Independent and joint effects of neighborhood-level environmental and socioeconomic exposures on body mass index in early childhood: The environmental influences on child health outcomes (ECHO) cohort.

Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables.

Neighborhood Walkability, Historical Redlining, and Childhood Obesity in Denver, Colorado.

Childhood obesity is a precursor to future health complications. In adults, neighborhood walkability is inversely associated with obesity prevalence. Recently, it has been shown that current urban walkability has been influenced by historical discriminatory neighborhood disinvestment. However, the relationship between this systemic racism and obesity has not been extensively studied. The objective of this study was to evaluate the association of neighborhood walkability and redlining, a historical practice of denying home loans to communities of color, with childhood obesity. We evaluated neighborhood walkability and walkable destinations for 250 participants of the Healthy Start cohort, based in the Denver metropolitan region. Eligible participants attended an examination between ages 4 and 8. Walkable destinations and redlining geolocations were determined based on residential addresses, and a weighting system for destination types was developed. Sidewalks and trails in Denver were included in the network analyst tool in ArcMap to calculate the precise walkable environment for each child. We implemented linear regression models to estimate associations between neighborhood characteristics and child body mass index (BMI) z-scores and fat mass percent. There was a significant association between child BMI and redlining (ß: 1.36, 95% CI: 0.106, 2.620). We did not find an association between walkability measures and childhood obesity outcomes. We propose that cities such as Denver pursue built environment policies, such as inclusionary zoning and direct investments in neighborhoods that have been historically neglected, to reduce the childhood health impacts of segregated poverty, and suggest further studies on the influences that redlining and urban built environment factors have on childhood obesity.

Early-life exposure to residential black carbon and childhood cardiometabolic health.

BACKGROUND: Early life exposure to air pollution, such as particulate matter ≤2.5 µm (PM2.5), may be associated with obesity and adverse cardiometabolic health outcomes in childhood. However, the toxicity of PM2.5 varies according to its chemical composition. Black carbon (BC) is a constituent of PM2.5, but few studies have examined its impact on childhood cardiometabolic health. Therefore, we examined relationships between prenatal and early childhood exposure to BC and markers of adiposity and cardiometabolic health in early childhood. METHODS: This study included 578 mother-child pairs enrolled in the Healthy Start study (2009-2014) living in the Denver-metro area. Using a spatiotemporal prediction model, we assessed average residential black carbon levels during pregnancy and in the year prior to the early childhood follow-up visit at approximately 5 years old. We estimated associations between prenatal and early childhood BC and indicators of adiposity and cardiometabolic biomarkers in early childhood (mean 4.8 years; range, 4.0, 8.3), using linear regression. RESULTS: We found higher early childhood BC was associated with higher percent fat mass, fat mass index, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR), and lower leptin and waist circumference at approximately 5 years old, after adjusting for covariates. For example, per interquartile range (IQR) increase in early childhood BC (IQR, 0.49 µg/m3) there was 3.32% higher fat mass (95% CI; 2.05, 4.49). Generally, we did not find consistent evidence of associations between prenatal BC and cardiometabolic health outcomes in early childhood, except for an inverse association between prenatal BC and adiponectin, an adipocyte-secreted hormone typically inversely associated with adiposity. CONCLUSIONS: Higher early childhood, but not in utero, ambient concentrations of black carbon, a component of air pollution, were associated with greater adiposity and altered insulin homeostasis at approximately 5 years old. Future studies should examine whether these changes persist later in life.

The COVID-19-wildfire smoke paradox: Reduced risk of all-cause mortality due to wildfire smoke in Colorado during the first year of the COVID-19 pandemic.

