Health care utilization and the associated costs attributable to cardiovascular disease in Ireland: a cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and disability globally. We examined healthcare service utilization and costs attributable to CVD in Ireland in the period before the introduction of a major healthcare reform in 2016. METHODS: Secondary analysis of data from 8 113 participants of the first wave of The Irish Longitudinal Study on Ageing. CVD was defined as having a self-reported doctor's diagnosis of myocardial infarction, angina, heart failure, stroke, atrial fibrillation or transient ischaemic attack. Participants self-reported the utilization of healthcare services in the year preceding the interview. Negative binomial regression with average marginal effects (AME) was used to estimate the incremental number of general practitioner (GP) and outpatient department (OPD) visits, accident and emergency department attendances and hospitalisations in population with CVD relative to population without CVD. We calculated the corresponding costs at individual and population levels, by gender and age groups. RESULTS: The prevalence of CVD was 18.2% (95% CI: 17.3, 19.0) Participants with CVD reported higher utilization of all healthcare services. In adjusted models, having CVD was associated with incremental 1.19 (95% CI: 0.99, 1.39) GP and 0.79 (95% CI: 0.65, 0.93) OPD visits. There were twice as many incremental hospitalisations in males with CVD compared to females with CVD (AME (95% CI): 0.20 (0.16, 0.23) vs 0.10 (0.07, 0.14)). The incremental cost of healthcare service use in population with CVD was an estimated €352.2 million (95% CI: €272.8, €431.7), 93% of which was due to use of secondary care services. CONCLUSION: We identified substantially increased use of healthcare services attributable to CVD in Ireland. Continued efforts aimed at CVD primary prevention and management are required.

Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry.

Plasticity and homeostatic mechanisms allow neural networks to maintain proper function while responding to physiological challenges. Despite previous work investigating morphological and synaptic effects of brain-derived neurotrophic factor (BDNF), the most prevalent growth factor in the central nervous system, how exposure to BDNF manifests at the network level remains unknown. Here we report that BDNF treatment affects rodent hippocampal network dynamics during development and recovery from glutamate-induced excitotoxicity in culture. Importantly, these effects are not obvious when traditional activity metrics are used, so we delve more deeply into network organization, functional analyses, and in silico simulations. We demonstrate that BDNF partially restores homeostasis by promoting recovery of weak and medium connections after injury. Imaging and computational analyses suggest these effects are caused by changes to inhibitory neurons and connections. From our in silico simulations, we find that BDNF remodels the network by indirectly strengthening weak excitatory synapses after injury. Ultimately, our findings may explain the difficulties encountered in preclinical and clinical trials with BDNF and also offer information for future trials to consider.

Childhood socioeconomic position and sex-specific trajectories of metabolic traits across early life: prospective cohort study.

BACKGROUND: Socioeconomic inequalities in cardiovascular disease risk begin early in life and are more pronounced in females than males later in life. Causal atherogenic traits explaining this are not well understood. We explored sex-specific associations between childhood socioeconomic position (SEP) and molecular measures of systemic metabolism across early life. METHODS: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort in southwest England. Pregnant women with an expected delivery date between 1991 and 1992 were invited to participate. Maternal education was the primary indicator of SEP. Concentrations of 148 metabolic traits from targeted metabolomics (nuclear magnetic resonance spectroscopy) from research clinics at ages 7, 15, 18 and 25 years were analysed. The sex-specific slope index of inequality (SII) in trajectories of metabolic traits was estimated using multilevel models. FINDINGS: Total number of participants included was 6537 (12,543 repeated measures). Lower maternal education was associated with more adverse levels of several atherogenic lipids and key metabolic traits among females at age 7 years, but not males. For instance, SII for very small very-low-density lipoprotein (VLDL) concentrations was 0.16SD (95% CI: 0.01, 0.30) among females and -0.02SD (95% CI: -0.16, 0.13) among males. Between 7 and 25 years, inequalities widened among females and emerged among males particularly for VLDL particle concentrations, apolipoprotein-B concentrations, and inflammatory glycoprotein acetyls. For instance, at 25 years, SII for very small VLDL concentrations was 0.36SD (95% CI: 0.20, 0.52) and 0.22SD (95% CI: 0.04, 0.40) among females and males respectively. INTERPRETATION: Prevention of socioeconomic inequalities in cardiovascular disease risk requires a life course approach beginning at the earliest opportunity, especially among females. FUNDING: The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). KON is supported by a Health Research Board (HRB) of Ireland Investigator Led Award (ILP-PHR-2022-008). JB, GDS and KT work in a unit funded by the UK MRC (MC_UU_00011/1 and MC UU 00011/3) and the University of Bristol. OR is supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). These funding sources had no role in the design and conduct of this study. This publication is the work of the authors and KON will serve as guarantor for the contents of this paper.

