Early-life socioeconomic circumstances and the comorbidity of depression and overweight in adolescence and young adulthood: A prospective study.

Depression and overweight both often emerge early in life and have been found to be associated, but few studies examine depression-overweight comorbidity and its social patterning early in the life course. Drawing on data from 4,948 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort from the UK (2,798 female, 2,150 male), we investigated how different aspects of early-life socioeconomic circumstances are associated with depression-overweight comorbidity from adolescence to young adulthood exploring any differences by age and sex. We estimated how parental education, social class and financial difficulties reported in pregnancy were associated with depression and overweight, and their comorbidity at approximately the ages 17 and 24 in males and females. The results from multinomial logistic regression models showed that all three socioeconomic markers were associated with depression-overweight comorbidity and results were similar across age. Lower parental education (relative risk ratio (RRR) and 95% confidence interval (CI) of low education v high education: 3.61 (2.30-5.67) in females and 1.54 (1.14-2.07) in males) and social class (class IV/V v class I: 5.67 (2.48-12.94) in females and 3.11 (0.70-13.91) in males) had strong associations with comorbidity at age 17 relative to having neither depression or overweight. Financial difficulties were also a risk factor in females, with less clear results in males. These findings highlight how early socioeconomic circumstances are linked with the accumulation of mental and physical health problems already in adolescence, which has implications for life-long health inequalities.

Time-sensitive testing pressures and COVID-19 outcomes: are socioeconomic inequalities over the first year of the pandemic explained by selection bias?

BACKGROUND: There are many ways in which selection bias might impact COVID-19 research. Here we focus on selection for receiving a polymerase-chain-reaction (PCR) SARS-CoV-2 test and how known changes to selection pressures over time may bias research into COVID-19 infection. METHODS: Using UK Biobank (N = 420,231; 55% female; mean age = 66.8 [SD = 8·11]) we estimate the association between socio-economic position (SEP) and (i) being tested for SARS-CoV-2 infection versus not being tested (ii) testing positive for SARS-CoV-2 infection versus testing negative and (iii) testing negative for SARS-CoV-2 infection versus not being tested. We construct four distinct time-periods between March 2020 and March 2021, representing distinct periods of testing pressures and lockdown restrictions and specify both time-stratified and combined models for each outcome. We explore potential selection bias by examining associations with positive and negative control exposures. RESULTS: The association between more disadvantaged SEP and receiving a SARS-CoV-2 test attenuated over time. Compared to individuals with a degree, individuals whose highest educational qualification was a GCSE or equivalent had an OR of 1·27 (95% CI: 1·18 to 1·37) in March-May 2020 and 1·13 (95% CI: 1.·10 to 1·16) in January-March 2021. The magnitude of the association between educational attainment and testing positive for SARS-CoV-2 infection increased over the same period. For the equivalent comparison, the OR for testing positive increased from 1·25 (95% CI: 1·04 to 1·47), to 1·69 (95% CI: 1·55 to 1·83). We found little evidence of an association between control exposures, and any considered outcome. CONCLUSIONS: The association between SEP and SARS-CoV-2 testing changed over time, highlighting the potential of time-specific selection pressures to bias analyses of COVID-19. Positive and negative control analyses suggest that changes in the association between SEP and SARS-CoV-2 infection over time likely reflect true increases in socioeconomic inequalities.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Continuing inequalities in COVID-19 mortality in England and Wales, and the changing importance of regional, over local, deprivation.

