Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

BACKGROUND/OBJECTIVES: Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. SUBJECTS: 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. METHODS: We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. RESULTS: The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. CONCLUSIONS: Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

Power and sample size analysis for longitudinal mixed models of health in populations exposed to environmental contaminants: a tutorial.

BACKGROUND: When evaluating the impact of environmental exposures on human health, study designs often include a series of repeated measurements. The goal is to determine whether populations have different trajectories of the environmental exposure over time. Power analyses for longitudinal mixed models require multiple inputs, including clinically significant differences, standard deviations, and correlations of measurements. Further, methods for power analyses of longitudinal mixed models are complex and often challenging for the non-statistician. We discuss methods for extracting clinically relevant inputs from literature, and explain how to conduct a power analysis that appropriately accounts for longitudinal repeated measures. Finally, we provide careful recommendations for describing complex power analyses in a concise and clear manner. METHODS: For longitudinal studies of health outcomes from environmental exposures, we show how to [1] conduct a power analysis that aligns with the planned mixed model data analysis, [2] gather the inputs required for the power analysis, and [3] conduct repeated measures power analysis with a highly-cited, validated, free, point-and-click, web-based, open source software platform which was developed specifically for scientists. RESULTS: As an example, we describe the power analysis for a proposed study of repeated measures of per- and polyfluoroalkyl substances (PFAS) in human blood. We show how to align data analysis and power analysis plan to account for within-participant correlation across repeated measures. We illustrate how to perform a literature review to find inputs for the power analysis. We emphasize the need to examine the sensitivity of the power values by considering standard deviations and differences in means that are smaller and larger than the speculated, literature-based values. Finally, we provide an example power calculation and a summary checklist for describing power and sample size analysis. CONCLUSIONS: This paper provides a detailed roadmap for conducting and describing power analyses for longitudinal studies of environmental exposures. It provides a template and checklist for those seeking to write power analyses for grant applications.

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.

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age. OBJECTIVES: We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression. METHODS: Five PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture. RESULTS: In single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (-0.148 weeks per log-unit increase, 95% CI: -0.283, -0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA. CONCLUSIONS: Maternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.

Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood.

EXPOSURE TO POLY: and perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma.

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.

Unsaturated PFOS and Other PFASs in Human Serum and Drinking Water from an AFFF-Impacted Community.

Understanding how exposure to aqueous film-forming foam (AFFF)-impacted drinking water translates to bioaccumulation of per- and polyfluoroalkyl substances (PFASs) is essential to assess health risks. To investigate spatial variability of PFAS exposure in communities near an AFFF source zone, blood serum was collected in 2018 from 220 adult residents of El Paso County (Colorado), as were raw water samples from several wells. C6 and C8 perfluoroalkyl sulfonates (PFSAs) were predominant in serum and water. PFASs were most elevated in the water district nearest the source zone (median ∑PFSA of 618 ng/L in water and 33 ng/mL in serum). A novel PFAS, unsaturated perfluorooctane sulfonate, was detected in >80% of water and serum samples at low concentrations (≤1.9 ng/mL in serum). Drinking water wells nearest the source zone displayed increased prevalence of perfluoroalkyl sulfonamide precursors not detected in serum. Serum-to-water ratios were the greatest for long-chain PFASs and were elevated in the least impacted water district. Additional serum samples collected from a subset of study participants in June 2019 showed that PFAS concentrations in serum declined after exposure ceased, although declines for perfluoropentane sulfonate were minimal. Our findings demonstrate that AFFF-impacted communities are exposed to complex, spatially variable mixtures of PFASs.

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 Tobacco and Offspring Neurocognitive Development in the Healthy Start Study.

OBJECTIVE: To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. STUDY DESIGN: We followed mother-child pairs within Healthy Start through 6 years of age. Children were born at ≥37 weeks of gestation with a birth weight of ≥2500 g. Parents completed the Third Edition Ages and Stages Questionnaire (n = 246) and children completed a subset of the National Institutes of Health Toolbox Cognition Battery (n = 200). The Ages and Stages Questionnaire domains were dichotomized as fail/monitor and pass. Maternal urinary cotinine was measured at approximately 27 weeks of gestation. Separate logistic regression models estimated associations between prenatal exposure to tobacco (cotinine below vs above the limit of detection) and the Ages and Stages Questionnaire domains. Separate linear regression models estimated associations between prenatal exposure to tobacco and fully corrected T-scores for inhibitory control, cognitive flexibility, and receptive language, as assessed by the National Institutes of Health Toolbox. A priori covariates included sex, maternal age, maternal education, daily caloric intake during pregnancy, race/ethnicity, household income, maternal psychiatric disorders, and, in secondary models, postnatal exposure to tobacco. RESULTS: Compared with unexposed offspring, exposed offspring were more likely to receive a fail/monitor score for fine motor skills (OR, 3.9; 95% CI, 1.5-10.3) and decreased inhibitory control (B: -3.0; 95% CI, -6.1 to -0.7). After adjusting for postnatal exposure, only the association with fine motor skills persisted. CONCLUSIONS: Prenatal and postnatal exposures to tobacco may influence neurocognitive development, in the absence of preterm delivery or low birth weight. Increased developmental screening may be warranted for exposed children.