Implementing an integrated diabetic foot care programme in Ireland: podiatrists' experience.

BACKGROUND: International evidence suggests that an integrated multidisciplinary approach to diabetic foot management is necessary to prevent ulceration and progression to amputation. Many health systems have introduced policies or models of care supporting the introduction of this evidence into practice, but little is known about the experiences of those involved in implementation. This study addresses this gap by examining the experiences of podiatrists providing integrated diabetic foot care. METHODS: Between October 2017 and April 2018, an online survey comprising closed and open-ended questions on podiatrists' demographics, clinical activity, links with other services, continuous professional development activities and experiences of implementing the Model of Care was administered to podiatrists (n = 73) working for Ireland's Health Service Executive in the community and hospital setting. Data were analysed using descriptive statistics and qualitative content analysis. RESULTS: The response rate was 68% (n = 50), with 46% (n = 23), 38% (n = 19) and 16% (n = 8) working across hospital, community and both settings, respectively. Most reported treating high-risk patients (66%), those with active foot disease (61%) and educating people about the risk of diabetes to the lower limb (80%). Reported challenges towards integrated diabetic foot care include a perceived lack of awareness of the role of podiatry amongst other healthcare professionals, poor integration between hospital and community podiatry services, especially where new services had been developed, and insufficient number of podiatrists to meet service demands. CONCLUSION: Previous evidence has shown that there is often a gap between what is set out by a policy and what it looks like when delivered to service users. Results from the current study support this, highlighting that while most podiatrists work in line with national recommendations, there are specific gaps and challenges that need to be addressed to ensure successful policy implementation.

Healthcare experiences of patients with Down syndrome from primarily Spanish-speaking households.

We report on the health care experiences of individuals with Down syndrome (DS) from families who are primarily Spanish-speaking. Data were collected through three methods: (1) a nationally distributed, 20-item survey, (2) two focus groups with seven family caregivers of individuals with DS who self-identified as living in primarily Spanish speaking households, and (3) 20 interviews with primary care providers (PCPs) who care for patients who are underrepresented minorities. Standard summary statistics were used to analyze the quantitative survey results. Focus group and interview transcripts, as well as an open-ended response question in the survey, were analyzed using qualitative coding methods to identify key themes. Both caregivers and PCPs described how language barriers make giving and receiving quality care difficult. Caregivers additionally described condescending, discriminatory treatment within the medical system and shared feelings of caregiver stress and social isolation. Challenges to care experienced by families of individuals with DS are compounded for Spanish-speaking families, where the ability to build trust with providers and in the health care system may be compromised by cultural and language differences, systemic issues (lack of time or inability to craft more nuanced schedules so that patients with higher needs are offered more time), mistrust, and sometimes, overt racism. Building this trust is critical to improve access to information, care options, and research opportunities, especially for this community that depends on their clinicians and nonprofit groups as trusted messengers. More study is needed to understand how to better reach out to these communities through primary care clinician networks and nonprofit organizations.

Views on the impact of the COVID-19 pandemic on health in people with Down syndrome from diverse backgrounds.

Down syndrome (DS) has a unique medical and psychological profile. To date, few studies have asked individuals with DS about their views of health, and fewer have explored the impact of COVID-19 on the health of individuals with DS and their families. We used a mixed methods approach including two studies on the health of individuals with DS and their parents conducted during the COVID-19 pandemic: (1) eight virtual focus groups, comprised of 20 parents and 8 individuals with DS to obtain participants' views of health, and (2) a 20-item questionnaire on health care experience of patients with DS who are African American or come from primarily Spanish-speaking homes. Focus group transcripts were coded using a hybrid inductive/deductive framework and thematically analyzed using the Framework Method. This questionnaire included questions regarding the impact of COVID-19 on caregivers and their loved ones with DS; responses to these questions were summarized using descriptive statistics. Individuals with DS discussed the impact of the COVID-19 pandemic on their physical and social health including masking, online learning, and online communication with friends and family. Parents of individuals with DS discussed how the COVID-19 pandemic negatively impacted their child's physical, social, and mental health, as a result of virtual schooling and decreased socialization. There were unexpected positives of the pandemic such as improved hygiene and eased scheduling with telehealth visits. Caregivers noted COVID-19 impacted their own anxiety, employment, and other domains that have potential ripple effects on the health of their children. The COVID-19 pandemic had a pervasive impact on the mental health and wellness of caregivers as well as the physical, social, and mental health of individuals with DS.

Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone in Drosophila.

Ena/VASP proteins are processive actin polymerases that are required throughout animal phylogeny for many morphogenetic processes, including axon growth and guidance. Here we use in vivo live imaging of morphology and actin distribution to determine the role of Ena in promoting the growth of the TSM1 axon of the Drosophila wing. Altering Ena activity causes stalling and misrouting of TSM1. Our data show that Ena has a substantial impact on filopodial morphology in this growth cone but exerts only modest effects on actin distribution. This is in contrast to the main regulator of Ena, Abl tyrosine kinase, which was shown previously to have profound effects on actin and only mild effects on TSM1 growth cone morphology. We interpret these data as suggesting that the primary role of Ena in this axon may be to link actin to the morphogenetic processes of the plasma membrane, rather than to regulate actin organization itself. These data also suggest that a key role of Ena, acting downstream of Abl, may be to maintain consistent organization and reliable evolution of growth cone structure, even as Abl activity varies in response to guidance cues in the environment.

Trends in incidence of ischaemic stroke in people with and without diabetes in Ireland 2005-2015.

AIMS: We aim to describe the epidemiology of ischaemic stroke and in-hospital mortality associated with stroke among men and women with and without diabetes from 2005 to 2015. METHODS: Secondary data analysis of national hospital discharge data from the Hospital Inpatient Enquiry database. Stroke incidence and in-hospital mortality rates in people with and without diabetes were calculated. Poisson regression models were used to estimate the incidence rate ratio (IRR) and assess trends over time. RESULTS: The age-adjusted incidence of stroke was twice as high in people with diabetes compared to those without diabetes (men IRR 2.0 [95% CI 1.95-2.06] and women IRR 2.2 [95% CI 2.12-2.27]). The incidence of ischaemic stroke decreased by an average 1.7% per year in men with diabetes and 3.3% per year in women with diabetes. In people without diabetes, the average annual reduction was smaller (0.2% per year in men and 1% per year in women). In-hospital mortality associated with admission with ischaemic stroke was approximately twice as high in those with diabetes compared to those without diabetes among men [IRR 1.81 (1.67-1.97)] and women [IRR 2 (95% CI 1.84-2.18)]. CONCLUSION: Despite decreases in incidence of ischaemic stroke and associated in-hospital mortality, there remains a twofold increased risk of ischaemic stroke and mortality in people with diabetes. Therefore, priority must be given to management of risk factors for ischaemic stroke in people with diabetes as well as continued development of targeted stroke prevention strategies.

Mitochondrial DNA haplogroups and trajectories of cardiometabolic risk factors during childhood and adolescence: A prospective cohort study.

BACKGROUND: Mitochondria are organelles responsible for converting glucose into energy. Mitochondrial DNA is exclusively maternally inherited. The role of mitochondrial DNA haplogroups in the aetiology of cardiometabolic disease risk is not well understood. METHODS: Sex-specific associations between common European mitochondrial DNA haplogroups (H, U, J, T, K, V, W, I and X) and trajectories of cardiometabolic risk factors from birth to 18 years were examined in a prospective cohort. Cardiometabolic risk factors measured from birth/mid-childhood to 18 years included body mass index (BMI), fat and lean mass, systolic and diastolic blood pressure, pulse rate, high-density lipoprotein cholesterol (HDL-c), non-HDL-c and triglycerides. Fractional polynomial and linear spline multilevel models explored the sex-specific association between haplogroups and risk factor trajectories. RESULTS: Among a total of 7,954 participants with 79,178 repeated measures per outcome, we found no evidence that haplogroups U, T, J, K and W were associated with cardiometabolic risk factors compared to haplogroup H. In females, haplogroup V was associated with 4.0% (99% CI: -7.5, -0.6) lower BMI at age one but associations did not persist at age 18. Haplogroup X was associated with 1.3kg (99% CI: -2.5, -0.2) lower lean mass at age 9 which persisted at 18. Haplogroup V and X were associated with 9.3% (99% CI: -0.4, 19.0) and 16.4% (99% CI: -0.5,33.3) lower fat mass at age 9, respectively, although confidence intervals spanned the null and associations did not persist at 18. In males, haplogroup I was associated with 2.4% (99% CI: -0.5, 5.3) higher BMI at age 7; widening to 5.1% (99% CI: -0.5, 10.6) at 18 with confidence intervals spanning the null. CONCLUSIONS: Our study demonstrated little evidence of sex-specific associations between mitochondrial DNA haplogroups and cardiometabolic risk factors.

