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Higher adult child educational attainment may benefit older parents psychosocial well-being in later life. This may be particularly important in low- and middle-income countries, where recent generations have experienced comparatively large increases in educational attainment. We used data from the 2012 Mexican Health and Aging Study, a nationally representative study of adults aged ≥50 years and leveraged the exogenous variation in adult child education induced by Mexicos compulsory schooling law passed in 1993. We employed two-stage least squares (2SLS) regression to estimate the effects of increased schooling among adult children on parents (respondents) depressive symptoms and life satisfaction scores, controlling for demographic and socioeconomic characteristics. We considered heterogeneity by parent and child gender and other sociodemographic characteristics. Our study included 7186 participants with an average age of 60.1 years; 54.9% were female. In the 2SLS analyses, increased schooling among oldest adult children was associated with fewer depressive symptoms (β = -0.25; 95% CI: -0.51, 0.00) but no difference in life satisfaction (β = 0.01; 95% CI: -0.22, 0.25). Stratified models indicated differences in the magnitude of association with depressive symptoms for mothers (β = -0.27, 95% CI: -0.56, 0.01) and fathers (β = -0.18, 95% CI: -0.63, 0.26) and when considering increased schooling of oldest sons (β = -0.37; 95% CI: -0.73, -0.02) and daughters (β = -0.05, 95% CI: -0.23, 0.13). No parent and child gender differences were found for life satisfaction. Power was limited to detect heterogeneity across other sociodemographic characteristics in the second stage although first-stage estimates were larger for urban (vs. rural) dwelling and more (vs. less) highly educated respondents. Results were similar when considering the highest educated child as well as increased schooling across all children. Our findings suggest that longer schooling among current generations of adult children, particularly sons, may benefit their older parents psychosocial well-being.

Background: Multiple studies have shown that DNA methylation (DNAm) models of protein abundance can be informative about exposure, phenotype and disease risk. Here we investigate and provide descriptive details of the capacity of DNAm to capture non-genetic variation in protein abundance across the lifecourse. Methods: We evaluated the performance of 14 previously published DNAm models of protein abundance (episcores) in peripheral blood from a large adult population using the Avon Longitudinal Study of Parents and Children (ALSPAC) at ages 7–24 and their mothers antenatally and in middle age (N range = 145–1464). New age-specific episcores were trained in ALSPAC and evaluated at different ages. In all instances, episcore–protein associations were evaluated with and without adjustment for genetics. The association between longitudinal protein stability and longitudinal episcore projection was also evaluated, as was sex-specificity of episcores derived solely in female participants. Findings: Of the 14 Gadd episcores, 10 generated estimates associated with abundance in middle age, 9 at age 24, and none at age 9. Eight of these episcores explained variation beyond genotype in adulthood (6 at age 24; 7 at midlife). At age 9, the abundances of 22 proteins could be modelled by DNAm, 7 beyond genotype of which one trained model generated informative estimates at ages 24 and in middle age. At age 24, 31 proteins could be modelled by DNAm, 19 beyond genotype, of which 5 trained models generated informative estimates at age 9 and 8 in middle age. In middle age, 23 proteins could be modelled, 13 beyond genotype, of which 3 were informative at age 9 and 7 at age 24. Interpretation: We observed that episcores performed better at older ages than in children with several episcores capturing non-genetic variation at all ages. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple studies have shown that DNA methylation (DNAm) models of protein abundance can be informative about exposure, phenotype and disease risk. Here we investigate and provide descriptive details of the capacity of DNAm to capture non-genetic variation in protein abundance across the lifecourse. Methods We evaluated the performance of 14 previously published DNAm models of protein abundance (episcores) in peripheral blood from a large adult population using the Avon Longitudinal Study of Parents and Children (ALSPAC) at ages 7–24 and their mothers antenatally and in middle age (N range = 145–1464). New age-specific episcores were trained in ALSPAC and evaluated at different ages. In all instances, episcore–protein associations were evaluated with and without adjustment for genetics. The association between longitudinal protein stability and longitudinal episcore projection was also evaluated, as was sex-specificity of episcores derived solely in female participants. Findings Of the 14 Gadd episcores, 10 generated estimates associated with abundance in middle age, 9 at age 24, and none at age 9. Eight of these episcores explained variation beyond genotype in adulthood (6 at age 24; 7 at midlife). At age 9, the abundances of 22 proteins could be modelled by DNAm, 7 beyond genotype of which one trained model generated informative estimates at ages 24 and in middle age. At age 24, 31 proteins could be modelled by DNAm, 19 beyond genotype, of which 5 trained models generated informative estimates at age 9 and 8 in middle age. In middle age, 23 proteins could be modelled, 13 beyond genotype, of which 3 were informative at age 9 and 7 at age 24. Interpretation We observed that episcores performed better at older ages than in children with several episcores capturing non-genetic variation at all ages.

Background Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging. Methods and Results In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end‐diastolic volume: β=0.24 [95% CI, 0.15–0.33]; P=3×10−7) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat‐free mass and childhood height, respectively. Conclusions Our findings suggest that, although childhood body size has a long‐term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.