BACKGROUND: In 2020, the American West faced two competing challenges: the COVID-19 pandemic and the worst wildfire season on record. Several studies have investigated the impact of wildfire smoke (WFS) on COVID-19 morbidity and mortality, but little is known about how these two public health challenges impact mortality risk for other causes. OBJECTIVES: Using a time-series design, we evaluated how daily risk of mortality due to WFS exposure differed for periods before and during the COVID-19 pandemic. METHODS: Our study included daily data for 11 counties in the Front Range region of Colorado (2010-2020). We assessed WFS exposure using data from the National Oceanic and Atmospheric Administration and used mortality counts from the Colorado Department of Public Health and Environment. We estimated the interaction between WFS and the pandemic (an indicator variable) on mortality risk using generalized additive models adjusted for year, day of week, fine particulate matter, ozone, temperature, and a smoothed term for day of year. RESULTS: WFS impacted the study area on 10% of county-days. We observed a positive association between the presence of WFS and all-cause mortality risk (incidence rate ratio (IRR) = 1.03, 95%CI: 1.01-1.04 for same-day exposures) during the period before the pandemic; however, WFS exposure during the pandemic resulted in decreased risk of all-cause mortality (IRR = 0.90, 95%CI: 0.87-0.93 for same-day exposures). DISCUSSION: We hypothesize that mitigation efforts during the first year of the pandemic, e.g., mask mandates, along with high ambient WFS levels encouraged health behaviors that reduced exposure to WFS and reduced risk of all-cause mortality. Our results suggest a need to examine how associations between WFS and mortality are impacted by pandemic-related factors and that there may be lessons from the pandemic that could be translated into health-protective policies during future wildfire events.

Prenatal exposure to ambient air pollution and traffic and indicators of adiposity in early childhood: the Healthy Start study.

BACKGROUND: Prenatal exposure to ambient air pollution and traffic have been related to a lower birth weight and may be associated with greater adiposity in childhood. We aimed to examine associations of maternal exposure to ambient air pollution and traffic during pregnancy with indicators of adiposity in early childhood. METHODS: We included 738 participants of the Colorado-based Healthy Start study whose height, weight, waist circumference and/or fat mass were measured at age 4-6 years. We estimated residential exposure to ambient concentrations of fine particulate matter (PM2.5) and ozone (O3) averaged by trimester and throughout pregnancy via inverse distance-weighted interpolation of central site monitoring data. We assessed the distance to the nearest major roadway and traffic density in multiple buffers surrounding the participants' homes. Associations of prenatal exposure to air pollution and traffic with overweight, waist circumference, percent fat mass and fat mass index (FMI) were assessed by logistic and linear regression. RESULTS: Associations of exposure to PM2.5 and O3 at the residential address during pregnancy with percent fat mass and FMI at age 4-6 years were inconsistent across trimesters. For example, second trimester PM2.5 was associated with a higher percent fat mass (adjusted difference 0.70% [95% CI 0.05, 1.35%] per interquartile range (IQR; 1.3 µg/m3) increase), while third trimester PM2.5 was associated with a lower percent fat mass (adjusted difference -1.17% [95% CI -1.84, -0.50%] per IQR (1.3 µg/m3) increase). Residential proximity to a highway during pregnancy was associated with higher odds of being overweight at age 4-6 years. We observed no associations of prenatal exposure to PM2.5 and O3 with overweight and waist circumference. CONCLUSIONS: We found limited evidence of associations of prenatal exposure to ambient PM2.5 and O3 with indicators of adiposity at age 4-6 years. Suggestive relationships between residential proximity to a highway during pregnancy and greater adiposity merit further investigation.

Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study.

BACKGROUND: Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth. METHODS: Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM2.5) and ozone (O3), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM2.5 and O3 in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O3 exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood. RESULTS: We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O3 on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant. CONCLUSIONS: Differentially methylated regions in cord blood were identified in association with maternal exposure to PM2.5 and O3. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O3 exposure and 5-month infant adiposity.

Using non-parametric Bayes shrinkage to assess relationships between multiple environmental and social stressors and neonatal size and body composition in the Healthy Start cohort.

BACKGROUND: Both environmental and social factors have been linked to birth weight and adiposity at birth, but few studies consider the effects of exposure mixtures. Our objective was to identify which components of a mixture of neighborhood-level environmental and social exposures were driving associations with birth weight and adiposity at birth in the Healthy Start cohort. METHODS: Exposures were assessed at the census tract level and included air pollution, built environment characteristics, and socioeconomic status. Prenatal exposures were assigned based on address at enrollment. Birth weight was measured at delivery and adiposity was measured using air displacement plethysmography within three days. We used non-parametric Bayes shrinkage (NPB) to identify exposures that were associated with our outcomes of interest. NPB models were compared to single-predictor linear regression. We also included generalized additive models (GAM) to assess nonlinear relationships. All regression models were adjusted for individual-level covariates, including maternal age, pre-pregnancy BMI, and smoking. RESULTS: Results from NPB models showed most exposures were negatively associated with birth weight, though credible intervals were wide and generally contained zero. However, the NPB model identified an interaction between ozone and temperature on birth weight, and the GAM suggested potential non-linear relationships. For associations between ozone or temperature with birth weight, we observed effect modification by maternal race/ethnicity, where effects were stronger for mothers who identified as a race or ethnicity other than non-Hispanic White. No associations with adiposity at birth were observed. CONCLUSIONS: NPB identified prenatal exposures to ozone and temperature as predictors of birth weight, and mothers who identify as a race or ethnicity other than non-Hispanic White might be disproportionately impacted. However, NPB models may have limited applicability when non-linear effects are present. Future work should consider a two-stage approach where NPB is used to reduce dimensionality and alternative approaches examine non-linear effects.