Application of multilevel linear spline models for analysis of growth trajectories in a cohort with repeat antenatal and postnatal measures of growth: a prospective cohort study.

OBJECTIVES: To model trajectories of antenatal and postnatal growth using linear spline multilevel models. DESIGN: Prospective cohort study. SETTING: Maternity hospital in Dublin, Ireland. PARTICIPANTS: 720-759 mother-child pairs from the ROLO study (initially a randomised control trial of a low glycaemic index diet in pregnancy to prevent recurrence of macrosomia [birth weight >4 kg]). PRIMARY OUTCOMES: Trajectories of growth from 20 weeks gestation (abdominal circumference [AC], head circumference [HC] and weight) or birth (length/height) to 5 years. RESULTS: Over 50% of women had third-level education and 90% were of white ethnicity. Women were a mean (SD) age of 32 years (4.2) at recruitment. The best fitting model for AC, HC and weight included a model with 5 linear spline periods. The best fitting models for length/height included a model with 3 linear spline periods from birth to 6 months, 6 months to 2 years and 2 years to 5 years. Comparison of observed and predicted values for each model demonstrated good model fit. For all growth measures, growth rates were generally fastest in pregnancy or immediately post partum (for length/height), with rates of growth slowing after birth and becoming slower still as infancy and childhood progressed. CONCLUSION: We demonstrate the application of multilevel linear spline models for examining growth trajectories when both antenatal and postnatal measures of growth are available. The approach may be useful for cohort studies or randomised control trials with repeat prospective assessments of growth.

Decoding Natural Astrocyte Rhythms: Dynamic Actin Waves Result from Environmental Sensing by Primary Rodent Astrocytes.

Astrocytes are key regulators of brain homeostasis, equilibrating ion, water, and neurotransmitter concentrations and maintaining essential conditions for proper cognitive function. Recently, it has been shown that the excitability of the actin cytoskeleton manifests in second-scale dynamic fluctuations and acts as a sensor of chemophysical environmental cues. However, it is not known whether the cytoskeleton is excitable in astrocytes and how the homeostatic function of astrocytes is linked to the dynamics of the cytoskeleton. Here it is shown that homeostatic regulation involves the excitable dynamics of actin in certain subcellular regions of astrocytes, especially near the cell boundary. The results further indicate that actin dynamics concentrate into "hotspot" regions that selectively respond to certain chemophysical stimuli, specifically the homeostatic challenges of ion or water concentration increases. Substrate topography makes the actin dynamics of astrocytes weaker. Super-resolution images demonstrate that surface topography is also associated with the predominant perpendicular alignment of actin filaments near the cell boundary, whereas flat substrates result in an actin cortex mainly parallel to the cell boundary. Additionally, coculture with neurons increases both the probability of actin dynamics and the strength of hotspots. The excitable systems character of actin thus makes astrocytes direct participants in neural cell network dynamics.

Healthcare experiences of patients with Down syndrome who are Black, African American, of African descent, or of mixed race.

Scant research has explored the healthcare experiences of people with Down syndrome (DS) in the United States who are Black, African American, of African descent, or of mixed race. The purpose of this study was to identify and describe the barriers and facilitators that such patients and their caregivers face when accessing healthcare. We gathered data in three ways: focus groups with caregivers, a national survey completed by caregivers, and in-depth interviews with primary care providers. Many caregivers and primary care physicians felt that patients with DS who are Black, African American, of African descent, or of mixed race receive a lower quality of medical care than their white counterparts with DS. Caregivers mentioned feeling tired of being reminded by the medical community about their race and wanting acknowledgment that raising a child with DS can be hard at times. Many felt that the medical community's conscious and unconscious racial biases do negatively impact the care of their loved ones with DS. Caregivers desired more race concordant medical providers or, when not possible, medical providers who are willing to learn more about DS and build trusted, longitudinal relationships. Primary care providers discussed the need for funded resources and support services to effectively care for their patients with DS.