Context: Previous studies have shown that exposure to maternal gestational diabetes mellitus (GDM) is associated with increased offspring body mass index (BMI) and risk for overweight or obesity. Objective: This study aimed to explore differences in BMI trajectories among youth exposed or not exposed to maternal GDM and understand whether these associations differ across life stages. Methods: Data from 403 mother/child dyads (76 exposed; 327 not exposed) participating in the longitudinal Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado were used. Participants who had 2 or more longitudinal height measurements from 27 months to a maximum of 19 years were included in the analysis. Life stages were defined using puberty related timepoints: early childhood (27 months to pre-adolescent dip [PAD, average age 5.5 years]), middle childhood (from PAD to age at peak height velocity [APHV, average age 12.2 years]), and adolescence (from APHV to 19 years). Separate general linear mixed models, stratified by life stage, were used to assess associations between GDM exposure and offspring BMI. Results: There was not a significant association between exposure to GDM and BMI trajectories during early childhood (P = .27). In middle childhood, participants exposed to GDM had higher BMI trajectories compared to those not exposed (males: P = .005, females: P = .002) and adolescent (P = .02) periods. Conclusion: Our study indicates that children who are exposed to GDM may experience higher BMI trajectories during middle childhood and adolescence, but not during early childhood. These data suggest that efforts to prevent childhood obesity among those exposed in utero to maternal GDM should start before pubertal onset. [ABSTRACT FROM AUTHOR]

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.

Background Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. Methods We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child's 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure. Results Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70–0.94 and 0.88, 95% CI: 0.82–0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05–1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81–0.95 to 1.00, 95% CI: 0.91–1.10). Conclusions The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure. [ABSTRACT FROM AUTHOR]

Background: Findings from Mendelian randomization (MR) studies are conventionally interpreted as lifelong effects, which typically do not provide insight into the molecular mechanisms underlying the effect of an exposure on an outcome. In this study, we apply two recently developed MR approaches (known as ‘lifecourse’ and ‘tissue-partitioned’ MR) to investigate lifestage-specific effects and tissues of action in the relationship between adiposity and circulating leptin levels. Methods: Genetic instruments for childhood and adult adiposity were incorporated into a multivariable MR (MVMR) framework to estimate lifestage-specific effects on leptin levels measured during early life (mean age: 10 y) in the Avon Longitudinal Study of Parents and Children and in adulthood (mean age: 55 y) using summary-level data from the deCODE Health study. This was followed by partitioning body mass index (BMI) instruments into those whose effects are putatively mediated by gene expression in either subcutaneous adipose or brain tissues, followed by using MVMR to simultaneously estimate their separate effects on childhood and adult leptin levels. Results: There was strong evidence that childhood adiposity has a direct effect on leptin levels at age 10 y in the lifecourse (β = 1.10 SD change in leptin levels, 95% CI = 0.90–1.30, p=6 × 10-28), whereas evidence of an indirect effect was found on adulthood leptin along the causal pathway involving adulthood body size (β = 0.74, 95% CI = 0.62–0.86, p=1 × 10-33). Tissue-partitioned MR analyses provided evidence to suggest that BMI exerts its effect on leptin levels during both childhood and adulthood via brain tissue-mediated pathways (β = 0.79, 95% CI = 0.22–1.36, p=6 × 10-3 and β = 0.51, 95% CI = 0.32–0.69, p=1 × 10-7, respectively). Conclusions: Our findings demonstrate the use of lifecourse MR to disentangle direct and indirect effects of early-life exposures on time-varying complex outcomes. Furthermore, by integrating tissue-specific data, we highlight the etiological importance of appetite regulation in the effect of adiposity on leptin levels. Funding: This work was supported by the Integrative Epidemiology Unit, which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1).

Lifecourse Mendelian randomization is a causal inference technique which harnesses genetic variants with time-varying effects to develop insight into the influence of age-dependent lifestyle factors on disease risk. Here, we apply this approach to evaluate whether childhood body size has a direct consequence on 8 major disease endpoints by analysing parental history data from the UK Biobank study. Our findings suggest that, whilst childhood body size increases later risk of outcomes such as heart disease (odds ratio (OR) = 1.15, 95% CI = 1.07 to 1.23, P = 7.8 × 10− 5) and diabetes (OR = 1.43, 95% CI = 1.31 to 1.56, P = 9.4 × 10− 15) based on parental history data, these findings are likely attributed to a sustained influence of being overweight for many years over the lifecourse. Likewise, we found evidence that remaining overweight throughout the lifecourse increases risk of lung cancer, which was partially mediated by lifetime smoking index. In contrast, using parental history data provided evidence that being overweight in childhood may have a protective effect on risk of breast cancer (OR = 0.87, 95% CI = 0.78 to 0.97, P = 0.01), corroborating findings from observational studies and large-scale genetic consortia. Large-scale family disease history data can provide a complementary source of evidence for epidemiological studies to exploit, particularly given that they are likely more robust to sources of selection bias (e.g. survival bias) compared to conventional case control studies. Leveraging these data using approaches such as lifecourse Mendelian randomization can help elucidate additional layers of evidence to dissect age-dependent effects on disease risk. [ABSTRACT FROM AUTHOR]

There is increasing interest in modelling longitudinal dietary data and classifying individuals into subgroups (latent classes) who follow similar trajectories over time. These trajectories could identify population groups and time points amenable to dietary interventions. This paper aimed to provide a comparison and overview of two latent class methods: group-based trajectory modelling (GBTM) and growth mixture modelling (GMM). Data from 2963 mother–child dyads from the longitudinal Southampton Women's Survey were analysed. Continuous diet quality indices (DQI) were derived using principal component analysis from interviewer-administered FFQ collected in mothers pre-pregnancy, at 11- and 34-week gestation, and in offspring at 6 and 12 months and 3, 6–7 and 8–9 years. A forward modelling approach from 1 to 6 classes was used to identify the optimal number of DQI latent classes. Models were assessed using the Akaike and Bayesian information criteria, probability of class assignment, ratio of the odds of correct classification, group membership and entropy. Both methods suggested that five classes were optimal, with a strong correlation (Spearman's = 0·98) between class assignment for the two methods. The dietary trajectories were categorised as stable with horizontal lines and were defined as poor (GMM = 4 % and GBTM = 5 %), poor-medium (23 %, 23 %), medium (39 %, 39 %), medium-better (27 %, 28 %) and best (7 %, 6 %). Both GBTM and GMM are suitable for identifying dietary trajectories. GBTM is recommended as it is computationally less intensive, but results could be confirmed using GMM. The stability of the diet quality trajectories from pre-pregnancy underlines the importance of promotion of dietary improvements from preconception onwards. [ABSTRACT FROM AUTHOR]

