Accuracy of self-reported distance to nearest unconventional oil and gas well in Pennsylvania, Ohio, and West Virginia residents and implications for exposure assessment.

Self-reported distances to industrial sources have been used in epidemiology as proxies for exposure to environmental hazards and indicators of awareness and perception of sources. Unconventional oil and gas development (UOG) emits pollutants and has been associated with adverse health outcomes. We compared self-reported distance to the nearest UOG well to the geographic information system-calculated distance for 303 Pennsylvania, Ohio, and West Virginia residents using Cohen's Weighted Kappa. Agreement was low (Kappa = 0.18), and self-reports by Ohioans (39% accuracy) were more accurate than West Virginians (22%) or Pennsylvanians (13%, both p < 0.05). Of the demographic characteristics studied, only educational attainment was related to reporting accuracy; residents with 12-16 years of education were more accurate (31.3% of group) than those with <12 or >16 years (both 16.7%). Understanding differences between objective and subjective measures of UOG proximity could inform studies of perceived exposures or risks and may also be relevant to adverse health effects. IMPACT: We compared objective and self-reported measures of distance to the nearest UOG well for 303 Appalachian Basin residents. We found that residents' self-reported distance to the nearest UOG well had limited agreement with the true calculated distance category. Our results can be used to inform the collection and contextualize the use of self-reported data in communities exposed to UOGD. Self-reported metrics can be used in conjunction with objective assessments and can be informative regarding how potentially exposed populations perceive environmental exposures or risks and could provide insights into awareness of distance-related policies, such as setbacks.

Multiple Dimensions of Environmental Justice and Oil and Gas Development in Pennsylvania.

Background: Community socioeconomic deprivation (CSD) may be related to higher oil and natural gas development (OGD) exposure. We tested for distributive and benefit-sharing environmental injustice in Pennsylvania's Marcellus Shale by examining (1) whether OGD and waste disposal occurred disproportionately in more deprived communities and (2) discordance between the location of land leased for OGD and where oil and gas rights owners resided. Materials and Methods: Analyses took place at the county subdivision level and considered OGD wells, waste disposal, and land lease agreement locations from 2005 to 2019. Using 2005-2009 American Community Survey data, we created a CSD index relevant to community vulnerability in suburban/rural areas. Results: In adjusted regression models accounting for spatial dependence, we observed no association between the CSD index and conventional or unconventional drilled well presence. However, a higher CSD index was linearly associated with odds of a subdivision having an OGD waste disposal site and receiving a larger volume of waste. A higher percentage of oil and gas rights owners lived in the same county subdivision as leased land when the community was least versus most deprived (66% vs. 56% in same county subdivision), suggesting that individuals in more deprived communities were less likely to financially benefit from OGD exposure. Discussion and Conclusions: We observed distributive environmental injustice with respect to well waste disposal and benefit-sharing environmental injustice related to oil and rights owner's residential locations across Pennsylvania's Marcellus Shale. These results add evidence of a disparity between exposure and benefits resulting from OGD.

Nitrate exposure from drinking water and dietary sources among Iowa farmers using private wells.

Nitrate levels are increasing in water resources across the United States and nitrate ingestion from drinking water has been associated with adverse health risks in epidemiologic studies at levels below the maximum contaminant level (MCL). In contrast, dietary nitrate ingestion has generally been associated with beneficial health effects. Few studies have characterized the contribution of both drinking water and dietary sources to nitrate exposure. The Agricultural Health Study is a prospective cohort of farmers and their spouses in Iowa and North Carolina. In 2018-2019, we assessed nitrate exposure for 47 farmers who used private wells for their drinking water and lived in 8 eastern Iowa counties where groundwater is vulnerable to nitrate contamination. Drinking water and dietary intakes were estimated using the National Cancer Institute Automated Self-Administered 24-Hour Dietary Assessment tool. We measured nitrate in tap water and estimated dietary nitrate from a database of food concentrations. Urinary nitrate was measured in first morning void samples in 2018-19 and in archived samples from 2010 to 2017 (minimum time between samples: 2 years; median: 7 years). We used linear regression to evaluate urinary nitrate concentrations in relation to total nitrate, and drinking water and dietary intakes separately. Overall, dietary nitrate contributed the most to total intake (median: 97 %; interquartile range [IQR]: 57-99 %). Among 15 participants (32 %) whose drinking water nitrate concentrations were at/above the U.S. Environmental Protection Agency MCL (10 mg/L NO3-N), median intake from water was 44 % (IQR: 26-72 %). Total nitrate intake was the strongest predictor of urinary nitrate concentrations (R2 = 0.53). Drinking water explained a similar proportion of the variation in nitrate excretion (R2 = 0.52) as diet (R2 = 0.47). Our findings demonstrate the importance of both dietary and drinking water intakes as determinants of nitrate excretion.