BACKGROUND: Observational studies have highlighted that where individuals live is far more important for risk of dying with COVID-19, than for dying of other causes. Deprivation is commonly proposed as explaining such differences. During the period of localised restrictions in late 2020, areas with higher restrictions tended to be more deprived. We explore how this impacted the relationship between deprivation and mortality and see whether local or regional deprivation matters more for inequalities in COVID-19 mortality. METHODS: We use publicly available population data on deaths due to COVID-19 and all-cause mortality between March 2020 and April 2021 to investigate the scale of spatial inequalities. We use a multiscale approach to simultaneously consider three spatial scales through which processes driving inequalities may act. We go on to explore whether deprivation explains such inequalities. RESULTS: Adjusting for population age structure and number of care homes, we find highest regional inequality in October 2020, with a COVID-19 mortality rate ratio of 5.86 (95% CI 3.31 to 19.00) for the median between-region comparison. We find spatial context is most important, and spatial inequalities higher, during periods of low mortality. Almost all unexplained spatial inequality in October 2020 is removed by adjusting for deprivation. During October 2020, one standard deviation increase in regional deprivation was associated with 20% higher local mortality (95% CI, 1.10 to 1.30). CONCLUSIONS: Spatial inequalities are greatest in periods of lowest overall mortality, implying that as mortality declines it does not do so equally. During the prolonged period of low restrictions and low mortality in summer 2020, spatial inequalities strongly increased. Contrary to previous months, we show that the strong spatial patterning during autumn 2020 is almost entirely explained by deprivation. As overall mortality declines, policymakers must be proactive in detecting areas where this is not happening, or risk worsening already strong health inequalities.

Cross-sectional analysis of educational inequalities in primary prevention statin use in UK Biobank.

OBJECTIVE: Identify whether participants with lower education are less likely to report taking statins for primary cardiovascular prevention than those with higher education, but an equivalent increase in underlying cardiovascular risk. METHODS: Using data from a large prospective cohort study, UK Biobank, we calculated a QRISK3 cardiovascular risk score for 472 097 eligible participants with complete data on self-reported educational attainment and statin use (55% female participants; mean age 56 years). We used logistic regression to explore the association between (i) QRISK3 score and (ii) educational attainment on self-reported statin use. We then stratified the association between QRISK3 score and statin use, by educational attainment to test for interactions. RESULTS: There was evidence of an interaction between QRISK3 score and educational attainment. Per unit increase in QRISK3 score, more educated individuals were more likely to report taking statins. In women with ≤7 years of schooling, a one unit increase in QRISK3 score was associated with a 7% higher odds of statin use (OR 1.07, 95% CI 1.07 to 1.07). In women with ≥20 years of schooling, a one unit increase in QRISK3 score was associated with an 14% higher odds of statin use (OR 1.14, 95% CI 1.14 to 1.15). Comparable ORs in men were 1.04 (95% CI 1.04 to 1.05) for ≤7 years of schooling and 1.08 (95% CI 1.08, 1.08) for ≥20 years of schooling. CONCLUSION: Per unit increase in QRISK3 score, individuals with lower educational attainment were less likely to report using statins, likely contributing to health inequalities.

Long-term cost-effectiveness of interventions for obesity: A mendelian randomisation study.

BACKGROUND: The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and determining healthcare funding. Current methods for estimating cost-effectiveness of interventions for obesity may be subject to confounding and reverse causation. The aim of this study is to apply a new approach using mendelian randomisation for estimating the cost-effectiveness of interventions that target body mass index (BMI), which may be less affected by confounding and reverse causation than previous approaches. METHODS AND FINDINGS: We estimated health-related quality-adjusted life years (QALYs) and both primary and secondary healthcare costs for 310,913 men and women of white British ancestry aged between 39 and 72 years in UK Biobank between recruitment (2006 to 2010) and 31 March 2017. We then estimated the causal effect of differences in BMI on QALYs and total healthcare costs using mendelian randomisation. For this, we used instrumental variable regression with a polygenic risk score (PRS) for BMI, derived using a genome-wide association study (GWAS) of BMI, with age, sex, recruitment centre, and 40 genetic principal components as covariables to estimate the effect of a unit increase in BMI on QALYs and total healthcare costs. Finally, we used simulations to estimate the likely effect on BMI of policy relevant interventions for BMI, then used the mendelian randomisation estimates to estimate the cost-effectiveness of these interventions. A unit increase in BMI decreased QALYs by 0.65% of a QALY (95% confidence interval [CI]: 0.49% to 0.81%) per year and increased annual total healthcare costs by £42.23 (95% CI: £32.95 to £51.51) per person. When considering only health conditions usually considered in previous cost-effectiveness modelling studies (cancer, cardiovascular disease, cerebrovascular disease, and type 2 diabetes), we estimated that a unit increase in BMI decreased QALYs by only 0.16% of a QALY (95% CI: 0.10% to 0.22%) per year. We estimated that both laparoscopic bariatric surgery among individuals with BMI greater than 35 kg/m2, and restricting volume promotions for high fat, salt, and sugar products, would increase QALYs and decrease total healthcare costs, with net monetary benefits (at £20,000 per QALY) of £13,936 (95% CI: £8,112 to £20,658) per person over 20 years, and £546 million (95% CI: £435 million to £671 million) in total per year, respectively. The main limitations of this approach are that mendelian randomisation relies on assumptions that cannot be proven, including the absence of directional pleiotropy, and that genotypes are independent of confounders. CONCLUSIONS: Mendelian randomisation can be used to estimate the impact of interventions on quality of life and healthcare costs. We observed that the effect of increasing BMI on health-related quality of life is much larger when accounting for 240 chronic health conditions, compared with only a limited selection. This means that previous cost-effectiveness studies have likely underestimated the effect of BMI on quality of life and, therefore, the potential cost-effectiveness of interventions to reduce BMI.