Spatial lifecourse epidemiology is an interdisciplinary field that utilizes advanced spatial, location-based, and artificial intelligence technologies to investigate the long-term effects of environmental, behavioural, psychosocial, and biological factors on health-related states and events and the underlying mechanisms. With the growing number of studies reporting findings from this field and the critical need for public health and policy decisions to be based on the strongest science possible, transparency and clarity in reporting in spatial lifecourse epidemiologic studies is essential. A task force supported by the International Initiative on Spatial Lifecourse Epidemiology (ISLE) identified a need for guidance in this area and developed a Spatial Lifecourse Epidemiology Reporting Standards (ISLE-ReSt) Statement. The aim is to provide a checklist of recommendations to improve and make more consistent reporting of spatial lifecourse epidemiologic studies. The STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement for cohort studies was identified as an appropriate starting point to provide initial items to consider for inclusion. Reporting standards for spatial data and methods were then integrated to form a single comprehensive checklist of reporting recommendations. The strength of our approach has been our international and multidisciplinary team of content experts and contributors who represent a wide range of relevant scientific conventions, and our adherence to international norms for the development of reporting guidelines. As spatial, location-based, and artificial intelligence technologies used in spatial lifecourse epidemiology continue to evolve at a rapid pace, it will be necessary to revisit and adapt the ISLE-ReSt at least every 2-3 years from its release.

Background: We previously showed that exposure to 5-methylchrysene (5MC) and other methylated polycyclic aromatic hydrocarbons (PAHs) best explains lung cancer risks in a case-control study among non-smoking women using smoky coal in China. Time-related factors (e.g., age at exposure) and non-linear relations were not explored. Objective: We investigated the relation between coal-derived air pollutants and lung cancer mortality using data from a large retrospective cohort. Methods: Participants were smoky (bituminous) or smokeless (anthracite) coal users from a cohort of 42,420 subjects from four communes in XuanWei. Follow-up was from 1976 to 2011, during which 4,827 deaths from lung-cancer occurred. Exposures were predicted for 43 different pollutants. Exposure clusters were identified using hierarchical clustering. Cox regression was used to estimate exposure–response relations for 5MC, while effect modification by age at exposure was investigated for cluster prototypes. A Bayesian penalized multi-pollutant model was fitted on a nested case-control sample, with more restricted models fitted to investigate non-linear exposure–response relations. Results: We confirmed the strong exposure–response relation for 5MC (Hazard Ratio [95% Confidence Interval] = 2.5 [2.4, 2.6] per standard-deviation (SD)). We identified four pollutant clusters, with all but two PAHs in a single cluster. Exposure to PAHs in the large cluster was associated with a higher lung cancer mortality rate (HR [95%CI] = 2.4 [2.2, 2.6] per SD), while exposure accrued before 18 years of age appeared more important than adulthood exposures. Results from the multi-pollutant model identified anthanthrene (ANT) and benzo(a)chrysene (BaC) as risk factors. 5MC remained strongly associated with lung cancer in models that included ANT and BaC and also benzo(a)pyrene (BaP). Conclusion: We confirmed the link between PAH exposures and lung cancer in smoky coal users and found exposures before age 18 to be especially important. We found some evidence for the carcinogen 5MC and non-carcinogens ANT and BaC.

BackgroundIn middle age, stroke incidence is higher among black than white Americans. For unknown reasons, this inequality decreases and reverses with age. We conducted simulations to evaluate whether selective survival could account for observed age patterning of black-white stroke inequalities.MethodsWe simulated birth cohorts of 20,000 blacks and 20,000 whites with survival distributions based on US life tables for the 1919-1921 birth cohort. We generated stroke incidence rates for ages 45-94 years using Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study rates for whites and setting the effect of black race on stroke to incidence rate difference (IRD) = 20/10,000 person-years at all ages, the inequality observed at younger ages in REGARDS. We compared observed age-specific stroke incidence across scenarios, varying effects of U, representing unobserved factors influencing mortality and stroke risk.ResultsDespite a constant adverse effect of black race on stroke risk, the observed black-white inequality in stroke incidence attenuated at older age. When the hazard ratio for U on stroke was 1.5 for both blacks and whites, but U only directly influenced mortality for blacks (hazard ratio for U on mortality =1.5 for blacks; 1.0 for whites), stroke incidence rates in late life were lower among blacks (average observed IRD = -43/10,000 person-years at ages 85-94 years versus causal IRD = 20/10,000 person-years) and mirrored patterns observed in REGARDS.ConclusionsA relatively moderate unmeasured common cause of stroke and survival could fully account for observed age attenuation of racial inequalities in stroke.