Relationships between social climate and indoor environmental quality and frequently reported health symptoms among teachers and staff in a suburban school district.

Public school teachers represent one of the largest occupational groups in the United States and are vulnerable to job stress and burnout. School social and physical environments may be adversely impacting the health of teachers and other staff, though few studies have explored these relationships. We partnered with a suburban school district in Colorado to assess the association between school environmental quality, social climate, and staff member health. We modeled the number of self-reported frequent health symptoms (experienced at least once a week) using generalized linear models. School-level predictors of interest included: overall social climate scores (unitless), building operations report card (ORC) scores (unitless), and indoor air quality (IAQ) scores (unitless). In total, we had data from 134 staff members from 11 schools in the district. A majority (62%) of our participants were teachers, who reported a greater number of frequent (i.e., at least once a week) health symptoms (mean = 3.2 symptoms experienced at least once per week) compared to staff in other roles (mean = 2.3 symptoms per week). We found that a one standard-deviation (10.5) increase in the overall social climate score was associated with a 0.77-fold (95% CI: 0.60-0.99) change in the number of frequent health symptoms reported. However, this association was attenuated among teachers compared to other staff members. Our results suggested effect modification by social climate on the relationship between IAQ and health, albeit with some uncertainty. For participants with a school climate score below the mean, a one standard-deviation (10.5) increase in IAQ score was associated with a 0.49-fold (95% CI: 0.35-0.70) change in the number of frequently reported symptoms. Overall, our study suggests school climate may be associated with self-reported health symptoms, but that the benefits of improved school climates may not be as strong for teachers compared to other staff. Future work should assess perceived climate at the individual level to assess how staff roles impact how school environments are associated with health outcomes.

A Spatiotemporal Prediction Model for Black Carbon in the Denver Metropolitan Area, 2009-2020.

Studies on health effects of air pollution from local sources require exposure assessments that capture spatial and temporal trends. To facilitate intraurban studies in Denver, Colorado, we developed a spatiotemporal prediction model for black carbon (BC). To inform our model, we collected more than 700 weekly BC samples using personal air samplers from 2018 to 2020. The model incorporated spatial and spatiotemporal predictors and smoothed time trends to generate point-level weekly predictions of BC concentrations for the years 2009-2020. Our results indicate that our model reliably predicted weekly BC concentrations across the region during the year in which we collected data. We achieved a 10-fold cross-validation R2 of 0.83 and a root-mean-square error of 0.15 µg/m3 for weekly BC concentrations predicted at our sampling locations. Predicted concentrations displayed expected temporal trends, with the highest concentrations predicted during winter months. Thus, our prediction model improves on typical land use regression models that generally only capture spatial gradients. However, our model is limited by a lack of long-term BC monitoring data for full validation of historical predictions. BC predictions from the weekly spatiotemporal model will be used in traffic-related air pollution exposure-disease associations more precisely than previous models for the region have allowed.

Exposure to ambient air pollution during pregnancy and inflammatory biomarkers in maternal and umbilical cord blood: The Healthy Start study.