Associations between maternal metabolic parameters during pregnancy and fetal and child growth trajectories from 20 weeks' gestation to 5 years of age: Secondary analysis from the ROLO longitudinal birth cohort study.

OBJECTIVE: To examine the association between maternal metabolic parameters in pregnancy and growth trajectories up to 5 years of age. METHODS: Data from mother-child pairs who participated in the ROLO study, a randomized trial examining the impact of a low glycaemic index diet on the recurrence of macrosomia, were analysed. Fetal and child growth trajectories were developed from longitudinal measurements from 20 weeks gestation up to 5 years of age. We examined associations between maternal fasting glucose, insulin, HOMA-IR and leptin, taken in early pregnancy (14-16 weeks) and late pregnancy (28 weeks), and weight (kg) and abdominal circumference (cm) trajectories using linear spline multilevel models. RESULTS: We found no strong evidence of associations between any maternal metabolic parameters and fetal to childhood weight and abdominal circumference trajectories from 20 weeks gestation to 5 years. CONCLUSION: In a cohort of women with obesity with infants at risk of macrosomia, maternal metabolic markers were not strongly associated with trajectories of weight or abdominal circumference from 20 weeks gestation to 5 years of age.

YOUTH GANGS AND VICTIMIZATION: AN INVESTIGATION OF THE IMPACT OF GANG DYNAMICS ON EXPERIENCES OF VICTIMIZATION.

Studies comparing gang members to similarly situated non-gang members find youth gang involvement is positively associated with experiencing simple and aggravated assault (i.e., violent victimization). This study expands on those studies by using data on gang dynamics from the Denver Youth Survey and bringing theory and concepts directly related to street gangs to the analysis of the relationship between gang membership and different forms of victimization. We focus on specific mechanisms-such as gang organization, centrality, leadership roles, identity, and tenure-that inform gang member behaviors while controlling for risky behaviors and personal histories. Findings indicate (1) gang organization is positively associated with both simple and aggravated assault victimization; (2) gang centrality is positively associated with aggravated assault victimization; and (3) being the leader of a gang is negatively associated with aggravated assault victimization. We discuss the implications of these results using a gang-informed framework.

Adoption and Initial Implementation of a National Integrated Care Programme for Diabetes: A Realist Evaluation.

Background: The implementation of models of integrated care for chronic conditions is not well understood. We conducted a realist evaluation to determine how and why the implementation of the National Diabetes Programme in Ireland worked (or not). Methods: Documentary analysis and qualitative interviews with a purposive sample of national stakeholders (n = 19), were used to develop an initial theory on expected programme delivery. We refined this theory using semi-structured interviews (n = 38) with professionals from different clinical disciplines involved in programme implementation. Results: Locally important contexts facilitating implementation included staff experience of delivering diabetes care, capacity, and familiarity with the intended purpose of new clinical posts. The extent to which integrated care was adopted and implemented depended on judgements made by professionals working in these contexts; specifically, judging the relative advantage of the programme and whether to engage in negotiations to legitimize their new roles in diabetes care. Conclusions: Our results highlight the need for adequate preparatory work to raise awareness of and support new roles to implement integrated care, clarification on the core components of new care models, and the development of local service infrastructures to support integrated care.

Evaluating Food Packaging Waste in Schools: A Systematic Literature Review.

Public schools in the U.S. generate about 14,500 tons of municipal solid waste daily, and approximately 42% of that is food packaging generated by school foodservice, contributing significantly to the global packaging waste crisis. This literature review summarizes methods used to evaluate food packaging waste in school foodservice. This review has two objectives: first, to understand which methodologies currently exist to evaluate food packaging waste generation and disposal in school foodservice; and second, to describe the creation of and share a practical standardized instrument to evaluate food packaging waste generation and disposal in school foodservice. A systematic review was conducted using the following search terms: solid waste, school, cafeteria and food packaging, waste, and school. The final review included 24 studies conducted in school environments (kindergarten through twelfth grade or college/university), 16 of which took place in the U.S. Food packaging waste evaluations included objective methods of waste audits, models, and secondary data as well as subjective methods of qualitative observations, questionnaires, interviews, and focus groups. Large variation exists in the settings, participants, designs, and methodologies for evaluating school foodservice packaging waste. Lack of standardization was observed even within each methodology (e.g., waste audit). A new instrument is proposed to support comprehensive and replicable data collection, to further the understanding of school foodservice food packaging waste in the U.S., and to reduce environmental harms.