There is growing evidence that adult child educational attainment is associated with older parents' physical health and longevity. Scholars have hypothesized that these associations may be driven by health-behavior pathways, whereby adult children with more education may share information about healthy lifestyles, role-model healthier behaviors, and/or have more economic resources to support leisure-based physical activity or the purchase of healthy foods for older parents. However, this relationship has not been comprehensively evaluated with methods capable of addressing the confounding bias expected for observational studies on this topic. We estimated the association between increased adult child schooling and older parents' health behaviors using data from the Survey for Health, Aging and Retirement in Europe (SHARE) (n = 8195). We leveraged changes to compulsory schooling laws that would have impacted respondents' adult children as quasi-experiments and estimated the association between increased schooling among oldest adult children and respondents' (parents') body mass index, obesity, physical inactivity, excessive drinking, and current smoking using two-stage least squares regression. Each year of increased schooling among oldest adult children was associated with a lower risk of current smoking (β: −0.029, 95% CI: −0.056, −0.003), physical inactivity (β: −0.034, 95% confidence interval [CI]: −0.077, 0.009), obesity (β: −0.038, 95% CI: −0.065, −0.011) and lower body mass index (β: −0.37, 95% CI: −0.73, −0.02). The direction of associations with excessive drinking varied by parent gender (β: −0.027, 95% CI: −0.046, −0.007 for mothers; β: 0.068, 95% CI: −0.011, 0.148 for fathers). Increases in adult child schooling may have upward influences on parents' late-life health behaviors, although there may be some differences by parent gender. Findings should be replicated across other global settings and studies should directly evaluate parent health behaviors as mediators of the relationship between increased adult child schooling and older parents’ longevity.

Background: Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation. Methods: In this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse. Results: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range = 8.9–11.5 years) after accounting for the effect of the adult body size genetic score (beta = −0.32, 95% CI = −0.54 to –0.10, p=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range = 40–69 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = −0.17, 95% CI = −0.21 to –0.13, p=4.6 × 10-17). Conclusions: Our findings have important implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies. Funding: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1).

Distribution of environmental hazards and vulnerability to their effects vary across socioeconomic groups. Our objective was to analyse the relationship between child socioeconomic position (SEP) at birth and the external exposome at pre-school age (0–4 years). This study included more than 60,000 children from eight cohorts in eleven European cities (Oslo, Copenhagen, Bristol, Bradford, Rotterdam, Nancy, Poitiers, Gipuzkoa, Sabadell, Valencia and Turin). SEP was measured through maternal education and a standardised indicator of household income. Three child exposome domains were investigated: behavioral, diet and urban environment. We fitted separate logistic regression model for each exposome variable - dichotomised using the city-specific median - on SEP (medium/low vs high) adjusting for maternal age, country of birth and parity. Analyses were carried out separately in each study-area. Low-SEP children had, consistently across study-areas, lower Odds Ratios (ORs) of breastfeeding, consumption of eggs, fish, fruit, vegetables and higher ORs of TV screen time, pet ownership, exposure to second-hand smoke, consumption of dairy, potatoes, sweet beverages, savory biscuits and crisps, fats and carbohydrates. For example, maternal education-breastfeeding OR (95% Confidence Interval (CI)) ranged from 0.18 (0.14–0.24) in Bristol to 0.73 (0.58–0.90) in Oslo. SEP was also strongly associated with the urban environment with marked between-city heterogeneity. For example, income-PM 2.5 OR (95%CI) ranged from 0.69 (0.47–1.02) in Sabadell to 2.44 (2.16–2.72) in Oslo. Already at pre-school age, children with lower SEP have consistently poorer diets and behaviours, which might influence their future health and wellbeing. SEP-urban environment relationships are strongly context-dependent. • Harmonised data on 61378 children from eight cohorts in eleven European cities. • Two indicators of socioeconomic position (SEP): household income and maternal education. • Low SEP children had consistently poor diet and unhealthy behaviours at preschool age. • SEP-urban environment relationships are strongly context-dependent. • The preschool age period is a window of opportunity to mitigate SEP inequalities. [ABSTRACT FROM AUTHOR]

Objective: Obesity and cardiovascular disease are major global public health problems. Maternal obesity has been linked to multiple adverse health consequences for both mother and baby. Obesity during pregnancy may adversely alter the intrauterine environment, which has been hypothesised to predispose the offspring to poorer cardiovascular health throughout life. In this paper, we systematically review current literature examining the links between maternal obesity and offspring cardiovascular health. Methods: This study is registered with PROSPERO (CRD42021278567) and was conducted in accordance with the PRISMA guidelines. A comprehensive systematic literature search was conducted, including two electronic databases (Ovid Medline, Embase), cross-referencing, author searching, and grey literature searches. We selected studies exploring the relationship between maternal obesity and offspring cardiovascular health, using pre-defined eligibility criteria. Studies were critically appraised using the ROBINS-I tool. Results: From 1,214 results, 27 articles met the eligibility criteria. Multiple cardiovascular outcomes were considered, including congenital heart disease, cardiometabolic parameters, and cardiovascular diseases in neonates, children, and adults. In these studies, maternal obesity was consistently associated with congenital heart disease, several adverse cardiometabolic parameters throughout life including higher body mass index and insulin levels, and greater risk of cardiovascular disease in adulthood. Hypothesized underlying mechanisms are complex and multifactorial comprising genetic, environmental, and socioeconomic components, which can be difficult to quantify. Heterogeneity in study designs, highly selected study samples, and high risk of bias in some studies limit conclusions regarding causality. Conclusions: We identified consistent evidence of links between maternal obesity and poorer offspring cardiovascular health throughout the lifecourse, extending from the neonatal period into adulthood. Although underlying mechanisms are unclear, our findings support consideration of targeted maternal obesity prevention for promotion of offspring cardiovascular health. This all-encompassing systematic review provides critical appraisal of the latest evidence, defines gaps and biases of existing literature, and may inform potential new public health strategies for cardiovascular disease prevention. Systematic Review Registration: [ https://www.crd.york.ac.uk/prospero ], identifier PROSPERO (CRD42021278567). [ABSTRACT FROM AUTHOR]

Abstract Background In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives’ practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments. Methods Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments. Results Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1–7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking. Conclusions Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives’ implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community.

