Associations of short-term exposure to air pollution and increased ambient temperature with psychiatric hospital admissions in older adults in the USA: a case-crossover study.

BACKGROUND: Little is known about the associations between ambient environmental exposures and the risk of acute episodes of psychiatric disorders. We aimed to estimate the link between short-term exposure to atmospheric pollutants, temperature, and acute psychiatric hospital admissions in adults aged 65 years and older in the USA. METHODS: For this study, we included all people (aged ≥65 years) enrolled in the Medicare programme in the USA who had an emergency or urgent hospital admission for a psychiatric disorder recorded between Jan 31, 2000, and Dec 31, 2016. We applied a case-crossover design to study the associations between short-term exposure to air pollution (fine particulate matter [PM2·5], ozone, and nitrogen dioxide [NO2]), ambient temperature, and the risk of acute hospital admissions for depression, schizophrenia, and bipolar disorder in this population. The percentage change in the risk of hospital admission and annual absolute risk differences were estimated. FINDINGS: For each 5°C increase in short-term exposure to cold season temperature, the relative risk of acute hospital admission increased by 3·66% (95% CI 3·06-4·26) for depression, by 3·03% (2·04-4·02) for schizophrenia, and by 3·52% (2·38-4·68) for bipolar disorder in the US Medicare population. Increased short-term exposure to PM2·5 and NO2 was also associated with a significant increase in the risk of acute hospital admissions for psychiatric disorders. Each 5 µg/m3 increase in PM2·5 was associated with an increase in hospital admission rates of 0·62% (95% CI 0·23-1·02) for depression, 0·77% (0·11-1·44) for schizophrenia, and 1·19% (0·49-1·90) for bipolar disorder; each 5 parts per billion (ppb) increase in NO2, meanwhile, was linked to an increase in hospital admission rates of 0·35% (95% CI 0·03-0·66) for depression and 0·64% (0·20-1·08) for schizophrenia. No such associations were found with warm season temperature. INTERPRETATION: In the US Medicare population, short-term exposure to elevated concentrations of PM2·5 and NO2 and cold season ambient temperature were significantly associated with an increased risk of hospital admissions for psychiatric disorders. Considering the increasing burden of psychiatric disorders in the US population, these findings suggest that intervening on air pollution and ambient temperature levels through stricter environmental regulations or climate mitigation could help ease the psychiatric health-care burden. FUNDING: US National Institute of Environmental Health Sciences, US Environmental Protection Agency, and US National Institute on Aging.

Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico.

BACKGROUND: Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)-the discrepancy between chronological and epigenetic ages. METHODS: We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum's method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath's EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). RESULTS: EAA was associated with paternal education in CARDIA [GEEs: ßsome college = -1.01 years (-1.91, -0.11) and ß

Neighborhood-level disparities and subway utilization during the COVID-19 pandemic in New York City.

The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. We investigate the association between neighborhood social disadvantage and the ability to socially distance, infections, and mortality in Spring 2020. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with weighted social factors associated with infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood disadvantage is also associated with a proxy of the capacity to socially isolate, NYC subway usage data. Finally, our index is associated with COVID-19-related mortality.

Prenatal exposure to particulate air pollution and gestational age at delivery in Massachusetts neonates 2001-2015: A perspective of causal modeling and health disparities.

There is a lack of evidence on causal effects of air pollution on gestational age (GA) at delivery. METHODS: Inverse probability weighting (IPW) quantile regression was applied to derive causal marginal population-level GA reduction for GA percentiles associated with increased ambient particulate matter with diameter <2.5 µm (PM2.5) levels at maternal residential address for each trimester and the month preceding delivery using Massachusetts birth registry 2001 to 2015. Stratified analyses were conducted for neonatal sex, maternal age/race/education, and extreme ambient temperature conditions. RESULTS: For neonates at 2.5th, 10th, 25th, 50th, 75th, and 97.5th percentiles of GA at delivery, we estimated an adjusted GA reduction of 4.2 days (95% confidence interval [CI] = 3.4, 5.0), 1.9 days (1.6, 2.1), 1.2 days (1.0, 1.4), 0.82 days (0.72, 0.92), 0.74 days (0.54, 0.94), and 0.54 days (0.15, 0.93) for each 5 µg/m3 increment in third trimester average PM2.5 levels. Final gestational month average exposure yielded a similar effect with greater magnitude. Male neonates and neonates of younger (younger than 35 years) and African American mothers as well as with high/low extreme temperature exposure in third trimester were more affected. Estimates were consistently higher at lower GA percentiles, indicating preterm/early-term births being more affected. Low-exposure analyses yielded similar results, restricting to areas with PM2.5 levels under US ambient annual standard of 12 µg/m3. CONCLUSIONS: Prenatal exposure to PM2.5 in late pregnancy reduced GA at delivery among Massachusetts neonates, especially among preterm/early-term births, male neonates, and neonates of younger and African American mothers. Exposure to extremely high/low temperature amplifies the effect of PM2.5 on GA.

Can ultra short-term changes in ambient temperature trigger myocardial infarction?