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.

Fetal exposure to maternal active and secondhand smoking with offspring early-life growth in the Healthy Start study.

BACKGROUND: Previous studies have modeled the association between fetal exposure to tobacco smoke and body mass index (BMI) growth trajectories, but not the timing of catch-up growth. Research on fetal exposure to maternal secondhand smoking is limited. OBJECTIVES: To explore the associations between fetal exposure to maternal active and secondhand smoking with body composition at birth and BMI growth trajectories through age 3 years. METHODS: We followed 630 mother-child pairs enrolled in the Healthy Start cohort through age 3 years. Maternal urinary cotinine was measured at ~ 27 weeks gestation. Neonatal body composition was measured using air displacement plethysmography. Child weight and length/height were abstracted from medical records. Linear regression models examined the association between cotinine categories (no exposure, secondhand smoke, active smoking) with weight, fat mass, fat-free mass, and percent fat mass at birth. A mixed-effects regression model estimated the association between cotinine categories and BMI. RESULTS: Compared to unexposed offspring, birth weight was significantly lower among offspring born to active smokers (-343-g; 95% CI: -473, -213), but not among offspring of women exposed to secondhand smoke (-47-g; 95% CI: -130, 36). There was no significant difference in the rate of BMI growth over time between offspring of active and secondhand smokers (p = 0.58). Therefore, our final model included a single growth rate parameter for the combined exposure groups of active and secondhand smokers. The rate of BMI growth for the combined exposed group was significantly more rapid (0.27 kg/m2 per year; 95% CI: 0.05, 0.69; p < 0.01) than the unexposed. CONCLUSIONS: Offspring prenatally exposed to maternal active or secondhand smoking experience rapid and similar BMI growth in the first three years of life. Given the long-term consequences of rapid weight gain in early childhood, it is important to encourage pregnant women to quit smoking and limit their exposure to secondhand smoke.

Environmental Justice in Unconventional Oil and Natural Gas Drilling and Production: A Critical Review and Research Agenda.

The drilling phase of oil and natural gas development is a growing area of environmental justice (EJ) research, particularly in the United States. Its emergence complements the longstanding EJ scholarship on later phases of the oil and gas commodity chain, such as pipeline transport, refining, and consumption. The growing scholarly attention to the EJ implications of drilling has been prompted by the surge in development of unconventional oil and gas resources in recent decades. More specifically, the oil and gas industry's adoption of horizontal drilling and hydraulic fracturing (a.k.a., "fracking" or "fracing") as methods for extracting oil and gas from a wider range of geologic formations has simultaneously heightened oil and gas production, brought extractive activities closer to more people, intensified them, and made well pad siting more flexible. Here, we provide a critical review of the novel EJ research questions that are being prompted by these on-the-ground changes in extractive techniques and patterns, propose an interdisciplinary conceptual framework for guiding EJ inquiry in this context, discuss key methodological considerations, and propose a research agenda to motivate future inquiry.

Community Noise and Air Pollution Exposure During the Development of a Multi-Well Oil and Gas Pad.

Unconventional oil and gas development (UOGD) in the United States is increasingly being conducted on multiwell pads (MWPs) and in residential areas. We measured air pollution, noise, and truck traffic during four distinct phases of UOGD: drilling, hydraulic fracturing, flowback, and production. We monitored particulate matter (PM2.5), black carbon (BC), A-weighted (dBA), and C-weighted (dBC) noise using real-time instruments on 1 and 5 min time scales, and truck traffic for 4-7 days per phase at a large 22-well pad sited in a residential area of Weld County, Colorado. Hydraulic fracturing, which requires frequent truck trips to move supplies and diesel engines to power the process, had the highest median air pollution levels of PM2.5 and BC and experienced the greatest number of heavy trucks per hour compared to other phases. Median air pollution was lowest during drilling at this MWP, possibly because an electric drill rig was used. The equivalent continuous noise level ( Leq) exceeded guidelines of 50 dBA and 65 dBC for A-weighted and C-weighted noise, respectively, during all development phases. Our data show that these multiple stressors are present around the clock at these sites, and this work provides baseline measurements on likely human exposure levels near similarly sized MWPs.