Objective: Early menarche is associated with uterine fibroid risk, but the association between menarcheal timing and fibroid severity remains to be explored. Given the hormonal dependence of fibroids, earlier menarche may increase physical burden (e.g., number of fibroids) and/or symptoms (e.g., heavy menstrual bleeding), though the two are not always correlated. We hypothesized that individuals with earlier menarche are more likely to have severe fibroids. Design: We analyzed observational data using linear regression models to examine the association between earlier age at menarche and fibroid severity. Subjects : Individuals seeking hysterectomy (n = 110) for fibroid management at a hospital in Washington, D.C. from 2014 to 2021 as part of the Fibroids, Observational Research on Genes and the Environment study. Exposure: Participants recalled age at menarche during adulthood. We modeled age at menarche continuously, and we defined early menarche as menarche before 12 years in descriptive analyses. Main Outcome Measures: We evaluated three types of fibroid severity outcomes: self-reported symptoms using validated scales, clinical parameters (e.g., fibroid number and size), and age at hysterectomy. Results: In our predominantly Black sample, early menarche (i.e., <12 years) was reported by 25.5% (28/110) of participants. In adjusted linear models, earlier menarche was associated with increased symptom severity [ b = -3.3 (95% CI: -6.05, -0.56)], younger age at hysterectomy [ b = 0.8 (95% CI: 0.2, 1.41)], and uterine weight over 250 g (compared with ≤250 g) [ b = -0.05 (95% CI: -0.11, -0.00)], but not with other measures of physical fibroid burden. Conclusion: Earlier menarche was associated with measures of fibroid severity. Prolonged exposure to estrogen via early menarche may accelerate the tumorigenesis process. Patient-reported symptoms as well as measures of physical burden should be considered when investigating the etiology of fibroid-related morbidity.

Study Question: Is cesarean delivery associated with earlier offspring pubertal development?Summary Answer: We identified that boys born by cesarean delivery developed puberty earlier, evidenced by an earlier age at peak height velocity and earlier attainment of puberty score > 1, than boys born by vaginal delivery.What Is Known Already: Cesarean delivery is posited to have long-term effects on health outcomes. However, few studies have examined whether mode of delivery is related to pubertal development.Study Design, Size, Duration: Prospective pre-birth cohort study consisting of 1485 mother-child pairs enrolled during pregnancy from obstetric practices and followed up until early adolescence (median age 12.9 years). Participant inclusion required data on mode of delivery and at least one measure of pubertal development.Participants/materials, Setting, Methods: Participants are children from the Project Viva study. We abstracted information on delivery mode from electronic medical records from children followed since birth (1999-2002) and examined the following markers of pubertal development: age at peak height velocity (APHV); age at menarche (girls only); parent-reported pubertal development score; and child-reported pictograph Tanner pubic hair staging. We used multivariable regression models to examine associations of delivery mode with these four pubertal indices, adjusting for the following confounders: demographic and socioeconomic factors; maternal height, pre-pregnancy BMI, total gestational weight gain, pregnancy conditions, parity, and maternal age at menarche; paternal height and BMI; gestational age at delivery and birthweight-for-gestational-age z-score.Main Results and the Role Of Chance: In this study, 23.2% of children were born by cesarean delivery. Girls had an earlier APHV, had a higher pubertal score throughout childhood and in early adolescence, and were more likely to attain puberty score >1 and Tanner pubic hair Stage >1 earlier compared to boys. Mean (SD) age at menarche in girls was 12.4 (1.0) years. Boys born by cesarean delivery had significantly earlier APHV (β -0.23 years; 95% CI -0.40, -0.05) and higher risk of earlier attainment of puberty score > 1 (hazard ratio 1.09; 95% CI 1.01, 1.19) than boys born by vaginal delivery, after adjusting for confounders. These associations were not mediated by pre-pubertal BMI and were similar for planned (no labor) and unplanned (labor) cesarean delivery. No associations were observed between delivery mode and time to attain Tanner pubic hair Stage > 1 in boys. In girls, mode of delivery was not associated with any of the measured pubertal development markers.Limitations, Reasons For Caution: This study used, as secondary outcomes, parent- and child-reported measures of pubertal development, which may be more prone to error and misclassification than information collected by trained observers or physicians during clinical examinations. The findings may also not be generalizable to populations from different settings, because all participants lived in one geographic area, were well educated, and had health care.Wider Implications Of the Findings: Our findings provide support for cesarean delivery as a potential indicator of identifying children who are likely to experience earlier pubertal development; however, more studies are needed to confirm or refute these observations.Study Funding/competing Interest(s): The project was funded by grants from the National Institutes of Health. The authors have no financial relationships or competing interests to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community. [ABSTRACT FROM AUTHOR]

Background: In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives' practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments.Methods: Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments.Results: Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1-7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking.Conclusions: Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives' implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community. [ABSTRACT FROM AUTHOR]

This paper examines the association between financial hardship in childhood and adulthood, and depression and anxiety in adulthood with reference to the accumulation, critical period and social mobility hypotheses in lifecourse epidemiology. Using the BBC Stress test, linear regression models were used to investigate the associations for the whole population and stratifying by gender and adjusting for age and highest education attainment. The critical period hypothesis was not confirmed. The accumulation hypothesis was confirmed and stratifying by gender women had a higher estimated mean GAD score if they were poor in both childhood and adulthood compared to men. Our findings do not support the social mobility hypothesis. However, stratifying by gender, a clear difference emerged with upward mobility having a favourable impact (lower) on women's mean GAD scores, while upward social mobility in adulthood did not attenuate the impact of financial hardship in childhood or men. The impact of financial hardship in childhood on later mental health outcomes is particularly concerning for future health outcomes as current levels of child poverty increases in the UK.