BACKGROUND: Air pollution exposure during pregnancy has been associated with adverse pregnancy and birth outcomes. Inflammation has been proposed as a potential link. We estimated associations between air pollution exposure during pregnancy and inflammatory biomarkers in maternal and cord blood. We evaluated whether maternal inflammation was associated with infant outcomes. METHODS: Among 515 mother-infant dyads in the Healthy Start study (2009-2014), trimester-long, 7- and 30-day average concentrations of particulate matter ≤2.5 µm (PM2.5) and ozone (O3) during pregnancy were estimated, using inverse-distance-weighted interpolation. Inflammatory biomarkers were measured in maternal blood in mid-pregnancy (C-reactive protein [CRP], Interleukin [IL]-6, and tumor necrosis factor-α [TNFα]) and in cord blood at delivery (CRP, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], and TNFα). We used linear regression to estimate associations between pollutants and inflammatory biomarkers and maternal inflammatory biomarkers and infant weight and body composition. RESULTS: There were positive associations between PM2.5 during certain exposure periods and maternal IL-6 and TNFα. There were negative associations between recent O3 and maternal CRP, IL-6, and TNFα and positive associations between trimester-long O3 exposure and maternal inflammatory biomarkers, though some 95% confidence intervals included the null. Patterns were inconsistent for associations between PM2.5 and O3 and cord blood inflammatory biomarkers. No consistent associations between maternal inflammatory biomarkers and infant outcomes were identified. CONCLUSIONS: Air pollution exposure during pregnancy may impact maternal inflammation. Further investigations should examine the health consequences for women and infants of elevated inflammatory biomarkers associated with air pollution exposure during pregnancy.

Prenatal exposure to traffic and ambient air pollution and infant weight and adiposity: The Healthy Start study.

BACKGROUND: Prenatal exposures to ambient air pollution and traffic have been associated with adverse birth outcomes, and may also lead to an increased risk of obesity. Obesity risk may be reflected in changes in body composition in infancy. OBJECTIVE: To estimate associations between prenatal ambient air pollution and traffic exposure, and infant weight and adiposity in a Colorado-based prospective cohort study. METHODS: Participants were 1125 mother-infant pairs with term births. Birth weight was recorded from medical records and body composition measures (fat mass, fat-free mass, and adiposity [percent fat mass]) were evaluated via air displacement plethysmography at birth (n = 951) and at ~5 months (n = 574). Maternal residential address was used to calculate distance to nearest roadway, traffic density, and ambient concentrations of fine particulate matter (PM2.5) and ozone (O3) via inverse-distance weighted interpolation of stationary monitoring data, averaged by trimester and throughout pregnancy. Adjusted linear regression models estimated associations between exposures and infant weight and body composition. RESULTS: Participants were urban residents and diverse in race/ethnicity and socioeconomic status. Average ambient air pollutant concentrations were generally low; the median, interquartile range (IQR), and range of third trimester concentrations were 7.3 µg/m3 (IQR: 1.3, range: 3.3-12.7) for PM2.5 and 46.3 ppb (IQR: 18.4, range: 21.7-63.2) for 8-h maximum O3. Overall there were few associations between traffic and air pollution exposures and infant outcomes. Third trimester O3 was associated with greater adiposity at follow-up (2.2% per IQR, 95% CI 0.1, 4.3), and with greater rates of change in fat mass (1.8 g/day, 95% CI 0.5, 3.2) and adiposity (2.1%/100 days, 95% CI 0.4, 3.7) from birth to follow-up. CONCLUSIONS: We found limited evidence of an association between prenatal traffic and ambient air pollution exposure and infant body composition. Suggestive associations between prenatal ozone exposure and early postnatal changes in body composition merit further investigation.

Effectiveness of Using Enhanced Filters in Schools and Homes to Reduce Indoor Exposures to PM2.5 from Outdoor Sources and Subsequent Health Benefits for Children with Asthma.

Filters can reduce indoor concentrations of particulate matter (PM2.5), but their benefits have not been well-characterized. This study investigates exposure, health, and cost impacts of high efficiency filters in homes and schools, focusing on the asthma-related outcomes. Reductions in indoor exposures to PM2.5 from outdoor sources with enhanced filters (e.g., MERV 12) are estimated using probabilistic indoor air quality models, and avoided health impacts are quantified using health impact assessment. These methods are applied using data from Detroit, Michigan, an urban region with elevated asthma rates. Replacing inefficient filters with enhanced filters in schools would reduce the PM2.5-attributable asthma burden by 13% annually, with higher benefits for more efficient filters. Marginal costs average $63 per classroom or $32 per child with asthma per year. In homes, using efficient furnace filters or air cleaners yields 11 to 16% reductions in the asthma burden with an annualized marginal costs of $151-494 per household. Additional benefits include reductions in health risk for adults and lower exposures to other contaminants such as PM from indoor sources. On the basis of the included health outcomes, efficient filters in schools in particular is a potentially cost-efficient way to reduce the asthma-related health burden for children.