US drinking water quality: exposure risk profiles for seven legacy and emerging contaminants.

BACKGROUND: Advances in drinking water infrastructure and treatment throughout the 20th and early 21st century dramatically improved water reliability and quality in the United States (US) and other parts of the world. However, numerous chemical contaminants from a range of anthropogenic and natural sources continue to pose chronic health concerns, even in countries with established drinking water regulations, such as the US. OBJECTIVE/METHODS: In this review, we summarize exposure risk profiles and health effects for seven legacy and emerging drinking water contaminants or contaminant groups: arsenic, disinfection by-products, fracking-related substances, lead, nitrate, per- and polyfluorinated alkyl substances (PFAS) and uranium. We begin with an overview of US public water systems, and US and global drinking water regulation. We end with a summary of cross-cutting challenges that burden US drinking water systems: aging and deteriorated water infrastructure, vulnerabilities for children in school and childcare facilities, climate change, disparities in access to safe and reliable drinking water, uneven enforcement of drinking water standards, inadequate health assessments, large numbers of chemicals within a class, a preponderance of small water systems, and issues facing US Indigenous communities. RESULTS: Research and data on US drinking water contamination show that exposure profiles, health risks, and water quality reliability issues vary widely across populations, geographically and by contaminant. Factors include water source, local and regional features, aging water infrastructure, industrial or commercial activities, and social determinants. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general problems, ascertaining the state of drinking water resources, and developing mitigation strategies. IMPACT STATEMENT: Drinking water contamination is widespread, even in the US. Exposure risk profiles vary by contaminant. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general public health problems, ascertaining the state of drinking water resources, and developing mitigation strategies.

Predictors of early life residential mobility in urban and rural Pennsylvania children with acute lymphoblastic leukemia and implications for environmental exposure assessment.

BACKGROUND: Residential mobility can introduce exposure misclassification in pediatric epidemiology studies using birth address only. OBJECTIVE: We examined whether residential mobility varies by sociodemographic factors and urbanicity/rurality among children with cancer. METHODS: Our study included 400 children born in Pennsylvania during 2002-2015 and diagnosed with leukemia at ages 2-7 years. Addresses were obtained from state registries at birth and diagnosis. We considered three aspects of mobility between birth and diagnosis: whether a child moved, whether a mover changed census tract, and distance moved. We evaluated predictors of these aspects in urban- and rural-born children using chi-square, t-tests, and regression analyses. RESULTS: Overall, 58% of children moved between birth and diagnosis; suburban/rural-born children were more likely to move than urban-born children (67% versus 57%). The mean distance moved was 16.7 km in suburban/rural-born and 14.8 km in urban-born movers. In urban-born children, moving between birth and diagnosis was associated with race, education, participation in the Nutrition Program for Women, Infants and Children (WIC), and census tract-level income (all χ2 p < 0.01). Urban-born movers tended to be born in a census tract with a higher Social Vulnerability Index than non-movers (t-test p < 0.01). No factors were statistically significantly associated with any of the residential mobility metrics in suburban/rural-born children, although the sample size was small. IMPACT STATEMENT: In this study of a vulnerable population of children with cancer, we found that rural-born children were more likely to move than urban-born children, however, the frequency of movers changing census tracts was equivalent. Mobility in urban-born children, but not rural-born, was associated with several social factors, although the sample size for rural-born children was small. Mobility could be an important source of misclassification depending on the spatial heterogeneity and resolution of the exposure data and whether the social factors are related to exposures or health outcomes. Our results highlight the importance of considering differences in mobility between urban and rural populations in spatial research.

