Sex-stratified Models Research Articles

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies

BackgroundExposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. ObjectiveTo investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. MethodsIn 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. ResultsThe LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): −2.8 (−4.2;-0.4); MEHP: −1.4 (−3.4,0.2)] and higher FSH [∑DINP: 11.8 (−0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [−4.28 (−8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: −12.22 (−21.09;-1.18); oxo-MEHP: −12.73 (−22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. ConclusionWe observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

An X Chromosome Transcriptome Wide Association Study Implicates ARMCX6 in Alzheimer's Disease.

The X chromosome is often omitted in disease association studies despite containing thousands of genes that may provide insight into well-known sex differences in the risk of Alzheimer's disease (AD). To model the expression of X chromosome genes and evaluate their impact on AD risk in a sex-stratified manner. Using elastic net, we evaluated multiple modeling strategies in a set of 175 whole blood samples and 126 brain cortex samples, with whole genome sequencing and RNA-seq data. SNPs (MAF > 0.05) within the cis-regulatory window were used to train tissue-specific models of each gene. We apply the best models in both tissues to sex-stratified summary statistics from a meta-analysis of Alzheimer's Disease Genetics Consortium (ADGC) studies to identify AD-related genes on the X chromosome. Across different model parameters, sample sex, and tissue types, we modeled the expression of 217 genes (95 genes in blood and 135 genes in brain cortex). The average model R2 was 0.12 (range from 0.03 to 0.34). We also compared sex-stratified and sex-combined models on the X chromosome. We further investigated genes that escaped X chromosome inactivation (XCI) to determine if their genetic regulation patterns were distinct. We found ten genes associated with AD at p < 0.05, with only ARMCX6 in female brain cortex (p=0.008) nearing the significance threshold after adjusting for multiple testing (α=0.002). We optimized the expression prediction of X chromosome genes, applied these models to sex-stratified AD GWAS summary statistics, and identified one putative AD risk gene, ARMCX6.

Longitudinal associations of screen time, physical activity, and sleep duration with body mass index in U.S. youth

BackgroundYouth use different forms of screen time (e.g., streaming, gaming) that may be related to body mass index (BMI). Screen time is non-independent from other behaviors, including physical activity and sleep duration. Statistical approaches such as isotemporal substitution or compositional data analysis (CoDA) can model associations between these non-independent behaviors and health outcomes. Few studies have examined different types of screen time, physical activity, and sleep duration simultaneously in relation to BMI.MethodsData were baseline (2017–2018) and one-year follow-up (2018–2019) from the Adolescent Brain Cognitive Development Study, a multi-site study of a nationally representative sample of U.S. youth (N = 10,544, mean [SE] baseline age = 9.9 [0.03] years, 48.9% female, 45.4% non-White). Participants reported daily minutes of screen time (streaming, gaming, socializing), physical activity, and sleep. Sex-stratified models estimated the association between baseline behaviors and follow-up BMI z-score, controlling for demographic characteristics, internalizing symptoms, and BMI z-score at baseline.ResultsIn females, isotemporal substitution models estimated that replacing 30 min of socializing (β [95% CI] = -0.03 [-0.05, -0.002]), streaming (-0.03 [-0.05, -0.01]), or gaming (-0.03 [-0.06, -0.01]) with 30 min of physical activity was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing (-0.03 [-0.05, -0.01]), streaming (-0.02 [-0.03, -0.01]), or gaming (-0.02 [-0.03, -0.01]) with 30 min of sleep was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing with 30 min of gaming was associated with a lower follow-up BMI z-score (-0.01 [-0.03, -0.0001]). CoDA estimated that in males, a greater proportion of time spent in baseline socializing, relative to the remaining behaviors, was associated with a higher follow-up BMI z-score (0.05 [0.02, 0.08]). In females, no associations between screen time and BMI were observed using CoDA.ConclusionsOne-year longitudinal associations between screen time and BMI may depend on form of screen time, what behavior it replaces (physical activity or sleep), and participant sex. The alternative statistical approaches yielded somewhat different results. Experimental manipulation of screen time and investigation of biopsychosocial mechanisms underlying the observed sex differences will allow for causal inference and can inform interventions.