Semi-automated scoring of triple-probe FISH in human sperm using confocal microscopy.

Structural and numerical sperm chromosomal aberrations result from abnormal meiosis and are directly linked to infertility. Any live births that arise from aneuploid conceptuses can result in syndromes such as Kleinfelter, Turners, XYY and Edwards. Multi-probe fluorescence in situ hybridization (FISH) is commonly used to study sperm aneuploidy, however manual FISH scoring in sperm samples is labor-intensive and introduces errors. Automated scoring methods are continuously evolving. One challenging aspect for optimizing automated sperm FISH scoring has been the overlap in excitation and emission of the fluorescent probes used to enumerate the chromosomes of interest. Our objective was to demonstrate the feasibility of combining confocal microscopy and spectral imaging with high-throughput methods for accurately measuring sperm aneuploidy. Our approach used confocal microscopy to analyze numerical chromosomal abnormalities in human sperm using enhanced slide preparation and rigorous semi-automated scoring methods. FISH for chromosomes X, Y, and 18 was conducted to determine sex chromosome disomy in sperm nuclei. Application of online spectral linear unmixing was used for effective separation of four fluorochromes while decreasing data acquisition time. Semi-automated image processing, segmentation, classification, and scoring were performed on 10 slides using custom image processing and analysis software and results were compared with manual methods. No significant differences in disomy frequencies were seen between the semi automated and manual methods. Samples treated with pepsin were observed to have reduced background autofluorescence and more uniform distribution of cells. These results demonstrate that semi-automated methods using spectral imaging on a confocal platform are a feasible approach for analyzing numerical chromosomal aberrations in sperm, and are comparable to manual methods. © 2017 International Society for Advancement of Cytometry.

Dialkyl phosphate urinary metabolites and chromosomal abnormalities in human sperm.

BACKGROUND: The past decade has seen numerous human health studies seeking to characterize the impacts of environmental exposures, such as organophosphate (OP) insecticides, on male reproduction. Despite an extensive literature on OP toxicology, many hormone-mediated effects on the testes are not well understood. OBJECTIVES: This study investigated environmental exposures to OPs and their association with the frequency of sperm chromosomal abnormalities (i.e., disomy) among adult men. METHODS: Men (n=159) from a study assessing the impact of environmental exposures on male reproductive health were included in this investigation. Multi-probe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX18, YY18, XY18 and total disomy in sperm nuclei. Urine was analyzed using gas chromatography coupled with mass spectrometry for concentrations of dialkyl phosphate (DAP) metabolites of OPs [dimethylphosphate (DMP); dimethylthiophosphate (DMTP); dimethyldithiophosphate (DMDTP); diethylphosphate (DEP); diethylthiophosphate (DETP); and diethyldithiophosphate (DEDTP)]. Poisson regression was used to model the association between OP exposures and disomy measures. Incidence rate ratios (IRRs) were calculated for each disomy type by exposure quartiles for most metabolites, controlling for age, race, BMI, smoking, specific gravity, total sperm concentration, motility, and morphology. RESULTS: A significant positive trend was seen for increasing IRRs by exposure quartiles of DMTP, DMDTP, DEP and DETP in XX18, YY18, XY18 and total disomy. A significant inverse association was observed between DMP and total disomy. Findings for total sum of DAP metabolites concealed individual associations as those results differed from the patterns observed for each individual metabolite. Dose-response relationships appeared nonmonotonic, with most of the increase in disomy rates occurring between the second and third exposure quartiles and without additional increases between the third and fourth exposure quartiles. CONCLUSIONS: This is the first epidemiologic study of this size to examine the relationship between environmental OP exposures and human sperm disomy outcomes. Our findings suggest that increased disomy rates were associated with specific DAP metabolites, suggesting that the impacts of OPs on testis function need further characterization in epidemiologic studies.

Prenatal black carbon exposure and DNA methylation in umbilical cord blood.

BACKGROUND/OBJECTIVES: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts. METHODS: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood. RESULTS: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84). CONCLUSIONS: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.

Environmental exposure to pyrethroids and sperm sex chromosome disomy: a cross-sectional study.