Relationships between home ventilation rates and respiratory health in the Colorado Home Energy Efficiency and Respiratory Health (CHEER) study.

BACKGROUND: As societies adopt green building practices to reduce energy expenditures and emissions that contribute to climate change, it is important to consider how such building design changes influence health. These practices typically focus on reducing air exchange rates between the building interior and the outdoor environment to minimize energy loss, the health effects of which are not well characterized. This study aims to evaluate the relationship between air exchange rates and respiratory health in a multi-ethnic population living in low-income, urban homes. METHODS: The Colorado Home Energy Efficiency and Respiratory Health (CHEER) study is a cross-sectional study that enrolled 302 people in 216 non-smoking, low-income single-family homes, duplexes and town-homes from Colorado's Northern Front Range. A blower door test was conducted and the annual average air exchange rate (AAER) was estimated for each home. Respiratory health was assessed using a structured questionnaire based on standard instruments. We estimated the association between AAER and respiratory symptoms, adjusting for relevant confounders. RESULTS: Air exchange rates in many homes were high compared to prior studies (median 0.54 air changes per hour, range 0.10, 2.17). Residents in homes with higher AAER were more likely to report chronic cough, asthma and asthma-like symptoms, including taking medication for wheeze, wheeze that limited activities and dry cough at night. Allergic symptoms were not associated with AAER in any models. The association between AAER and asthma-like symptoms was stronger for households located in areas with high potential exposure to traffic related pollutants, but this was not consistent across all health outcomes. CONCLUSIONS: While prior studies have highlighted the potential hazards of low ventilation rates in residences, this study suggests high ventilation rates in single-family homes, duplexes and town-homes in urban areas may also have negative impacts on respiratory health, possibly due to the infiltration of outdoor pollutants.

Relationships between indicators of cardiovascular disease and intensity of oil and natural gas activity in Northeastern Colorado.

BACKGROUND: Oil and natural gas (O&G) extraction emits pollutants that are associated with cardiovascular disease, the leading cause of mortality in the United States. OBJECTIVE: We evaluated associations between intensity of O&G activity and cardiovascular disease indicators. METHODS: Between October 2015 and May 2016, we conducted a cross-sectional study of 97 adults living in Northeastern Colorado. For each participant, we collected 1-3 measurements of augmentation index, systolic and diastolic blood pressure (SBP and DBP), and plasma concentrations of interleukin (IL)- 1ß, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). We modelled the intensity of O&G activity by weighting O&G well counts within 16 km of a participant's home by intensity and distance. We used linear models accounting for repeated measures within person to evaluate associations. RESULTS: Adjusted mean augmentation index differed by 6.0% (95% CI: 0.6, 11.4%) and 5.1% (95%CI: -0.1, 10.4%) between high and medium, respectively, and low exposure tertiles. The greatest mean IL-1ß, and α-TNF plasma concentrations were observed for participants in the highest exposure tertile. IL-6 and IL-8 results were consistent with a null result. For participants not taking prescription medications, the adjusted mean SBP differed by 6 and 1 mm Hg (95% CIs: 0.1, 13 mm Hg and -6, 8 mm Hg) between the high and medium, respectively, and low exposure tertiles. DBP results were similar. For participants taking prescription medications, SBP and DBP results were consistent with a null result. CONCLUSIONS: Despite limitations, our results support associations between O&G activity and augmentation index, SBP, DBP, IL-1ß, and TNF-α. Our study was not able to elucidate possible mechanisms or environmental stressors, such as air pollution and noise.

Ambient Nonmethane Hydrocarbon Levels Along Colorado's Northern Front Range: Acute and Chronic Health Risks.

Oil and gas (O&G) facilities emit air pollutants that are potentially a major health risk for nearby populations. We characterized prenatal through adult health risks for acute (1 h) and chronic (30 year) residential inhalation exposure scenarios to nonmethane hydrocarbons (NMHCs) for these populations. We used ambient air sample results to estimate and compare risks for four residential scenarios. We found that air pollutant concentrations increased with proximity to an O&G facility, as did health risks. Acute hazard indices for neurological (18), hematological (15), and developmental (15) health effects indicate that populations living within 152 m of an O&G facility could experience these health effects from inhalation exposures to benzene and alkanes. Lifetime excess cancer risks exceeded 1 in a million for all scenarios. The cancer risk estimate of 8.3 per 10 000 for populations living within 152 m of an O&G facility exceeded the United States Environmental Protection Agency's 1 in 10 000 upper threshold. These findings indicate that state and federal regulatory policies may not be protective of health for populations residing near O&G facilities. Health risk assessment results can be used for informing policies and studies aimed at reducing and understanding health effects associated with air pollutants emitted from O&G facilities.