Body surface scan anthropometrics are associated with grip strength in the general population

Background and aimBody shape and anthropometrics are well-known risk factors for cardiovascular diseases (CVD) and mortality. Hand-grip strength (HGS) is also a meaningful marker of health and a promising predictor of CVD and mortality. There is a lack of studies that have systematically investigated associations between body shape and anthropometrics with HGS. In a population-based study, we investigated if anthropometric markers derived from 3D body scanning are related to HGS. Methods and resultsWe used the data of 1,599 individuals aged 36 to 93 years, who participated in the Study of Health in Pomerania. A total of 87 anthropometric markers, determined by a 3D body scanner, were included in the analysis. Anthropometric measurements were standardized and used as exposure variables. HGS was measured with a hand dynamometer and used as outcome. Sex-stratified linear regression models adjusted for age and height were used to relate standardized anthropometrics and HGS. Anthropometric markers were ranked according to -log-p-values.In men, left and right forearm circumference, left arm length to neck (C7), left forearm length, and forearm-fingertip length were most strongly related to HGS. In women, right forearm circumference, forearm-fingertip length, shoulder breadth, left forearm circumference, and right wrist circumference showed the most significant associations with HGS. The final prediction models contained 13 anthropometric markers in males (R2=0.54) and eight anthropometric markers in females (R2=0.37). ConclusionsThe identified parameters may help estimate HGS in the clinical setting. However, studies in clinical settings are essential to validating our findings.

Socioeconomic position indicators and risk of alcohol-related medical conditions: A national cohort study from Sweden.

Alcohol consumption contributes to excess morbidity and mortality in part through the development of alcohol-related medical conditions (AMCs, including alcoholic cardiomyopathy, hepatitis, cirrhosis, etc.). The current study aimed to clarify the extent to which risk for these outcomes differs as a function of socioeconomic position (SEP), as discrepancies could lead to exacerbated health disparities. We used longitudinal Swedish national registries to estimate the individual and joint associations between 2 SEP indicators, educational attainment and income level, and risk of AMC based on International Classification of Diseases codes, while controlling for other sociodemographic covariates and psychiatric illness. We conducted Cox proportional hazards models in sex-stratified analyses (N = 1,162,679 females and N = 1,196,659 males), beginning observation at age 40 with follow-up through December 2018, death, or emigration. By the end of follow-up, 4,253 (0.37%) females and 11,183 (0.93%) males had received an AMC registration, corresponding to overall AMC incidence rates among females and males of 2.01 and 5.20, respectively. In sex-stratified models adjusted for birth year, marital status, region of origin, internalizing and externalizing disorder registrations, and alcohol use disorder (AUD) registration, lower educational attainment was associated with higher risk of AMC in both females (hazard ratios [HRs] = 1.40 to 2.46 for low- and mid-level educational attainment across 0 to 15 years of observation) and males (HRs = 1.13 to 1.48). Likewise, risk of AMC was increased for those with lower income levels (females: HRs = 1.10 to 5.86; males: HRs = 1.07 to 6.41). In secondary analyses, we further adjusted for aggregate familial risk of AUD by including family genetic risk scores for AUD (FGRSAUD), estimated using medical, pharmacy, and criminal registries in extended families, as covariates. While FGRSAUD were associated with risk of AMC in adjusted models (HR = 1.17 for females and HR = 1.21 for males), estimates for education and income level remained largely unchanged. Furthermore, FGRSAUD interacted with income level, but not education level, such that those at higher familial liability to AUD were more susceptible to the adverse effect of low income. Limitations of these analyses include the possibility of false negatives for psychiatric illness registrations, changes in income after age 40 that were not accounted for due to modeling restrictions, restriction to residents of a high-income country, and the inability to account for individual-level alcohol consumption using registry data. Using comprehensive national registry data, these analyses demonstrate that individuals with lower levels of education and/or income are at higher risk of developing AMC. These associations persist even when accounting for a range of sociodemographic, psychiatric, and familial risk factors. Differences in risk could contribute to further health disparities, potentially warranting increased screening and prevention efforts in clinical and public health settings.