Investigation of Sources of Fluorinated Compounds in Private Water Supplies in an Oil and Gas-Producing Region of Northern West Virginia.

Per- and polyfluoroalkyl substances (PFASs) are a class of toxic organic compounds that have been widely used in consumer applications and industrial activities, including oil and gas production. We measured PFAS concentrations in 45 private wells and 8 surface water sources in the oil and gas-producing Doddridge, Marshall, Ritchie, Tyler, and Wetzel Counties of northern West Virginia and investigated relationships between potential PFAS sources and drinking water receptors. All surface water samples and 60% of the water wells sampled contained quantifiable levels of at least one targeted PFAS compound, and four wells (8%) had concentrations above the proposed maximum contaminant level (MCL) for perfluorooctanoic acid (PFOA). Individual concentrations of PFOA and perfluorobutanesulfonic acid exceeded those measured in finished public water supplies. Total targeted PFAS concentrations ranged from nondetect to 36.8 ng/L, with surface water concentrations averaging 4-fold greater than groundwater. Semiquantitative, nontargeted analysis showed concentrations of emergent PFAS that were potentially higher than targeted PFAS. Results from a multivariate latent variable hierarchical Bayesian model were combined with insights from analyses of groundwater chemistry, topographic characteristics, and proximity to potential PFAS point sources to elucidate predictors of PFAS concentrations in private wells. Model results reveal (i) an increased vulnerability to contamination in upland recharge zones, (ii) geochemical controls on PFAS transport likely driven by adsorption, and (iii) possible influence from nearby point sources.

Conventional Fossil Fuel Extraction, Associated Biogeochemical Processes, and Topography Influence Methane Groundwater Concentrations in Appalachia.

The production of fossil fuels, including oil, gas, and coal, retains a dominant share in US energy production and serves as a major anthropogenic source of methane, a greenhouse gas with a high warming potential. In addition to directly emitting methane into the air, fossil fuel production can release methane into groundwater, and that methane may eventually reach the atmosphere. In this study, we collected 311 water samples from an unconventional oil and gas (UOG) production region in Pennsylvania and an oil and gas (O&G) and coal production region across Ohio and West Virginia. Methane concentration was negatively correlated to distance to the nearest O&G well in the second region, but such a correlation was shown to be driven by topography as a confounding variable. Furthermore, sulfate concentration was negatively correlated with methane concentration and with distance to coal mining in the second region, and these correlations were robust even when considering topography. We hypothesized that coal mining enriched sulfate in groundwater, which in turn inhibited methanogenesis and enhanced microbial methane oxidation. Thus, this study highlights the complex interplay of multiple factors in shaping groundwater methane concentrations, including biogeochemical conversion, topography, and conventional fossil extraction.

Per- and polyfluoroalkyl substances (PFAS) and thyroid hormone measurements in dried blood spots and neonatal characteristics: a pilot study.