BACKGROUND: The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome disomy in adult men. METHODS: A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates. RESULTS: Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 disomy rates 1.28 times higher (95% CI: 1.15, 1.42) whereas a reduced rate was seen for XY18 and total disomy (IRR = 0.82; 95% CI: 0.77, 0.87; IRR = 0.93; 95% CI: 0.87-0.97), and no association was seen for XX18 and 1818. CONCLUSIONS: Our findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent. This is the first study to examine these relationships, and replication of our findings is needed before the association between pyrethroid metabolites and aneuploidy can be fully defined.

Beyond the Imodium, a One Health Discussion on Diarrhea and the Impact of Climate Change.

Our ability to tackle the looming human, animal, and global ecosystem health threats arising from the issues of climate change and extreme weather events will require effective and creative cross-disciplinary collaboration. There is a growing national and international interest in equipping the next generation of clinicians and health scientists for success in facing these important challenges by providing interprofessional training opportunities. This paper describes how we assembled an interdisciplinary team of experts to design and deliver a case-based discussion on a cross-species illness outbreak in animals and humans using a One Health framework. The small group, case-based approach highlighted the impact of climate change-driven extreme weather events on human and animal health using a diarrhea outbreak associated with a contaminated community water supply precipitated by extreme flooding. Post-activity survey data indicated that this team-taught learning activity successfully engaged a cross-disciplinary cohort of medical, veterinary, and public health students in the issues of environmental public health threats and helped them understand the importance of an integrative, cross-functional, team-based approach for solving complex problems. The data from this study is being used to plan similar interprofessional, One Health learning activities across the health sciences curriculum in our institution.

Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Early-life exposure to tobacco and childhood adiposity: Identifying windows of susceptibility.

BACKGROUND: Early-life exposure to tobacco is associated with obesity, but the most susceptible developmental periods are unknown. OBJECTIVE: To explore windows of susceptibility in a cohort of 568 mother-child pairs. METHODS: We measured seven measures of tobacco exposure (five self-reported and two biomarkers) spanning from pre-conception to age 5 years. Mothers self-reported active smoking (pre-conception, 17 weeks, and delivery) and household smokers (5 and 18 months postnatally). Cotinine was measured in maternal urine (27 weeks) and child urine (5 years). Adiposity (fat mass percentage) was measured at birth and 5 years via air displacement plethysmography. Using a multiple informant approach, we tested whether adiposity (5 years) and changes in adiposity (from birth to 5 years) differed by the seven measures of tobacco exposure. RESULTS: The associations may depend on timing. For example, only pre-conception (ß = 3.1%; 95% CI: 1.0-5.1) and late gestation (ß = 4.0%; 95% CI: 0.4-7.6) exposures influenced adiposity accretion from birth to 5 years (p for interaction = 0.01). Early infancy exposure was also associated with 1.7% higher adiposity at 5 years (95% CI: 0.1-3.2). Mid-pregnancy and early childhood exposures did not influence adiposity. CONCLUSIONS: Pre-conception, late gestation, and early infancy exposures to tobacco may have the greatest impact on childhood adiposity.

Ambient air pollution during pregnancy and cardiometabolic biomarkers in cord blood.

Prenatal air pollution exposure has been associated with adverse childhood cardiometabolic outcomes. It is unknown whether evidence of metabolic disruption associated with air pollution is identifiable at birth. We examined exposure to prenatal ambient air pollution and cord blood cardiometabolic biomarkers among 812 mother-infant pairs in the Healthy Start study. Methods: Using inverse-distance-weighted interpolation of ambient concentrations obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full-pregnancy, and the 7 and 30 days prior to delivery. Associations of air pollution with the following cord blood biomarkers were estimated via multivariable linear regression: glucose, insulin, glucose/insulin ratio (GIR), leptin, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, free fatty acids, and triglycerides. Results: In this Denver-based cohort, PM2.5 concentrations were lower than in many US urban areas, but O3 concentrations regularly exceeded federal air quality standards. Higher O3 concentrations during pregnancy were consistently associated with higher insulin and lower GIR in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 parts per billion [ppb]) was associated with 0.13 log-µIU/ml (95% confidence interval [CI] = 0.04, 0.22) higher cord blood insulin, after adjusting for PM2.5 and other confounders. We found positive, but generally nonsignificant, associations between PM2.5 and leptin and isolated associations between pollutants during certain exposure periods and lipids. Conclusions: In this cohort with moderately high O3 exposure, prenatal concentrations of O3 were positively associated with cord blood insulin. Future studies should examine the implications for offspring long-term health.