Lifecourse correlates of self-rated health and associations with subsequent mortality: findings from the Hertfordshire Cohort Study

BackgroundPoor self-rated health (SRH) has been shown to predict adverse health outcomes among older people, however these associations have traditionally only been considered at one point in the lifecourse, usually midlife or later. Here we examined lifecourse correlates of SRH in early, mid and later life, relating these to subsequent risk of mortality in a community-dwelling cohort. Methods2989 men and women from the Hertfordshire Cohort Study (HCS) were included in this study. The HCS was initially retrospective and linked contemporary health outcome data to early life data available from health ledgers but investigations from baseline (1998–2004, aged 59–73) onwards have been prospective. At baseline, participants completed an initial clinic visit, which included questionnaire assessment of SRH, reported as 'excellent', 'very good', 'good', 'fair', or 'poor'. Socioeconomic, lifestyle, mental health and demographic information was also collected. Deaths were recorded from baseline to 31/12/2018. Baseline characteristics in relation to SRH were examined using sex-stratified ordinal logistic regression; these factors were examined in relation to mortality using sex-stratified Cox regression. Statistically significant exposures were then included in sex-stratified mutually-adjusted models. ResultsIn mutually-adjusted analysis, numerous contemporaneous correlates of poorer SRH in the seventh decade were identified and included obesity, lower physical activity, greater comorbidity and higher levels of depression among men and women. For example, odds ratios for being in a lower category of SRH were as follows: obese (BMI≥30) vs underweight/healthy (BMI<25) (men 1.60 (1.21, 2.11), women 1.65 (1.25, 2.17)) and per additional system medicated (men 1.62 (1.47, 1.77), women 1.53 (1.41, 1.66)). By contrast, factors earlier in the lifecourse (early growth, age left full-time education) were not associated with SRH in late adulthood. 36% of men and 26% of women died during follow-up. Hazard ratios (95% CI) for mortality per lower category of SRH were 1.22 (1.10,1.36) among men and 1.17 (1.01,1.35) among women after adjustment for age, BMI, smoking, physical activity, diet quality, education, home ownership status, comorbidity level and depression levels, suggesting residual confounding by other unrecorded factors that are related to SRH. ConclusionsPoorer SRH in the seventh decade was a risk factor for mortality. Importantly modifiable adverse health behaviours in the seventh decade, such as low physical activity, were associated with poorer SRH and later mortality after adjustment for socioeconomic factors and comorbidity level. By contrast early growth and education were not related to later SRH. These data suggest that attention to lifestyle in late midlife may be associated with better SRH and subsequent health outcomes, highlighting the value of intervention at this stage of the lifecourse.

Sex-based trajectories of health system use in lonely and not lonely older people: A population-based cohort study.

There is growing interest in understanding the care needs of lonely people but studies are limited and examine healthcare settings separately. We estimated and compared healthcare trajectories in lonely and not lonely older female and male respondents to a national health survey. We conducted a retrospective cohort study of community-dwelling, Ontario respondents (65+ years) to the 2008/2009 Canadian Community Health Survey-Healthy Aging. Respondents were classified at baseline as not lonely, moderately lonely, or severely lonely using the Three-Item Loneliness Scale and then linked with health administrative data to assess healthcare transitions over a 12 -year observation period. Annual risks of moving from the community to inpatient, long-stay home care, long-term care settings-and death-were estimated across loneliness levels using sex-stratified multistate models. Of 2684 respondents (58.8% female sex; mean age 77 years [standard deviation: 8]), 635 (23.7%) experienced moderate loneliness and 420 (15.6%) severe loneliness. Fewer lonely respondents remained in the community with no transitions (not lonely, 20.3%; moderately lonely, 17.5%; and severely lonely, 12.6%). Annual transition risks from the community to home care and long-term care were higher in female respondents and increased with loneliness severity for both sexes (e.g., 2-year home care risk: 6.1% [95% CI 5.5-6.6], 8.4% [95% CI 7.4-9.5] and 9.4% [95% CI 8.2-10.9] in female respondents, and 3.5% [95% CI 3.1-3.9], 5.0% [95% CI 4.0-6.0], and 5.4% [95% CI 4.0-6.8] in male respondents; 5-year long-term care risk: 9.2% [95% CI 8.0-10.8], 11.1% [95% CI 9.3-13.6] and 12.2% [95% CI 9.9-15.3] [female], and 5.3% [95% CI 4.2-6.7], 9.1% [95% CI 6.8-12.5], and 10.9% [95% CI 7.9-16.3] [male]). Lonely older female and male respondents were more likely to need home care and long-term care, with severely lonely female respondents having the highest probability of moving to these settings.