Early adulthood socioeconomic trajectories contribute to inequalities in adult cardiovascular health, independently of childhood and adulthood socioeconomic position.

BACKGROUND: Cardiovascular health shows significant socioeconomic inequalities, however there is little understanding of the role of early adulthood in generation of these inequalities. We assessed the contribution of socioeconomic trajectories during early adulthood (16-24 years) to cardiovascular health in mid-adulthood (46 years). METHODS: Participants from the 1970 British Cohort Study with socioeconomic data available in early adulthood were included (n=12 423). Longitudinal latent class analysis identified socioeconomic trajectories, based on patterns of economic activity throughout early adulthood. Cardiometabolic risk factors (46 years) were regressed on socioeconomic trajectory class (16-24 years), testing mediation by adult socioeconomic position (46 years). Models were stratified by sex and adjusted for childhood socioeconomic position (SEP) and adolescent health. RESULTS: Six early adulthood socioeconomic trajectories were identified: (1) Continued Education (20.2%), (2) Managerial Employment (16.0%), (3) Skilled Non-manual Employment (20.9%), (4) Skilled Manual Employment (18.9%), (5) Partly Skilled Employment (15.8%) and (6) Economically Inactive (8.1%). The 'Continued Education' trajectory class showed the best cardiovascular health at age 46 years, with the lowest levels of cardiometabolic risk factors. For example, systolic blood pressure was 128.9 mm Hg (95% CI 127.8 to 130.0) among men in the 'Continued Education' class, compared with 131.3 mm Hg (95% CI 130.4 to 132.2) among men in the 'Skilled Manual' class. Patterns across classes 2-6 differed by risk factor and sex. The observed associations were largely not mediated by SEP at age 46 years. CONCLUSION: Findings suggest an independent contribution of early adulthood socioeconomic trajectories to development of later life cardiovascular inequalities. Further work is needed to understand mediators of this relationship and potential for interventions to mitigate these pathways.

Interrogating structural inequalities in COVID-19 mortality in England and Wales.

BACKGROUND: Numerous observational studies have highlighted structural inequalities in COVID-19 mortality in the UK. Such studies often fail to consider the hierarchical, spatial nature of such inequalities in their analysis, leading to the potential for bias and an inability to reach conclusions about the most appropriate structural levels for policy intervention. METHODS: We use publicly available population data on COVID-19-related mortality and all-cause mortality between March and July 2020 in England and Wales to investigate the spatial scale of such inequalities. We propose a multiscale approach to simultaneously consider three spatial scales at which processes driving inequality may act and apportion inequality between these. RESULTS: Adjusting for population age structure and number of local care homes we find highest regional inequality in March and June/July. We find finer grained within region inequality increased steadily from March until July. The importance of spatial context increases over the study period. No analogous pattern is visible for non-COVID-19 mortality. Higher relative deprivation is associated with increased COVID-19 mortality at all stages of the pandemic but does not explain structural inequalities. CONCLUSIONS: Results support initial stochastic viral introduction in the South, with initially high inequality decreasing before the establishment of regional trends by June and July, prior to reported regionality of the 'second-wave'. We outline how this framework can help identify structural factors driving such processes, and offer suggestions for a long-term, locally targeted model of pandemic relief in tandem with regional support to buffer the social context of the area.