BACKGROUND: Pediatric thyroid diseases have been increasing in recent years. Environmental risk factors such as exposures to chemical contaminants may play a role but are largely unexplored. Archived neonatal dried blood spots (DBS) offer an innovative approach to investigate environmental exposures and effects. OBJECTIVE: In this pilot study, we applied a new method for quantifying per- and polyfluoroalkyl substances (PFAS) to 18 archived DBS from babies born in California from 1985-2018 and acquired thyroid hormone measurements from newborn screening tests. Leveraging these novel data, we evaluated (1) changes in the concentrations of eight PFAS over time and (2) the relationship between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics to inform future research. METHODS: PFAS concentrations in DBS were measured using ultra-high-performance liquid chromatography-mass spectrometry. Summary statistics and non-parametric Wilcoxon rank-sum and Kruskal-Wallis tests were used to evaluate temporal changes in PFAS concentrations and relationships between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics. RESULTS: The concentration and detection frequencies of several PFAS (PFOA, PFOS, and PFOSA) declined over the assessment period. We observed that the timing of specimen collection in hours after birth was related to thyroid hormone but not PFAS concentrations, and that thyroid hormones were related to some PFAS concentrations (PFOA and PFOS). IMPACT STATEMENT: This pilot study examines the relationship between concentrations of eight per- and polyfluoroalkyl substances (PFAS), thyroid hormone levels, and neonatal characteristics in newborn dried blood spots (DBS) collected over a period of 33 years. To our knowledge, 6 of the 22 PFAS we attempted to measure have not been quantified previously in neonatal DBS, and this is the first study to examine both PFAS and thyroid hormone concentrations using DBS. This research demonstrates the feasibility of using newborn DBS for quantifying PFAS exposures in population-based studies, highlights methodological considerations in the use of thyroid hormone data for future studies using newborn DBS, and indicates potential relationships between PFAS concentrations and thyroid hormones for follow-up in future research.

Per- and polyfluoroalkyl substances and sleep health in U.S. adults, NHANES 2005-2014.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that induce oxidative inflammatory responses and disrupt the endocrine and central nervous systems, all of which can influence sleep. OBJECTIVE: To investigate the association between PFAS exposure and sleep health measures in U.S. adults. METHODS: We analyzed serum concentration data of four PFAS [perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] reported for 8913 adults in NHANES 2005-2014. Sleep outcomes, including trouble sleeping, having a diagnosis of sleep disorder, and recent daily sleep duration classified as insufficient or excessive sleep (<6 or >9 h/day) were examined. Weighted logistic regression was used to estimate the association between the sleep outcomes and each PFAS modeled continuously (log2) or in exposure tertiles. We applied quantile g-computation to estimate the effect of the four PFAS as a mixture on the sleep outcomes. We conducted a quantitative bias analysis to assess the potential influence of self-selection and uncontrolled confounding. RESULTS: We observed some inverse associations between serum PFAS and trouble sleeping or sleep disorder, which were more consistent for PFOS (e.g., per log2-PFOS (ng/ml) and trouble sleeping OR = 0.93, 95%CI: 0.89, 0.98; sleep disorder OR = 0.89, 95%CI: 0.83, 0.95). Per quartile increase of the PFAS mixture was inversely associated with trouble sleeping and sleep disorder. No consistent associations were found for sleep duration across analyses. Our bias analysis suggests that the finding on sleep disorder could be explained by a moderate level of self-selection and negative confounding effects. CONCLUSIONS: We found no evidence to suggest exposure to four legacy PFAS worsened self-reported sleep health among U.S. adults. While some inverse associations between specific PFAS and sleep disorder were observed, self-selection and uncontrolled confounding biases may play a role in these findings.

Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study.

BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score >1, false discovery rate-corrected q-value<0.1). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125.

High Ambient Temperature in Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia.

Background: High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, the incidence is increasing, and in the United States it disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood ALL. Methods: We used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed <14 years and 50 times as many controls matched by sex, race/ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. Association between ambient temperature and ALL was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy) and constructed an alternatively matched dataset for exposure contrast by seasonality. Findings: Our study included 6,258 ALL cases and 307,579 controls. The peak association between ambient temperature and risk of ALL was observed in gestational week 8, where a 5 °C increase was associated with an odds ratio of 1.09 (95% confidence interval 1.04-1.14) and 1.05 (95% confidence interval 1.00-1.11) among Latino and non-Latino White children, respectively. The sensitivity analyses supported this. Interpretation: Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood ALL. Further replication and investigation of mechanistic pathways may inform mitigation strategies.

Social Vulnerability and Groundwater Vulnerability to Contamination From Unconventional Hydrocarbon Extraction in the Appalachian Basin.