This paper examines the association between financial hardship in childhood and adulthood, and depression and anxiety in adulthood with reference to the accumulation, critical period and social mobility hypotheses in lifecourse epidemiology. Using the BBC Stress test, linear regression models were used to investigate the associations for the whole population and stratifying by sex and adjusting for age and highest education attainment. The critical period hypothesis was not confirmed. The accumulation hypothesis was confirmed and stratifying by sex women had a higher estimated mean GAD score if they were poor in both childhood and adulthood compared to men. Our findings do not support the social mobility hypothesis. However, stratifying by sex, a clear difference emerged with upward mobility having a favourable impact (lower) on women's mean GAD scores, while upward social mobility in adulthood did not attenuate the impact of financial hardship in childhood or men. The impact of financial hardship in childhood on later mental health outcomes is particularly concerning for future health outcomes as current levels of child poverty increases in the UK.

Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes. Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders. Subjects and methods: Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC. Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC. Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.

Aims/hypothesis: The aim of this work was to investigate the association of maternal HbA1c during mid-pregnancy with biomarkers of glucose–insulin homeostasis during early childhood (4–7 years of age) and to assess whether and how offspring adiposity at birth and at age 4–7 years mediates this relationship among 345 mother–child pairs in the Healthy Start Study. Methods: The exposure was maternal HbA1c (mmol/mol) measured at 20–34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4–7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4–7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. Results: There was a significant total effect of maternal HbA1c on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA1c and offspring glucose (p trend <0.001), and an inverse trend across tertiles of HbA1c and offspring 1/insulin (p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA1c, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI −0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4–7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. Conclusions/interpretation: Offspring of women with higher HbA1c during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity. [ABSTRACT FROM AUTHOR]

Background: Controlling for maturational status and timing is crucial in lifecourse epidemiology. One popular non-invasive measure of maturity is the age at peak height velocity (PHV). There are several ways to estimate age at PHV, but it is unclear which of these to use in practice. Aim: To find the optimal approach for estimating age at PHV. Subjects and methods: Methods included the Preece & Baines non-linear growth model, multi-level models with fractional polynomials, SuperImposition by Translation And Rotation (SITAR) and functional data analysis. These were compared through a simulation study and using data from a large cohort of adolescent boys from the Christ’s Hospital School. Results: The SITAR model gave close to unbiased estimates of age at PHV, but convergence issues arose when measurement error was large. Preece & Baines achieved close to unbiased estimates, but shares similarity with the data generation model for our simulation study and was also computationally inefficient, taking 24 hours to fit the data from Christ’s Hospital School. Functional data analysis consistently converged, but had higher mean bias than SITAR. Almost all methods demonstrated strong correlations (r > 0.9) between true and estimated age at PHV. Conclusions: Both SITAR or the PBGM are useful models for adolescent growth and provide unbiased estimates of age at peak height velocity. Care should be taken as substantial bias and variance can occur with large measurement error.

Background: Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging., Methods and Results: In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end-diastolic volume: β=0.24 [95% CI, 0.15-0.33]; P =3×10 -7 ) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat-free mass and childhood height, respectively., Conclusions: Our findings suggest that, although childhood body size has a long-term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.

Higher adult child educational attainment may benefit older parents' psychosocial well-being in later life. This may be particularly important in low- and middle-income countries, where recent generations have experienced comparatively large increases in educational attainment. We used data from the 2012 Mexican Health and Aging Study, a nationally representative study of adults aged ≥50 years and leveraged the exogenous variation in adult child education induced by Mexico's compulsory schooling law passed in 1993. We employed two-stage least squares (2SLS) regression to estimate the effects of increased schooling among adult children on parents' (respondents') depressive symptoms and life satisfaction scores, controlling for demographic and socioeconomic characteristics. We considered heterogeneity by parent and child gender and other sociodemographic characteristics. Our study included 7186 participants with an average age of 60.1 years; 54.9% were female. In the 2SLS analyses, increased schooling among oldest adult children was associated with fewer depressive symptoms (β = -0.25; 95% CI: -0.51, 0.00) but no difference in life satisfaction (β = 0.01; 95% CI: -0.22, 0.25). Stratified models indicated differences in the magnitude of association with depressive symptoms for mothers (β = -0.27, 95% CI: -0.56, 0.01) and fathers (β = -0.18, 95% CI: -0.63, 0.26) and when considering increased schooling of oldest sons (β = -0.37; 95% CI: -0.73, -0.02) and daughters (β = -0.05, 95% CI: -0.23, 0.13). No parent and child gender differences were found for life satisfaction. Power was limited to detect heterogeneity across other sociodemographic characteristics in the second stage although first-stage estimates were larger for urban (vs. rural) dwelling and more (vs. less) highly educated respondents. Results were similar when considering the highest educated child as well as increased schooling across all children. Our findings suggest that longer schooling among current generations of adult children, particularly sons, may benefit their older parents' psychosocial well-being., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024 The Authors.)