Metabolic profiles of socio-economic position: a multi-cohort analysis.

BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. CONCLUSIONS: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Associations of adverse childhood experiences with educational attainment and adolescent health and the role of family and socioeconomic factors: A prospective cohort study in the UK.

BACKGROUND: Experiencing multiple adverse childhood experiences (ACEs) is a risk factor for many adverse outcomes. We explore associations of ACEs with educational attainment and adolescent health and the role of family and socioeconomic factors in these associations. METHODS AND FINDINGS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective cohort of children born in southwest England in 1991-1992, we assess associations of ACEs between birth and 16 years (sexual, physical, or emotional abuse; emotional neglect; parental substance abuse; parental mental illness or suicide attempt; violence between parents; parental separation; bullying; and parental criminal conviction, with data collected on multiple occasions between birth and age 16) with educational attainment at 16 years (n = 9,959) and health at age 17 years (depression, obesity, harmful alcohol use, smoking, and illicit drug use; n = 4,917). We explore the extent to which associations are robust to adjustment for family and socioeconomic factors (home ownership, mother and partner's highest educational qualification, household social class, parity, child's ethnicity, mother's age, mother's marital status, mother's depression score at 18 and 32 weeks gestation, and mother's partner's depression score at 18 weeks gestation) and whether associations differ according to socioeconomic factors, and we estimate the proportion of adverse educational and health outcomes attributable to ACEs or family or socioeconomic measures. Among the 9,959 participants (49.5% female) included in analysis of educational outcomes, 84% reported at least one ACE, 24% reported 4 or more ACEs, and 54.5% received 5 or more General Certificates of Secondary Education (GCSEs) at grade C or above, including English and Maths. Among the 4,917 participants (50.1% female) included in analysis of health outcomes, 7.3% were obese, 8.7% had depression, 19.5% reported smoking, 16.1% reported drug use, and 10.9% reported harmful alcohol use. There were associations of ACEs with lower educational attainment and higher risk of depression, drug use, and smoking. For example, odds ratios (ORs) for 4+ ACEs compared with no ACEs after adjustment for confounders were depression, 2.4 (1.6-3.8, p < 0.001); drug use, 3.1 (2.1-4.4, p < 0.001); and smoking, 2.3 (1.7-3.1, p < 0.001). Associations with educational attainment attenuated after adjustment but remained strong; for example, the OR after adjustment for confounders for low educational attainment comparing 4+ ACEs with no ACEs was 2.0 (1.7-2.4, p < 0.001). Associations with depression, drug use, and smoking were not altered by adjustment. Associations of ACEs with harmful alcohol use and obesity were weak. For example, ORs for 4+ ACEs compared with no ACEs after adjustment for confounders were harmful alcohol use, 1.4 (0.9-2.0, p = 0.10) and obesity, 1.4 (0.9-2.2, p = 0.13) We found no evidence that socioeconomic factors modified the associations of ACEs with educational or health outcomes. Population attributable fractions (PAFs) for the adverse educational and health outcomes range from 5%-15% for 4+ ACEs and 1%-19% for low maternal education. Using data from multiple questionnaires across a long period of time enabled us to capture a detailed picture of the cohort members' experience of ACEs; however, a limitation of our study is that this resulted in a high proportion of missing data, and our analyses assume data are missing at random. CONCLUSIONS: This study demonstrates associations between ACEs and lower educational attainment and higher risks of depression, drug use, and smoking that remain after adjustment for family and socioeconomic factors. The low PAFs for both ACEs and socioeconomic factors imply that interventions that focus solely on ACEs or solely on socioeconomic deprivation, whilst beneficial, would miss most cases of adverse educational and health outcomes. This interpretation suggests that intervention strategies should target a wide range of relevant factors, including ACEs, socioeconomic deprivation, parental substance use, and mental health.