Unconventional oil and gas (UOG) development, made possible by horizontal drilling and high-volume hydraulic fracturing, has been fraught with controversy since the industry's rapid expansion in the early 2000's. Concerns about environmental contamination and public health risks persist in many rural communities that depend on groundwater resources for drinking and other daily needs. Spatial disparities in UOG risks can pose distributive environmental injustice if such risks are disproportionately borne by marginalized communities. In this paper, we analyzed groundwater vulnerability to contamination from UOG as a physically based measure of risk in conjunction with census tract level sociodemographic characteristics describing social vulnerability in the northern Appalachian Basin. We found significant associations between elevated groundwater vulnerability and lower population density, consistent with UOG development occurring in less densely populated rural areas. We also found associations between elevated groundwater vulnerability and lower income, higher proportions of elderly populations, and higher proportion of mobile homes, suggesting a disproportionate risk burden on these socially vulnerable groups. We did not find a statistically significant association between elevated groundwater vulnerability and populations of racial/ethnic minorities in our study region. Household surveys provided empirical support for a relationship between sociodemographic characteristics and capacity to assess and mitigate exposures to potentially contaminated water. Further research is needed to probe if the observed disparities translate to differences in chemical exposure and adverse health outcomes.

It's electric! An environmental equity perspective on the lifecycle of our energy sources.

Energy policy decisions are driven primarily by economic and reliability considerations, with limited consideration given to public health, environmental justice, and climate change. Moreover, epidemiologic studies relevant for public policy typically focus on immediate public health implications of activities related to energy procurement and generation, considering less so health equity or the longer-term health consequences of climate change attributable to an energy source. A more integrated, collective consideration of these three domains can provide more robust guidance to policymakers, communities, and individuals. Here, we illustrate how these domains can be evaluated with respect to natural gas as an energy source. Our process began with a detailed overview of all relevant steps in the process of extracting, producing, and consuming natural gas. We synthesized existing epidemiologic and complementary evidence of how these processes impact public health, environmental justice, and climate change. We conclude that, in certain domains, natural gas looks beneficial (e.g., economically for some), but when considered more expansively, through the life cycle of natural gas and joint lenses of public health, environmental justice, and climate change, natural gas is rendered an undesirable energy source in the United States. A holistic climate health equity framework can inform how we value and deploy different energy sources in the service of public health.

Residential proximity to unconventional oil and gas development and birth defects in Ohio.

BACKGROUND: Chemicals used or emitted by unconventional oil and gas development (UOGD) include reproductive/developmental toxicants. Associations between UOGD and certain birth defects were reported in a few studies, with none conducted in Ohio, which experienced a thirty-fold increase in natural gas production between 2010 and 2020. METHODS: We conducted a registry-based cohort study of 965,236 live births in Ohio from 2010 to 2017. Birth defects were identified in 4653 individuals using state birth records and a state surveillance system. We assigned UOGD exposure based on maternal residential proximity at birth to active UOG wells and a metric specific to the drinking-water exposure pathway that identified UOG wells hydrologically connected to a residence ("upgradient UOG wells"). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for all structural birth defects combined and specific birth defect types using binary exposure metrics (presence/absence of any UOG well and presence/absence of an upgradient UOG well within 10 km), adjusting for confounders. Additionally, we conducted analyses stratified by urbanicity, infant sex, and social vulnerability. RESULTS: The odds of any structural defect were 1.13 times higher in children born to mothers living within 10 km of UOGD than those born to unexposed mothers (95%CI: 0.98-1.30). Odds were elevated for neural tube defects (OR: 1.57, 95%CI: 1.12-2.19), limb reduction defects (OR: 1.99, 95%CI: 1.18-3.35), and spina bifida (OR 1.93; 95%CI 1.25-2.98). Hypospadias (males only) was inversely related to UOGD exposure (OR: 0.62, 95%CI: 0.43-0.91). Odds of any structural defect were greater in magnitude but less precise in analyses using the hydrological-specific metric (OR: 1.30; 95%CI: 0.85-1.90), in areas with high social vulnerability (OR: 1.27, 95%CI: 0.99-1.60), and among female offspring (OR: 1.28, 95%CI: 1.06-1.53). CONCLUSIONS: Our results suggest a positive association between UOGD and certain birth defects, and findings for neural tube defects corroborate results from prior studies.