Discrimination, Smoking, and Cardiovascular Disease Risk: A Moderated Mediation Analysis With MESA.

Carotid intima-media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular disease risk, and research highlights that racial and ethnic minority individuals generally exhibit higher cIMT and carotid plaque than White individuals. At present, the mechanisms driving these disparities among different racial and ethnic and biological sex groups are poorly understood. Data came from the baseline examination of MESA (Multi-Ethnic Study of Atherosclerosis). A total of 6814 participants aged 45 to 84 years free of clinical cardiovascular disease completed assessments on health behavior and perceived discrimination. Four sex-stratified moderated mediation models examined associations between discrimination, cigarette smoking, and mean cIMT and plaque. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features, and that these would differ by race and ethnicity. Indirect effects of discrimination on plaque were observed among Hispanic women such that discrimination was associated with cigarette use and, in turn, higher plaque (β=0.04 [95% CI, 0.01-0.08]). Indirect effects of discrimination on mean cIMT were found among Hispanic (β=0.003 [95% CI, 0.0001-0.007]) and White men (β=0.04 [95% CI, 0.01-0.08]) such that discrimination was associated with cigarette use and, in turn, higher cIMT. Finally, a positive indirect effect of discrimination on plaque was observed among Hispanic men (β=0.03 [95% CI, 0.004-0.07]). No other racial and ethnic differences were observed. To understand and address social determinants of cardiovascular disease, researchers must incorporate an intersectional framework that will allow us to understand the complex nature of discrimination and cardiovascular disease risk for individuals of varying intersecting identities and social positions.

Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi-Ethnic Study of Atherosclerosis.

Muscle density is inversely associated with all-cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women. Adult participants (N=1869) in the Multi-Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2-L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm2. Sex-stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex-specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow-up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (P trend=0.15). However, there was an inverse association between density and CHD (P trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (P trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile; P trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile; P trend<0.001), and null for stroke (P trend=0.67). Associations for women were mostly null. For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.

Abstract HUP6: Ideal Cardiovascular Health and the Intersectionality of Race/Ethnicity and Sexual Identity

Introduction: Disparities exist in cardiovascular health (CVH) by sexual identity and race/ethnicity separately, however an understanding of the intersectional effect of these identities has been limited. Objective: To evaluate differences in ideal CVH, as captured in the American Heart Association’s Life’s Essential 8 framework, across race/ethnicity and sexual identity. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES, 2007-2016). Non-institutionalized adults (18-59 years) without a history of cardiovascular disease/stroke and who were not pregnant at the time of the interview were included. Self-reported race/ethnicity was categorized as non-Hispanic Black (hereafter Black), Hispanic, non-Hispanic White (hereafter White), and another race. Self-reported sexual identity was categorized as straight and sexual minority (SM), which encompassed those who identified as lesbian, gay, bisexual, or something else. The primary outcome was total CVH score (range 0 -100), which is the unweighted average of 8 CVH components, assessed using questionnaire, dietary, and physical examination data. Sex-stratified regression models were developed for the overall CVH score and CVH components, adjusting for age and study year. Results: The sample included 12,256 adults (mean age 39.6 years [SD 11.7]). While Black (ß= -4.9, 95% CI -7.7, -2.0), Hispanic (ß= -4.9, 95% CI -9.6, -0.2), and White (ß = -5.9, 95% CI -8.8, -3.0) SM female adults had lower total CVH scores compared to their straight counterparts, female participants of another race and SM male adults of any race/ethnicity did not. Black SM female individuals had less favorable nicotine (ß= -20.9, 95% CI -32.3, -9.4) and blood pressure (ß= -7.2, 95% CI -13.8, -0.6) scores compared with Black straight females. Hispanic SM female individuals had less favorable body mass index scores (ß= -15.6, 95% CI -28.0, -3.2) compared with Hispanic straight females. Conclusions: CVH differed across racial/ethnic identities in SM females but not SM males. Longitudinal studies are needed to identify mechanisms driving CVH disparities in Black and Hispanic SM females.