Effects of body mass index on relationship status, social contact and socio-economic position: Mendelian randomization and within-sibling study in UK Biobank.

BACKGROUND: We assessed whether body mass index (BMI) affects social and socio-economic outcomes. METHODS: We used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank. RESULTS: In MR of minimally related individuals, higher BMI was related to higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. Non-linear MR suggested both low (bottom decile, <22 kg/m2) and high (top seven deciles, >24.6 kg/m2) BMI, increased deprivation and reduced income. Non-genetic within-sibling analysis supported an effect of BMI on socio-economic position (SEP); precision in within-sibling MR was too low to draw inference about effects of BMI on SEP. There was some evidence of pleiotropy, with MR Egger suggesting limited effects of BMI on deprivation, although precision of these estimates is also low. Non-linear MR suggested that low BMI (bottom three deciles, <23.5 kg/m2) reduces the odds of cohabiting with a partner or spouse in men, whereas high BMI (top two deciles, >30.7 kg/m2) reduces the odds of cohabitation in women. Both non-genetic and MR within-sibling analyses supported this sex-specific effect of BMI on cohabitation. In men only, higher BMI was related to lower participation in leisure and social activities. There was little evidence that BMI affects visits from friends and family or having someone to confide in. CONCLUSIONS: BMI may affect social and socio-economic outcomes, with both high and low BMI being detrimental for SEP, although larger within-family MR studies may help to test the robustness of MR results in unrelated individuals. Triangulation of evidence across MR and within-family analyses supports evidence of a sex-specific effect of BMI on cohabitation.

Socioeconomic differences in childhood BMI trajectories in Belarus.

OBJECTIVE: To examine associations of parental socioeconomic position with early-life offspring body mass index (BMI) trajectories in a middle-income country. SUBJECTS: Overall, 12,385 Belarusian children born 1996-97 and enrolled in a randomised breastfeeding promotion trial at birth, with 3-14 measurements of BMI from birth to 7 years. METHODS: Cohort analysis in which exposures were parental education (common secondary or less; advanced secondary or partial university; completed university) and occupation (manual; non-manual) at birth, and the outcome was BMI z-score trajectories estimated using multilevel linear spline models, controlling for trial arm, location, parental BMI, maternal smoking status and number of older siblings. RESULTS: Infants born to university-educated mothers were heavier at birth than those born to secondary school-educated mothers [by 0.13 BMI z-score units (95% confidence interval, CI: 0.07, 0.19) for girls and 0.11 (95% CI: 0.05, 0.17) for boys; equivalent for an infant of average birth length to 43 and 38 g, respectively]. Between the ages of 3-7 years children of the most educated mothers had larger BMI increases than children of the least educated mothers. At age 7 years, after controlling for trial arm and location,  children of university-educated mothers had higher BMIs than those born to secondary school-educated mothers by 0.11 z-score (95% CI: 0.03, 0.19) among girls and 0.18 (95% CI: 0.1, 0.27) among boys, equivalent to differences in BMI for a child of average height of 0.19 and 0.26 kg/m2, respectively. After further controlling for parental BMI, these differences attenuated to 0.08 z-score (95% CI: 0, 0.16) and 0.16 z-score (95% CI: 0.07, 0.24), respectively, but changed very little after additional adjustment for number of older siblings and mother's smoking status. Associations were similar when based on paternal educational attainment and highest household occupation. CONCLUSIONS: In Belarus, consistent with some middle-income countries, higher socioeconomic position was associated with greater BMI trajectories from age 3 onwards.

Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers.