Health risks of heavy metals in food and their economic burden in Armenia.

Mining leads to excessive heavy metal contamination of agricultural products in Armenia and can adversely impact human health. We quantify the concentrations of toxic heavy metals (lead, nickel, cadmium, and mercury) in food sampled from local markets of the capital city, Yerevan. We combine these measured concentrations with data from a diet survey of 1,195 people. The results provide an estimate of people's heavy metal intake in a typical day. The study finds that only dietary exposure to lead raises consumer safety concerns. More than 50 % of the population have daily intakes of lead that exceed the benchmark dose level (BMDL10) of 0.63 µg/kg b.w./day established by European Food Safety Authority. Moreover, risk assessment results indicate that approximately 96 % of the population has dietary exposure values for lead that exceed the threshold level, with animal products as the primary source. The lead exposure observed in sampled population has the potential to increase blood pressure on average by 0.54 mmHg, lower IQ levels by 1.2 point, and reduce lifetime earnings by $5000. The study reveals a strong need to determine the specific pathways by which lead enters the food supply, to mitigate the excess exposures, and to reduce the potential or severity of the resulting adverse health impacts.

Urinary phenol concentrations and fecundability and early pregnancy loss.

STUDY QUESTION: Are urinary phenol concentrations of methylparaben, propylparaben, butylparaben, triclosan, benzophenone-3, 2,4-dichlorophenol or 2,5-dichlorophenol associated with fecundability and early pregnancy loss? SUMMARY ANSWER: 2,5-dichlorophenol concentrations were associated with an increased odds of early pregnancy loss, and higher concentrations of butylparaben and triclosan were associated with an increase in fecundability. WHAT IS KNOWN ALREADY: Phenols are chemicals with endocrine-disrupting potential found in everyday products. Despite plausible mechanisms of phenol reproductive toxicity, there are inconsistent results across few epidemiologic studies examining phenol exposure and reproductive function in non-fertility treatment populations. STUDY DESIGN, SIZE, DURATION: Specimens and data were from the North Carolina Early Pregnancy Study prospective cohort of 221 women attempting to conceive naturally from 1982 to 1986. This analysis includes data from 221 participants across 706 menstrual cycles, with 135 live births, 15 clinical miscarriages and 48 early pregnancy losses (before 42 days after the last menstrual period). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants collected daily first-morning urine specimens. For each menstrual cycle, aliquots from three daily specimens across the cycle were pooled within individuals and analyzed for phenol concentrations. To assess sample repeatability, we calculated intraclass correlation coefficients (ICCs) for each phenol. We evaluated associations between phenol concentrations from pooled samples and time to pregnancy using discrete-time logistic regression and generalized estimating equations (GEE), and early pregnancy loss using multivariable logistic regression and GEE. MAIN RESULTS AND THE ROLE OF CHANCE: ICCs for within-person variability across menstrual cycles in pooled phenol concentrations ranged from 0.42 to 0.75. There was an increased odds of early pregnancy loss with 2,5-dichlorophenol concentrations although the CIs were wide (5th vs 1st quintile odds ratio (OR): 4.79; 95% CI: 1.06, 21.59). There was an increased per-cycle odds of conception at higher concentrations of butylparaben (OR: 1.62; 95% CI: 1.08, 2.44) and triclosan (OR: 1.49; 95% CI: 0.99, 2.26) compared to non-detectable concentrations. No associations were observed between these endpoints and concentrations of other phenols examined. LIMITATIONS, REASONS FOR CAUTION: Limitations include the absence of phenol measurements for male partners and a limited sample size, especially for the outcome of early pregnancy loss, which reduced our power to detect associations. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to use repeated pooled measures to summarize phenol exposure and the first to investigate associations with fecundability and early pregnancy loss. Within-person phenol concentration variability underscores the importance of collecting repeated samples for future studies. Exposure misclassification could contribute to differences between the findings of this study and those of other studies, all of which used one urine sample to assess phenol exposure. This study also contributes to the limited literature probing potential associations between environmental exposures and early pregnancy loss, which is a challenging outcome to study as it typically occurs before a pregnancy is clinically recognized. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health (award number F31ES030594), the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (project numbers ES103333 and ES103086) and a doctoral fellowship at the Yale School of Public Health. The authors declare they have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Assessing community-level exposure to social vulnerability and isolation: spatial patterning and urban-rural differences.

