IVW method indicated a positive causal effect of BMI on ADHD: ß = 0.324 (95% CI 0.198 to 0.449, p < 0.001; expressed as change in ln(odds ratio) of ADHD per each additional SD unit of BMI). IVW estimates were directionally consistent with other methods. On the other hand, we did not find consistent evidence for a causal effect of ADHD genetic liability on BMI. CONCLUSIONS: The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Genomic ancestry and the social pathways leading to major depression in adulthood: the mediating effect of socioeconomic position and discrimination.

BACKGROUND: Evidence suggests that there is an association between ethnicity/skin color and depression; however, many contextual and individual variables, like sense of discrimination and socioeconomic position (SEP), might influence the direction of this association. We assessed the association between African ancestry and major depression among young adults that have been followed-up since birth in a Southern Brazilian city, and the mediating effect of SEP and discrimination. METHODS: In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n = 5914). In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for major depression diagnosis. In addition, DNA samples were genotyped for approximately 2.5 million single nucleotide polymorphisms (SNPs) using Illumina (CA, USA) HumanOmni2.5-8v1 array. Genomic ancestry estimation was based on approximately 370 000 single nucleotide polymorphisms (SNPs) mutually available for the Pelotas cohort and selected samples (used as reference panels) of the HapMap and Human Genome Diversity (HGDP). We estimated prevalence ratios (PR) using Poisson regression models and evaluated the association between percentage of African ancestry and major depression. We used G-computation for mediation analysis. RESULTS: At 30 years, 3576 individuals were evaluated for major depression (prevalence = 7.9 %). Only individuals in the highest SEP, who had a percentage of African ancestry between >5-30 % and >30 % had a prevalence of major depression 2.16 (PR = 2.16 95 % CI [1.05-4.45]) and 2.74 (PR = 2.74 95 % CI [1.06-7.06]) times higher, than those with 5 % or less, respectively. Among these subjects, sense of discrimination by skin color, captured 84 % of the association between African ancestry and major depression. CONCLUSION: SEP is an important effect modifier of the positive association between African ancestry and major depression. In addition, this association is predominantly mediated by the sense of feeling discriminated by skin color.

The effects of a large-scale home visiting programme for child development on use of health services in Brazil.

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.

Towards a better understanding of real-world home-visiting programs: a large-scale effectiveness study of parenting mechanisms in Brazil.

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 (ß=0.08, 95% CIs 0.002 to 0.16) and sensitivity (ß=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 (ß=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.

Maternal mental health and offspring's IQ: Evidence from two Brazilian birth cohorts.

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.

Effectiveness of a large-scale home visiting programme (PIM) on early child development in Brazil: quasi-experimental study nested in a birth cohort.

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.

Interaction-based Mendelian randomization with measured and unmeasured gene-by-covariate interactions.

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.

Bias in two-sample Mendelian randomization when using heritable covariable-adjusted summary associations.

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.

Chronic non-communicable diseases and COVID-19: EPICOVID-19 Brazil results.

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.

Association between cesarean section and human capital in adulthood: 1982 and 1993 Pelotas birth cohorts, Rio Grande do Sul State, Brazil.

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.

Influenza vaccination in older adults during the COVID-19 pandemic: a population-based study in 133 Brazilian cities. / Vacinação para influenza em idosos na pandemia COVID-19: estudo de base populacional em 133 cidades brasileiras.

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.

Imunizações de rotina durante pandemias podem ser prejudicadas. Este estudo estimou a cobertura vacinal para influenza em idosos durante a COVID-19 através do EPICOVID-19, inquérito populacional realizado em 133 cidades sentinelas dos 26 estados brasileiros e Distrito Federal. Selecionou-se 25 setores censitários por cidade, amostragem proporcional ao tamanho, dez domicílios por setor e uma pessoa por domicílio, aleatoriamente. O quantitativo de 8.265 idosos (≥ 60 anos) foram entrevistados e responderam se haviam sido vacinados contra gripe em 2020. A cobertura foi 82,3% (IC95% 80,1; 84,2), sem diferenças por sexo, idade ou região. Maiores coberturas ocorreram nos mais ricos (84,7% versus 80,1% nos mais pobres) e nos mais escolarizados (87,3% versus 83,2% nos menos escolarizados). Menor cobertura nos indígenas (56,9% versus coberturas superiores a 80% nos demais grupos étnicos). Houve associação positiva com número de comorbidades entre homens, mas não entre mulheres. A maioria vacinou-se na rede pública (97,5%), sendo a rede privada mais utilizada na região Sul, pelos mais escolarizados e mais ricos. Conclui-se que a cobertura vacinal ficou sete pontos percentuais abaixo da meta governamental (90%), e que desigualdades devem ser revertidas em futuras campanhas.