BACKGROUND: Previous studies of childhood psychosocial adversity and age at menarche mostly evaluated single or a few measures of adversity, and therefore could not quantify total psychosocial adversity. Limited knowledge is currently available regarding childhood psychosocial adversity in relation to age at menopause and reproductive lifespan. METHODS: We examined the associations of total and specific components of childhood psychosocial adversity with age at menarche (n=8984), age at menopause (n=945), and length of reproductive lifespan (n=841), in mothers participating in the Avon Longitudinal Study of Parents and Children. We used confirmatory factor analysis to characterise lack of care, maladaptive family functioning, non-sexual abuse, overprotective parenting, parental mental illness and sexual abuse. These specific components of childhood psychosocial adversity were combined into a total psychosocial adversity score using a second-order factor analysis. We used structural equation models to simultaneously conduct the factor analysis and estimate the association with the continuous outcomes of interest. RESULTS: Total childhood psychosocial adversity was not associated with age at menarche, age at menopause or length of reproductive lifespan. When we examined the separate psychosocial adversity constructs, sexual abuse was inversely associated with age at menarche, with a mean difference of -0.17 (95% CI -0.23 to -0.12) years per SD higher factor score, and with age at menopause, with a mean difference of -0.17 (95% CI -0.52 to 0.18) per SD higher factor score. CONCLUSION: Childhood sexual abuse was associated with lower age at menarche and menopause, but the latter needs to be confirmed in larger samples.

Are objective measures of physical capability related to accelerated epigenetic age? Findings from a British birth cohort.

OBJECTIVES: Our aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality. SETTING: The MRC National Survey of Health and Development (NSHD) cohort study. PARTICIPANTS: We used data from 790 women from the NSHD who had DNA methylation data available. DESIGN: Epigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60-64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position. OUTCOME MEASURES: Three objective measures of physical capability were used: grip strength, standing balance time and chair rise speed. RESULTS: Epigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60-64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells. CONCLUSIONS: We found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60-64, but no association with standing balance time or chair rise speed was found.

Adversity in childhood and measures of aging in midlife: Findings from a cohort of british women.

Very few studies have assessed whether socioeconomic and psychosocial adversity during childhood are associated with objective measures of aging later in life. We assessed associations of socioeconomic position (SEP) and total psychosocial adversity during childhood, with objectively measured cognitive and physical capability in women during midlife. Adverse childhood experiences were retrospectively reported at mean ages 28-30 years in women from the Avon Longitudinal Study of Parents And Children (N = 2,221). We investigated associations of childhood SEP and total psychosocial adversity, with composite measures of cognitive and physical capability at mean age 51 years. There was evidence that, compared with participants whose fathers had professional occupations, participants whose fathers had managerial/technical, skilled nonmanual, skilled manual, and partly or unskilled manual occupations had, on average, lower physical and cognitive capability. There was a clear trend for increasing magnitudes of association with lowering childhood SEP. There was also evidence that greater total psychosocial adversity in childhood was associated with lower physical capability. Total psychosocial adversity in childhood was not associated with cognitive capability. Lower SEP in childhood is detrimental to cognitive and physical capability in midlife, at least in part, independently of subsequent SEP in adulthood. Greater psychosocial adversity in childhood is associated with poorer physical capability, independently of social disadvantage in childhood. Our findings highlight the need for interventions to both identify and support children experiencing socioeconomic or psychosocial of adversity as early as possible. (PsycINFO Database Record

Socioeconomic disparities in birth weight and body mass index during infancy through age 7†years: a study within the Danish National Birth Cohort.

BACKGROUND: Socioeconomic inequalities in birth weight and in body mass index (BMI) later in childhood are in opposite directions, which raises questions about when during childhood the change in direction happens. We examined how maternal and paternal education and household income were associated with birthweight z-scores and with BMI z-scores at age 5 and 12 months and 7 years, and we examined the socioeconomic differences in the tracking of these z-scores across infancy and childhood. METHODS: The associations were studied in a cohort of children in the Danish National Birth Cohort, single born between 1997 and 2003, for whom information on body size from at least 1 of 4 time points (n=85 062) was recorded. We examined the associations using linear mixed-effects modelling. RESULTS: Children from families with a low maternal and paternal educational level changed their body size z-scores upwards between birth and age 7 years. At age 5 and 12 months, there were no educational gradient. A low maternal educational level was associated with lower birth weight for gestational age z-scores at birth for boys (-0.199; 95% CI -0.230 to -0.169) and girls (-0.198; 95% CI -0.229 to -0.167) and higher BMI z-scores at age 7 for boys (0.198; 95% CI 0.154 to 0.242) and girls (0.218; 95% CI 0.173 to 0.264). There was not a similarly clear pattern in the tracking between different household income groups. However, a low household income level was associated with higher z-scores of both birth weight and BMI at age 7 years, but with a much weaker gradient at 5 and 12 months. CONCLUSIONS: The educational gradient shifts from positive with birth weight, to none during infancy to inverse with BMI at age 7 years. In contrast, the income gradient was positive at birth and at 7 years and much weaker during infancy.