BACKGROUND: Environmental health disparity research involves the use of metrics to assess exposure to community-level vulnerabilities or inequities. While numerous vulnerability indices have been developed, there is no agreement on standardization or appropriate use, they have largely been applied in urban areas, and their interpretation and utility likely vary across different geographies. OBJECTIVE: We evaluated the spatial distribution, variability, and relationships among different metrics of social vulnerability and isolation across urban and rural settings to inform interpretation and selection of metrics for environmental disparity research. METHODS: For all census tracts in North Carolina, we conducted a principal components analysis using 23 socioeconomic/demographic variables from the 2010 United States Census and American Community Survey. We calculated or obtained the neighborhood deprivation index (NDI), residential racial isolation index (RI), educational isolation index (EI), Gini coefficient, and social vulnerability index (SVI). Statistical analyses included Moran's I for spatial clustering, t-tests for urban-rural differences, Pearson correlation coefficients, and changes in ranking of tracts across metrics. RESULTS: Social vulnerability metrics exhibited clear spatial patterning (Moran's I ≥ 0.30, p < 0.01). Greater educational isolation and more intense neighborhood deprivation was observed in rural areas and greater racial isolation in urban areas. Single-domain metrics were not highly correlated with each other (rho ≤ 0.36), while composite metrics (i.e., NDI, SVI, principal components analysis) were highly correlated (rho > 0.80). Composite metrics were more highly correlated with the racial isolation metric in urban (rho: 0.54-0.64) versus rural tracts (rho: 0.36-0.48). Census tract rankings changed considerably based on which metric was being applied. SIGNIFICANCE: High correlations between composite metrics within urban and rural tracts suggests they could be used interchangeably; single domain metrics cannot. Composite metrics capture different facets of vulnerabilities in urban and rural settings, and these complexities should be examined by researchers applying metrics to areas of diverse urban and rural forms.

Hemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study.

Dried blood spot (DBS) metabolomics has numerous applications in newborn health screening, exposomics, and biomonitoring of environmental chemicals in pregnant women and the elderly. However, accurate metabolite quantification is hindered by several challenges: notably the "hematocrit effect" and unknown blood-spotting volumes. Different techniques have been employed to overcome these issues but there is no consensus on the optimal normalization method for DBS metabolomics, and in some cases no normalization is used. We compared five normalization methods (hemoglobin (Hb), specific gravity (SG), protein, spot weight, potassium (K+)) to unnormalized data, and assessed sex-related differences in the DBS metabolome in 21 adults (group 1, n = 10 males, n = 11 females). The performance of each normalization method was evaluated using multiple criteria: (a) reduction of intragroup variation (pooled median absolute deviation, pooled estimate of variance, pooled coefficient of variation, NMDS and principal component analysis), (b) effect on differential metabolic analysis (dendrogram, heatmap, p-value distribution), and (c) influence on classification accuracy (partial least squares discriminant analysis, sparse partial least squares discriminant analysis error rates, receiver operating curve, random forest out of bag error rate). Our results revealed that Hb normalization outperformed all the other methods based on the three criteria and 13 different parameters; the performance of Hb was further demonstrated in an independent group of DBS from 18 neonates (group 2, n = 9 males, n = 9 females). Furthermore, we showed that SG and Hb are correlated in adults (rs = 0.86, p < 0.001), and validated this relationship in an independent group of 18 neonates and infants (group 3) (rs = 0.84, p < 0.001). Using the equation, SG = -0.4814Hb2 + 2.44Hb + 0.005, SG can be used as a surrogate for normalization by Hb. This is the first comparative study to concurrently evaluate multiple normalization methods for DBS metabolomics which will serve as a robust methodological platform for future environmental epidemiological studies.