The impact of the COVID-19 pandemic on rates of adolescents receiving psychopharmacological medication in Austria

BackgroundThe COVID-19 pandemic has impacted many aspects of everyday life, including the (mental) healthcare system. An increase in depression and anxiety symptoms has been reported worldwide, and is particularly pronounced in females and young people. We aimed to evaluate changes in prescription rates for psychopharmacological medication, which is often used to treat depression and anxiety.MethodBased on data from the Austrian public health insurance institutions, we conducted an interrupted time series analysis of antidepressants and antipsychotics, comparing prescription rate developments before and throughout the COVID-19 pandemic (2013 to 2021), with a special focus on adolescents (10–19 years) in comparison to the general population. Data were based on all public prescriptions in the outpatient sector nationwide. Age- and sex-stratified time-series models were fitted to the pre-COVID period (first quarter (Q1) of 2013 to second quarter (Q2) of 2020). These were used to generate forecasts for the period from the third quarter (Q3) of 2020 to the fourth quarter (Q4) of 2021, which were subsequently compared to observed developments in order to assess significant deviations from the forecasted development paths.ResultsFor the majority of the evaluated period, we found a significant excess of antidepressant prescriptions among both male and female adolescents (10–14 and 15–19 years) compared to the forecasted development path, while the general population was mostly within 97.5% confidence intervals of the forecasts. Regarding antipsychotics, the interrupted time series analysis revealed a significant excess in the group of female adolescents in almost all quarters, which was especially pronounced in the 15–19 age group. Prescription rates of antipsychotics in the general population only showed a significant excess in two quarters.ConclusionIncreased rates of adolescents receiving psychopharmacological treatment echo the epidemiological trends of an increase in depression and anxiety symptoms reported in the literature. This increase is especially pronounced in female adolescents.

Total and temporal patterning of physical activity in adolescents and associations with mental wellbeing

BackgroundThere is limited understanding of the extent to which differences in physical activity across the day and week may be associated with mental wellbeing. Such an understanding is needed for better targeting of interventions. In this study, we describe total and temporal patterning of physical activity across the week in adolescents (age 13-14y) and assess their prospective associations with mental wellbeing.Methods1,983 13-14-year-old adolescent participants based in Cambridgeshire and Essex, recruited between 2016 and 2017 into the Get Others Active Trial provided data at baseline and 4 months. Physical activity was measured at baseline using wrist-worn accelerometers across different time segments (whole week, weekday schooltime, weekday out of school, and weekend), and operationalized as average movement-related acceleration for each time segment. Mental Wellbeing at baseline and 4 months was measured using the Warwick Edinburgh MentalWellbeing Scale. Associations between physical activity across different time segments (whole week, weekday schooltime, weekday out of school, and weekend) and mental wellbeing at 4 months were investigated using sex-stratified multi-level regression models, adjusted for covariates, and both adjusted and unadjusted for baseline mental wellbeing.ResultsOur analyses found positive associations between physical activity and mental wellbeing at 4 months, unadjusted for baseline wellbeing. Among girls, positive associations were shown when considering physical activity across the whole week 0.07 (95% CI, 0.03–0.12), and across all separate time periods studied: weekday schooltime 0.07 (95% CI, 0.02–0.11), weekday out-of-school time 0.07 (95% CI, 0.03–0.12), and weekend 0.07 (95% CI, 0.02–0.11). For boys, similar associations were observed for activity across the week 0.07 (95% CI, 0.03–0.11), during weekday schooltime 0.08 (95% CI, 0.04–0.12), and weekday out-of-school time 0.07 (95% CI, 0.03–0.11), but not the weekend 0.01 (95% CI, -0.03-0.05). For both girls and boys, associations were attenuated below significance after adjusting for baseline wellbeing.ConclusionsThis longitudinal analysis showed positive associations between physical activity and later mental wellbeing in both male and female adolescents across most time segments. Higher physical activity throughout the week may be associated with better mental wellbeing in the adolescent population. Further research is required to understand determinants of change in wellbeing over time.Trial RegistrationRegistration Number: ISRCTN31583496. Registered: 18/02/2014.

In Utero Exposure to Alcohol and Tobacco and Electroencephalogram Power During Childhood

Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] μV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] μV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] μV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] μV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] μV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] μV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] μV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] μV2; P = .04) power compared with those with no PTE. These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.