Relationship between mediation analysis and the structured life course approach.

Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome).

The Relationship Between Socioeconomic Status and CV Risk Factors: The CRONICAS Cohort Study of Peruvian Adults.

BACKGROUND: Variations in the distribution of cardiovascular disease and risk factors by socioeconomic status (SES) have been described in affluent societies, yet a better understanding of these patterns is needed for most low- and middle-income countries. OBJECTIVE: This study sought to describe the relationship between cardiovascular risk factors and SES using monthly family income, educational attainment, and assets index, in 4 Peruvian sites. METHODS: Baseline data from an age- and sex-stratified random sample of participants, ages ≥35 years, from 4 Peruvian sites (CRONICAS Cohort Study, 2010) were used. The SES indicators considered were monthly family income (n = 3,220), educational attainment (n = 3,598), and assets index (n = 3,601). Behavioral risk factors included current tobacco use, alcohol drinking, physical activity, daily intake of fruits and vegetables, and no control of salt intake. Cardiometabolic risk factors included obesity, elevated waist circumference, hypertension, insulin resistance, diabetes mellitus, low high-density lipoprotein cholesterol, and high triglyceride levels. RESULTS: In the overall population, 41.6% reported a monthly family income

Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts.

Childhood growth is of interest in medical research concerned with determinants and consequences of variation from healthy growth and development. Linear spline multilevel modelling is a useful approach for deriving individual summary measures of growth, which overcomes several data issues (co-linearity of repeat measures, the requirement for all individuals to be measured at the same ages and bias due to missing data). Here, we outline the application of this methodology to model individual trajectories of length/height and weight, drawing on examples from five cohorts from different generations and different geographical regions with varying levels of economic development. We describe the unique features of the data within each cohort that have implications for the application of linear spline multilevel models, for example, differences in the density and inter-individual variation in measurement occasions, and multiple sources of measurement with varying measurement error. After providing example Stata syntax and a suggested workflow for the implementation of linear spline multilevel models, we conclude with a discussion of the advantages and disadvantages of the linear spline approach compared with other growth modelling methods such as fractional polynomials, more complex spline functions and other non-linear models.

Adverse childhood experiences: Prevalence and related factors in adolescents of a Brazilian birth cohort.

Adverse childhood experiences (ACEs) can affect people's health and wellbeing not only at the time the ACE is experienced, but also later in life. The majority of studies on ACEs are carried out in high-income countries and little is known about its prevalence in low and middle-income countries. Thus, the aim of this study was to assess the prevalence of ACEs, associations between ACEs and sociodemographic factors, and the interrelationship between types of ACEs in adolescents of a Brazilian birth cohort. Data from 3,951 adolescents (78.4% of the original cohort) from the 1993 Pelotas Cohort were analyzed. Seven types of ACEs were assessed in those up to 18 years old: physical abuse, sexual abuse, physical neglect, emotional neglect, domestic violence, parental separation and parental death. The most common ACE was parental separation (42%), followed by emotional neglect (19.7%) and domestic violence (10.3%). Approximately 85% of the adolescents experienced at least one ACE, and females reported a higher number of adversities. Several socioeconomic, demographic and family-related characteristics were associated with the occurrence of ACEs, e.g. non-white skin color, low family income, low maternal schooling, absence of mother's partner, maternal smoking, and poor maternal mental health. A strong interrelationship was observed among the ACEs, indicating clustering of risk. These aspects should be considered by health and social care professionals in the prevention and identification of childhood adversities.