'Unexplained residuals' models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework. Importantly, we explicitly place unexplained residual models in a causal framework using directed acyclic graphs. This allows for theoretical justification of appropriate confounder adjustment and provides a framework for extending our results to more complex scenarios than those examined in this paper. We also discuss several interpretational issues relating to unexplained residual models within a causal framework. We argue that unexplained residual models offer no additional insights compared to traditional regression methods, and, in fact, are more challenging to implement; moreover, they artificially reduce estimated standard errors. Consequently, we conclude that unexplained residual models, if used, must be implemented with great care. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations of in utero exposure to maternal diabetes with surrogate measures of offspring pubertal timing (age at peak height velocity [APHV]) and speed of pubertal growth (peak height velocity [PHV]).Study Design: Data from 77 exposed and 340 unexposed youth followed from age 2 to 19 years (51% non-Hispanic white, 50% female) were analyzed using the Exploring Perinatal Outcomes among Children study, a historical prospective cohort. Maternal diabetes status was collected from obstetric records, and child heights from 2 years to current age from pediatric records. Other covariates were collected during research visits. The superimposition by translation and rotation method, using height measurements (4-52 per participant), modeled APHV and PHV. Accelerated failure time analyses were used to test whether exposure to maternal diabetes was associated with younger APHV and faster PHV.Results: Adjusting for child's sex, race/ethnicity, and socioeconomic status, median APHV was reached ~3 months earlier in youth exposed to maternal diabetes compared with unexposed youth (P < .03). Youth exposed to maternal diabetes had a faster PHV than unexposed youth: exposed girls had 10.5% greater median PHV compared with unexposed girls and exposed boys had a 4.0% greater median PHV compared with unexposed boys (P < .001 for exposure by sex interaction).Conclusions: Our findings provide evidence that exposure to maternal diabetes in utero is associated with earlier pubertal timing and faster pubertal growth. Whether earlier puberty or faster speed of pubertal growth mediates the association between maternal diabetes exposure and later chronic disease risk remains to be studied. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the independent and combined relationships of body mass index (BMI) peak and rebound with adiposity, insulin resistance and metabolic risk later in life. We used data from Project Viva, a well-characterized birth cohort from Boston with repeated measures of BMI, to help fill this gap.Methods: Among 1681 children with BMI data from birth to mid childhood, we fitted individual BMI trajectories using mixed-effects models with natural cubic splines and estimated age, and magnitude of BMI, at peak (in infancy) and rebound (in early childhood). We obtained cardiometabolic measures of the children in early adolescence (median 12.9 years) and analysed their associations with the BMI parameters.Results: After adjusting for potential confounders, age and magnitude at infancy BMI peak were associated with greater adolescent adiposity, and earlier adiposity rebound was strongly associated with greater adiposity, insulin resistance and metabolic risk score independently of BMI peak. Children with a normal timing of BMI peak plus early rebound had an adverse cardiometabolic profile, characterized by higher fat mass index {β 2.2 kg/m2 [95% confidence interval (CI) 1.6, 2.9]}, trunk fat mass index [1.1 kg/m2 (0.8, 1.5)], insulin resistance [0.2 units (0.04, 0.4)] and metabolic risk score [0.4 units (0.2, 0.5)] compared with children with a normal BMI peak and a normal rebound pattern. Children without a BMI peak (no decline in BMI after the rise in infancy) also had adverse adolescent metabolic profiles.Conclusions: Early age at BMI rebound is a strong risk factor for cardiometabolic risk, independent of BMI peak. Children with a normal peak-early rebound pattern, or without any BMI decline following infancy, are at greatest risk of adverse cardiometabolic profile in adolescence. Routine monitoring of BMI may help to identify children who are at greatest risk of developing an adverse cardiometabolic profile in later life and who may be targeted for preventive interventions. [ABSTRACT FROM AUTHOR]

Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes. Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders. Subjects and methods: Data were collected from 753 offspring in the Southampton Women's Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks' gestation) and femur length (19 and 34 weeks' gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC. Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC. Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology. [ABSTRACT FROM AUTHOR]

3D-body scanning anthropometry is a suitable method for characterization of physiological development of children and adolescents, and for understanding onset and progression of disorders like overweight and obesity. Here we present a novel body typing approach to describe and to interpret longitudinal 3D-body scanning data of more than 800 children and adolescents measured in up to four follow-ups in intervals of 1 year, referring to an age range between 6 and 18 years. We analyzed transitions between body types assigned to lower-, normal- and overweight participants upon development of children and adolescents. We found a virtually parallel development of the body types with only a few transitions between them. Body types of children and adolescents tend to conserve their weight category. 3D body scanning anthropometry in combination with body typing constitutes a novel option to investigate onset and progression of obesity in children. [ABSTRACT FROM AUTHOR]

Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9–23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and self-reported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (±2y) or 45 (±2y) and body silhouettes in women and men were between 0.62–0.66 and correlations for self-reported BMI were between 0.58–0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (±2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men. [ABSTRACT FROM AUTHOR]

Background:Controlling for maturational status and timing is crucial in lifecourse epidemiology. One popular non-invasive measure of maturity is the age at peak height velocity (PHV). There are several ways to estimate age at PHV, but it is unclear which of these to use in practice. Aim:To find the optimal approach for estimating age at PHV. Subjects and methods:Methods included the Preece & Baines non-linear growth model, multi-level models with fractional polynomials, SuperImposition by Translation And Rotation (SITAR) and functional data analysis. These were compared through a simulation study and using data from a large cohort of adolescent boys from the Christ’s Hospital School. Results:The SITAR model gave close to unbiased estimates of age at PHV, but convergence issues arose when measurement error was large. Preece & Baines achieved close to unbiased estimates, but shares similarity with the data generation model for our simulation study and was also computationally inefficient, taking 24 hours to fit the data from Christ’s Hospital School. Functional data analysis consistently converged, but had higher mean bias than SITAR. Almost all methods demonstrated strong correlations (r > 0.9) between true and estimated age at PHV. Conclusions:Both SITAR or the PBGM are useful models for adolescent growth and provide unbiased estimates of age at peak height velocity. Care should be taken as substantial bias and variance can occur with large measurement error. [ABSTRACT FROM AUTHOR]