Associations between screen viewing at 2 and 3.5 years and drawing ability at 3.5 years among children from the French nationwide Elfe birth cohort

The effect of screen viewing on children’s cognitive development has been of concern among parents and researchers. This study investigated the association between children screen time, as reported by parents, and drawing ability, and the confounding effects of socioeconomic characteristics (such as parental education, household income, migration status) and children’s competing activities (such as drawing practice, extracurricular activity, outdoor time, sleep time, time playing with parents). Participants included 7577 children aged 3.5 years (50% girls) who underwent the Draw-a-person test (McCarthy score [range = 0–12 points]) in the French nationwide Elfe birth cohort, initiated in 2011. Sex-stratified zero-inflated Poisson regression models were used. Increased screen time was associated with a higher likelihood to obtain a null score in boys (OR 1.15, 95% CI 1.07–1.23) and girls (1.13 [1.03–1.24]) and a lower score in girls only (β = − 0.02, 95% CI − 0.04; − 0.01). After adjusting for SES, associations were no longer observed, indicating that the association between screen time and drawing abilities was confounded by socioeconomic characteristics.

Prenatal and childhood lead exposure is prospectively associated with biological markers of aging in adolescence

Few studies have related early life lead exposure to adolescent biological aging, a period characterized by marked increases in maturational tempo. We examined associations between prenatal and childhood lead exposure and adolescent biological age (mean 14.5 years) utilizing multiple epigenetic clocks including: intrinsic (IEAA), extrinsic (EEAA), Horvath, Hannum, PhenoAge, GrimAge, Skin-Blood, Wu, PedBE, as well as DNA methylation derived telomere length (DNAmTL). Epigenetic clocks and DNAmTL were calculated via adolescent blood DNA methylation measured by Infinium MethylationEPIC BeadChips. We constructed general linear models (GLMs) with individual lead measures predicting biological age. We additionally examined sex-stratified models and lead by sex interactions, adjusting for adolescent age and lead levels, maternal smoking and education, and proportion of cell types. We also estimated effects of lead exposure on biological age using generalized estimating equations (GEE). First trimester blood lead was positively associated with a 0.14 increase in EEAA age in the GLMs though not the GEE models (95%CI 0.03, 0.25). First and 2nd trimester blood lead levels were associated with a 0.02 year increase in PedBE age in GLM and GEE models (1st trimester, 95%CI 0.004, 0.03; 2nd trimester, 95%CI 0.01, 0.03). Third trimester and 24 month blood lead levels were associated with a −0.06 and −0.05 decrease in Skin-Blood age, respectively, in GLM models. Additionally, 3rd trimester blood lead levels were associated with a 0.08 year decrease in Hannum age in GLM and GEE models (95%CI -0.15, −0.01). There were multiple significant results in sex-stratified models and significant lead by sex interactions, where males experienced accelerated biological age, compared to females who saw a decelerated biological age, with respect to IEAA, EEAA, Horvath, Hannum, and PedBE clocks. Further research is needed to understand sex-specific relationships between lead exposure and measures of biological aging in adolescence and the trajectory of biological aging into young adulthood.

Pressure Pain Sensitivity and Chronotype: A Population-based Study of Middle-aged Finns

Evening chronotype individuals experience pain more often than morning chronotypes, but relationships with pain sensitivity have rarely been studied. We examined whether chronotype is associated with pressure pain sensitivity, with special reference to mental health disorders, insomnia, and chronic musculoskeletal (MSK) pain as potential moderating factors. The study sample consisted of members of the Northern Finland Birth Cohort 1966 aged 46. Pressure pain threshold and tolerance were measured via the standardized protocol, categorized as lowest quartile versus others. Chronotype (morning [M; the reference], intermediate [I], and evening [E]) was defined using the Short Morningness-Eveningness questionnaire. Sex-stratified binary logistic regression models were separately adjusted for education, body mass index, long-term diseases (fully adjusted model), and for mental health disorders, insomnia, and chronic MSK pain (a residual confounding analysis). Interaction terms (Chronotype × Mental health/insomnia/chronic MSK pain) were tested. The study had 2,132 males and 2,830 females. The E-type males had 1.5-fold odds of having a low pain threshold (fully adjusted odds ratio [OR] 1.45, 95% confidence interval 1.05–2.00) and pressure pain tolerance (fully adjusted OR 1.47, 1.07–2.02), in comparison to M-types. Having a mental health disorder intensified the association with low pain threshold fourfold (4.06, 1.56–10.6). Being an E-type female was also associated with a low pain threshold, but the association was statistically nonsignificant (fully adjusted OR 1.18, .90–1.53). No statistically significant interactions were found among females. These results emphasize the role of chronotype in pain sensitivity and add an understanding of pain experience in light of innate circadian types. PerspectiveMale evening chronotypes are more sensitive to pain than morning chronotypes. Diagnosed mental health disorders in particular indicate a low pain threshold for evening chronotype males.