BACKGROUND: Climate change is increasing global average temperatures, as well as the frequency of extreme weather events. Both low and high ambient temperatures have been associated with elevated mortality; however, little is known about the cardiovascular impacts of hourly temperature. METHODS: We assessed the association between hourly ambient temperature and risk of myocardial infarction (MI) across adult residents of New York State (NYS). We identified cases across NYS hospitals from 2000 to 2015 in the New York Department of Health Statewide Planning and Research Cooperative System dataset, using ICD codes. Hourly ambient temperature was assessed at each patient's residential ZIP code, up to 48 hours prior to MI. We employed a time-stratified case-crossover study design matching case to control periods on hour of day, day of week, month and year. RESULTS: Of the 791,695 primary MI hospital admissions, 45% were female, the mean (standard deviation; SD) age was 70 (15) years, and 49% of cases occurred among New York City residents. The observed temperature range was -29 °C to 39 °C, with a mean of 10.8 °C (10.5 °C). Temperature in the 6 h preceding the MI was positively associated with risk of MI, across the range of observed temperatures, with null or nearly null associations for earlier hours. We estimated a cumulative percent increase in hourly myocardial infarction rate of 7.9% (95% confidence interval [CI]: 5.2%, 10.6%) for an 11 °C (median) to 27 °C (95th percentile) temperature increase for lag hours 0-5. Men, Medicare-ineligible individuals (age < 65), and those experiencing their first MI were most sensitive. CONCLUSION: Our study provides evidence that increases in hourly ambient temperature can trigger myocardial infarction. Health-based definitions of extreme heat events may better capture the deleterious effects of heat by accounting for hourly temperature. Our findings can inform the design of more effective preparedness strategies for the increasingly frequent extreme heat events.

Assessing capacity to social distance and neighborhood-level health disparities during the COVID-19 pandemic.

The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. Here, we investigate the role of neighborhood social disadvantage on the ability to socially distance, infections, and mortality. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with relative weights for social factors facilitating infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood infection risk is also associated with capacity to socially isolate, as measured by NYC subway data. Finally, infection risk is associated with COVID-19-related mortality. These analyses support that differences in capacity to socially isolate is a credible pathway between disadvantage and COVID-19 disparities.

Prenatal salivary sex hormone levels and birth-weight-for-gestational age.

OBJECTIVE: To determine whether prenatal sex hormones from maternal saliva are associated with birth-weight-for-gestational age. STUDY DESIGN: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisone in 504 pregnant women in a Mexico City cohort. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth-weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education, and socioeconomic status. RESULTS: In total, 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth-weight-for-gestational age z-score (95% CI: -0.27 to -0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13-1.99). CONCLUSION: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Association between prenatal particulate air pollution exposure and telomere length in cord blood: Effect modification by fetal sex.

INTRODUCTION: In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences. METHODS: Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models. RESULTS: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys. CONCLUSIONS: Increased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.

Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.

Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants: This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures: Circulating TNF-α concentration. Main Outcomes and Measures: DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results: The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (ß [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (ß [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(ß [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (ß [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (ß [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (ß [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (ß [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). Conclusions and Relevance: We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood.

INTRODUCTION: Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5µm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood. MATERIAL AND METHODS: Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5 predictions was constructed to plot the association between exposure and OS over the length of pregnancy. RESULTS: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5 exposure during late pregnancy (35-40weeks) and lower mtDNA content in cord blood. CONCLUSIONS: Increased PM2.5 during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage.

Estimating and testing high-dimensional mediation effects in epigenetic studies.

MOTIVATION: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. RESULTS: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. AVAILABILITY AND IMPLEMENTATION: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu.

Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study.

BACKGROUND: Lead (Pb) exposure during pregnancy may increase the risk of adverse maternal, infant, or childhood health outcomes by interfering with hypothalamic-pituitary-adrenal-axis function. We examined relationships between maternal blood or bone Pb concentrations and features of diurnal cortisol profiles in 936 pregnant women from Mexico City. METHODS: From 2007-11 we recruited women from hospitals/clinics affiliated with the Mexican Social Security System. Pb was measured in blood (BPb) during the second trimester and in mothers' tibia and patella 1-month postpartum. We characterized maternal HPA-axis function using 10 timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14-35 weeks gestation). We used linear mixed models to examine the relationship between Pb biomarkers and cortisol area under the curve (AUC), awakening response (CAR), and diurnal slope. RESULTS: After adjustment for confounders, women in the highest quintile of BPb concentrations had a reduced CAR (Ratio: -13%; Confidence Interval [CI]: -24, 1, p-value for trend < 0.05) compared to women in the lowest quintile. Tibia/patella Pb concentrations were not associated with CAR, but diurnal cortisol slopes were suggestively flatter among women in the highest patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: -2, 33). BPb and bone Pb concentrations were not associated with cortisol AUC. CONCLUSIONS: Concurrent blood Pb levels were associated with cortisol awakening response in these pregnant women and this might explain adverse health outcomes associated with Pb. Further research is needed to confirm these results and determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal-axis function during pregnancy.