Debtors' Blocks: How Monetary Sanctions Make Between-neighborhood Racial and Economic Inequalities Worse.

Although recent scholarship has enumerated many individual-level consequences of criminal legal citations and sentences involving fines and fees, we know surprisingly little about the structural consequences of monetary sanctions or legal financial obligations (LFOs). We use social disorganization and critical race theories to examine neighborhood-level associations between and among LFO sentence amounts, poverty, and racial and ethnic demographics. Using longitudinal data from the Washington State Administrative Office of the Courts, and the American Community Survey, we find LFOs are more burdensome in high-poverty communities and of color, and that per-capita rates of LFOs sentenced are associated with increased future poverty rates across all neighborhoods.

Puberty Timing and Sex-Specific Trajectories of Systolic Blood Pressure: a Prospective Cohort Study.

BACKGROUND: Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP preceding and following puberty and examined the impact of puberty timing on SBP trajectories in females and males. METHODS: Trajectories of SBP before and after puberty and by timing of puberty in females and males in a contemporary birth cohort study were analyzed. Repeated measures of height from age 5 to 20 years were used to identify puberty timing (age at peak height velocity). SBP was measured on ten occasions from 3 to 24 years (N participants, 4062; repeated SBP measures, 29 172). Analyses were performed using linear spline multilevel models based on time before and after puberty and were adjusted for parental factors and early childhood factors. RESULTS: Mean age at peak height velocity was 11.7 years (SD, 0.8) for females and 13.6 years (SD, 0.9) for males. Males had faster rates of increase in SBP before puberty leading to 10.19 mm Hg (95% CI, 6.80-13.57) higher mean SBP at puberty which remained similar at 24 years (mean difference, 11.43 mm Hg [95% CI, 7.22-15.63]). Puberty timing was associated with small transient differences in SBP trajectories postpuberty in both sexes and small differences at 24 years in females only. CONCLUSIONS: A large proportion of the higher SBP observed in males compared with females in early adulthood is accrued before puberty. Interventions targeting puberty timing are unlikely to influence SBP in early adulthood.

Sex-specific associations of adiposity with cardiometabolic traits in the UK: A multi-life stage cohort study with repeat metabolomics.

BACKGROUND: Sex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages. METHODS AND FINDINGS: Data were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B-containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required. CONCLUSIONS: The results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

Maternal prenatal anxiety and depression and trajectories of cardiometabolic risk factors across childhood and adolescence: a prospective cohort study.

OBJECTIVES: Quantifying long-term offspring cardiometabolic health risks associated with maternal prenatal anxiety and depression can guide cardiometabolic risk prevention. This study examines associations between maternal prenatal anxiety and depression, and offspring cardiometabolic risk from birth to 18 years. DESIGN: This study uses data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. PARTICIPANTS: Participants were 526-8606 mother-offspring pairs from the ALSPAC cohort. SETTING: British birth cohort set, Bristol, UK. PRIMARY AND SECONDARY OUTCOMES: Exposures were anxiety (Crown-Crisp Inventory score) and depression (Edinburgh Postnatal Depression Scale score) measured at 18 and 32 weeks gestation. Outcomes were trajectories of offspring body mass index; fat mass; lean mass; pulse rate; glucose, diastolic and systolic blood pressure (SBP); triglycerides, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and insulin from birth/early childhood to 18 years. Exposures were analysed categorically using clinically relevant, cut-offs and continuously to examine associations across the distribution of prenatal anxiety and depression. RESULTS: We found no strong evidence of associations between maternal anxiety and depression and offspring trajectories of cardiometabolic risk factors. Depression at 18 weeks was associated with higher SBP at age 18 (1.62 mm Hg (95% CI 0.17 to 3.07). Anxiety at 18 weeks was also associated with higher diastolic blood pressure at 7 years in unadjusted analyses (0.70 mm Hg (95% CI 0.02 to 1.38)); this difference persisted at age 18 years (difference at 18 years; 0.89 mm Hg (95% CI 0.05 to 1.73). No associations were observed for body mass index; fat mass; lean mass; pulse rate; glucose; triglycerides, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and insulin. CONCLUSIONS: This is the first examination of maternal prenatal anxiety and depression and trajectories of offspring cardiometabolic risk. Our findings suggest that prevention of maternal prenatal anxiety and depression may have limited impact on offspring cardiometabolic health across the first two decades of life.