There is a growing debate with regards to the appropriate methods of analysis of growth trajectories and their association with prospective dependent outcomes. Using the example of childhood growth and adult BP, we conducted an extensive simulation study to explore four two-stage and two joint modelling methods, and compared their bias and coverage in estimation of the (unconditional) association between birth length and later BP, and the association between growth rate and later BP (conditional on birth length). We show that the two-stage method of using multilevel models to estimate growth parameters and relating these to outcome gives unbiased estimates of the conditional associations between growth and outcome. Using simulations, we demonstrate that the simple methods resulted in bias in the presence of measurement error, as did the two-stage multilevel method when looking at the total (unconditional) association of birth length with outcome. The two joint modelling methods gave unbiased results, but using the re-inflated residuals led to undercoverage of the confidence intervals. We conclude that either joint modelling or the simpler two-stage multilevel approach can be used to estimate conditional associations between growth and later outcomes, but that only joint modelling is unbiased with nominal coverage for unconditional associations. [ABSTRACT FROM AUTHOR]

Background: Findings from Mendelian randomization (MR) studies are conventionally interpreted as lifelong effects, which typically do not provide insight into the molecular mechanisms underlying the effect of an exposure on an outcome. In this study, we apply two recently developed MR approaches (known as 'lifecourse' and 'tissue-partitioned' MR) to investigate lifestage-specific effects and tissues of action in the relationship between adiposity and circulating leptin levels., Methods: Genetic instruments for childhood and adult adiposity were incorporated into a multivariable MR (MVMR) framework to estimate lifestage-specific effects on leptin levels measured during early life (mean age: 10 y) in the Avon Longitudinal Study of Parents and Children and in adulthood (mean age: 55 y) using summary-level data from the deCODE Health study. This was followed by partitioning body mass index (BMI) instruments into those whose effects are putatively mediated by gene expression in either subcutaneous adipose or brain tissues, followed by using MVMR to simultaneously estimate their separate effects on childhood and adult leptin levels., Results: There was strong evidence that childhood adiposity has a direct effect on leptin levels at age 10 y in the lifecourse (β = 1.10 SD change in leptin levels, 95% CI = 0.90-1.30, p=6 × 10 -28 ), whereas evidence of an indirect effect was found on adulthood leptin along the causal pathway involving adulthood body size (β = 0.74, 95% CI = 0.62-0.86, p=1 × 10 -33 ). Tissue-partitioned MR analyses provided evidence to suggest that BMI exerts its effect on leptin levels during both childhood and adulthood via brain tissue-mediated pathways (β = 0.79, 95% CI = 0.22-1.36, p=6 × 10 -3 and β = 0.51, 95% CI = 0.32-0.69, p=1 × 10 -7 , respectively)., Conclusions: Our findings demonstrate the use of lifecourse MR to disentangle direct and indirect effects of early-life exposures on time-varying complex outcomes. Furthermore, by integrating tissue-specific data, we highlight the etiological importance of appetite regulation in the effect of adiposity on leptin levels., Funding: This work was supported by the Integrative Epidemiology Unit, which receives funding from the UK Medical Research Council and the University of Bristol (MC&#95;UU&#95;00011/1)., Competing Interests: TR TGR is an employee of GlaxoSmithKline outside of this work, GL, GD No competing interests declared, (© 2023, Richardson et al.)

Background: Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings., Methods: We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child's 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure., Results: Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70-0.94 and 0.88, 95% CI: 0.82-0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05-1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81-0.95 to 1.00, 95% CI: 0.91-1.10)., Conclusions: The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Exposure early in life can influence adult disease and immunity, but the role of early life exposures in risk of SLE is not established.Methods: Women in a national cohort (ages 35-74) provided data on perinatal, maternal and sociodemographic factors, longest residence to age 14 and residential farm history of at least 12 months to age 18. Cases (N=124) reported SLE diagnosed age 16 years or older with use of disease modifying anti-rheumatic drugs. Non-cases (N=50,465) did not report lupus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression adjusting for age and race/ethnicity. Results: SLE was associated with low birthweight (data on 84 cases and 36,477 non-cases; 4 weeks early vs. full-term; OR=3.4; 95%CI 1.6, 7.4). Considering longest childhood residence to age 14, SLE was associated with more frequent pesticide use (e.g., at least monthly OR=2.3; 95%CI 1.3, 4.1). SLE was associated with having an early and extended childhood farm residence (i.e., prenatal/maternal farm exposure and longest childhood farm residence; OR=1.8; 95%CI 1.1, 3.0 versus neither). In those with a childhood-only farm residence of 12+ months, agricultural pesticide use was associated with SLE, with the strongest associations for direct personal exposures. Conclusions: The association of SLE with premature birth is consistent with studies in other populations, and with an observed association with low birthweight. The associations of SLE with childhood exposure to residential and agricultural pesticides warrant further study.INTRODUCTIONSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune reactivity to multiple nuclear components and inflammation, resulting in diverse clinical features and multiple organ involvement. The causes of SLE are generally not known. Racial disparities and increased familial risk suggest a genetic predisposition. It is believed that environmental factors may contribute to the development of disease, but knowledge on specific risk factors is mostly limited to occupational exposures[1]. The developmental origins hypothesis has been proposed for many adult-onset, chronic inflammatory diseases, including systemic lupus erythematosus (SLE) [2-6]. Exposures during and after gestation, including nutritional, infectious, chemical