Disentangling associations between pubertal development, healthy activity behaviors, and sex in adolescent social networks.

With the onset of puberty, youth begin to choose their social environments and develop health-promoting habits, making it a vital period to study social and biological factors contextually. An important question is how pubertal development and behaviors such as physical activity and sleep may be differentially linked with youths' friendships. Cross-sectional statistical network models that account for interpersonal dependence were used to estimate associations between three measures of pubertal development and youth friendships at two large US schools drawn from the National Longitudinal Study of Adolescent to Adult Health. Whole-network models suggest that friendships are more likely between youth with similar levels of pubertal development, physical activity, and sleep. Sex-stratified models suggest that girls' friendships are more likely given a similar age at menarche. Attention to similar pubertal timing within friendship groups may offer inclusive opportunities for tailored developmental puberty education in ways that reduce stigma and improve health behaviors.

SOCIOECONOMIC STATUS AND WORKING LIFE EXPECTANCY IN SWEDEN

Abstract Longer life expectancy and fertility decline have increased concerns about the security of old-age pensions. Raising retirement ages is one strategy to offset rising costs, though the option to retire varies considerably by socioeconomic status (SES) and sex. The level of variation in SES may depend the measure used. Also, many workers now transition into retirement slowly, e.g., move from full- to part-time work. Thus, retirement age may not sufficiently capture how long people work. Working life expectancy (WLE)—the expected average number of years worked—better measures total working life. We use data from the Swedish Longitudinal Occupational Survey of Health (SLOSH) from 2008 to 2020 (n=4,940 people age 50+ and n=74,093 person-observations) to examine WLE by SES. We estimate a three-state multistate model (i.e., working, not working, dead) and a four-state model (working part-time, working full-time, not working, and dead); both assume a continuous-time first-order Markov process. Models are sex-stratified models, cross-classified by: 1) occupation; 2) education; 3) income. We find that professionals work full-time 1 year more than routine workers, regardless of sex. The low educated work full-time 1 year less than the highly educated. In our weighted three-state model, where part-time work contributed ½ of full-time work, the difference increased to 1.14 and 1.05 years, respectively. Our unweighted three-state model showed slightly larger education differences. Findings suggest that WLE differs by SES, regardless of sex, and the differences are greater by education than occupation. This has implications for extending working life policies.

Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort

Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (ORfine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males ORfine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.

Geographic Mobility and HIV Care Engagement among People Living with HIV in Rural Kenya and Uganda.

Human mobility is a critical aspect of existence and survival, but may compromise care engagement among people living with HIV (PLHIV). We examined the association between various forms of human mobility with retention in HIV care and antiretroviral treatment (ART) interruptions. In a cohort of adult PLHIV in Kenya and Uganda, we collected surveys in 2016 about past 6-month travel and lifetime migration histories, including reasons and locations, and engagement in HIV care defined as (1) discontinuation of care, and (2) history of a treatment interruption among those who remained in care. We estimated associations between mobility and these care engagement outcomes via logistic regression, adjusted for sex, prior mobility, age, region, marital status, household wealth, and education. Among 1081 participants, 56 (5%) reported having discontinued care; among those in care, 104 (10%) reported treatment interruption. Past-year migration was associated with a higher risk of discontinuation of care (adjusted odds ratio [aOR] 1.98, 95% CI 1.08-3.63). In sex-stratified models, the association was somewhat attenuated in women, but remained robust among men. Past-year migration was associated with reduced odds of having a treatment interruption among men (aOR 0.51, 95% CI 0.34-0.77) but not among women (aOR 2.67, 95% CI 0.78, 9.16). Travel in the past 6 months was not associated with discontinuation of care or treatment interruptions. We observed both negative and protective effects of recent migration on care engagement and ART use that were most pronounced among men in this cohort. Migration can break ties to ongoing care, but for men, who have more agency in the decision to migrate, may foster new care and treatment strategies. Strategies that enable health facilities to support individuals throughout the process of transferring care could alleviate the risk of care disengagement.