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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.

Concerns over unconventional oil and gas (UOG) development persist, especially in rural communities that rely on shallow groundwater for drinking and other domestic purposes. Given the continued expansion of the industry, regional (vs local scale) models are needed to characterize groundwater contamination risks faced by the increasing proportion of the population residing in areas that accommodate UOG extraction. In this paper, we evaluate groundwater vulnerability to contamination from surface spills and shallow subsurface leakage of UOG wells within a 104,000 km

BackgroundHigh 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.MethodsWe used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed FindingsOur 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.InterpretationOur 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.

Purpose of Review Epidemiologic studies have observed elevated health risks in populations living near unconventional oil and gas development (UOGD). In this narrative review, we discuss strengths and limitations of UOG exposure assessment approaches used in or available for epidemiologic studies, emphasizing studies of children’s health outcomes. Recent Findings Exposure assessment challenges include (1) numerous potential stressors with distinct spatiotemporal patterns, (2) critical exposure windows that cover long periods and occur in the past, and (3) limited existing monitoring data coupled with the resource-intensiveness of collecting new exposure measurements to capture spatiotemporal variation. All epidemiologic studies used proximity-based models for exposure assessment as opposed to surveys, biomonitoring, or environmental measurements. Nearly all studies used aggregate (rather than pathway-specific) models, which are useful surrogates for the complex mix of potential hazards. Summary Simple and less-specific exposure assessment approaches have benefits in terms of scalability, interpretability, and relevance to specific policy initiatives such as set-back distances. More detailed and specific models and metrics, including dispersion methods and stressor-specific models, could reduce exposure misclassification, illuminate underlying exposure pathways, and inform emission control and exposure mitigation strategies. While less practical in a large population, collection of multi-media environmental and biological exposure measurements would be feasible in cohort subsets. Such assessments are well-suited to provide insights into the presence and magnitude of exposures to UOG-related stressors in relation to spatial surrogates and to better elucidate the plausibility of observed effects in both children and adults.

With growing evidence of widespread health and environmental impacts from oil and gas activity, localities and states are beginning to develop protective measures. Interdisciplinary approaches that integrate across human, wildlife, domesticated animal, and land health are likely to provide more just and comprehensive solutions than would be possible with siloed approaches. However, this is not common practice, and there is little guidance on how to apply such a strategy. In the present article, we summarize the state of knowledge on the impacts of terrestrial unconventional oil and gas development from the fields of ecology and public health. We then discuss synergies and trade-offs regarding impacts and mitigation strategies emerging from these two literatures. Finally, we provide recommendations for research and practice to fill knowledge gaps and better inform integrated decision-making to achieve multiple benefits and minimize impacts on human, wildlife, domesticated animals, and land health from energy development.

Health studies report associations between metrics of residential proximity to unconventional oil and gas (UOG) development and adverse health endpoints. We investigated whether exposure through household groundwater is captured by existing metrics and a newly developed metric incorporating groundwater flow paths. We compared metrics with detection frequencies/concentrations of 64 organic and inorganic UOG-related chemicals/groups in residential groundwater from 255 homes (Pennsylvania n = 94 and Ohio n = 161). Twenty-seven chemicals were detected in ≥20% of water samples at concentrations generally below U.S. Environmental Protection Agency standards. In Pennsylvania, two organic chemicals/groups had reduced odds of detection with increasing distance to the nearest well: 1,2-dichloroethene and benzene (Odds Ratio [OR]: 0.46, 95% confidence interval [CI]: 0.23–0.93) and m- and p-xylene (OR: 0.28, 95% CI: 0.10–0.80); results were consistent across metrics. In Ohio, the odds of detecting toluene increased with increasing distance to the nearest well (OR: 1.48, 95% CI: 1.12–1.95), also consistent across metrics. Correlations between inorganic chemicals and metrics were limited (all |ρ| ≤ 0.28). Limited associations between metrics and chemicals may indicate that UOG-related water contamination occurs rarely/episodically, more complex metrics may be needed to capture drinking water exposure, and/or spatial metrics in health studies may better reflect exposure to other stressors.

Horizontal drilling with hydraulic fracturing (HDHF) relies on the use of anthropogenic organic chemicals in proximity to residential areas, raising concern for groundwater contamination. Here, we extensively characterized organic contaminants in 94 domestic groundwater sites in Northeastern Pennsylvania after ten years of activity in the region. All analyzed volatile and semi-volatile compounds were below recommended United States Environmental Protection Agency maximum contaminant levels, and integrated concentrations across two volatility ranges, gasoline range organic compounds (GRO) and diesel range organic compounds (DRO), were low (0.13 ± 0.06 to 2.2 ± 0.7 ppb and 5.2-101.6 ppb, respectively). Following dozens of correlation analyses with distance-to-well metrics and inter-chemical indicator correlations, no statistically significant correlations were found except: (1) GRO levels were higher within 2 km of violations and (2) correlation between DRO and a few inorganic species (

Detecting sharp differences, or boundaries, in areal data can uncover important biological, physical and/or social differences between spatial regions. We introduce a new discrete areal data kernel function for use in the kernel stick-breaking process framework that is shown to yield improved (i) detection of spatial boundaries, (ii) estimation of regression parameters and (iii) model fit through a simulation study and comparison with existing approaches. We use the model to analyse county-level hydraulic fracturing Class II injection well counts in Ohio, where interesting boundary patterns may exist due to the close connection between hydraulic fracturing and shale rock formations. Class II injection wells are used for disposing hydraulic fracturing liquid waste and may pose an environmental risk for surrounding communities. Counties located on the Devonian shale with increased poverty, less income equality, smaller proportion of the population that is white, and increased population density are found to contain more wells, with the relationship reversed for counties off the shale. Results suggest that the new method provides improved model fit and is robust to the exclusion of an important spatially varying covariate, while also detecting boundaries surrounding different shale rock formations. The method is implemented in the R package KSBound.

Conflicting evidence exists as to whether or not unconventional oil and gas (UOG) development has enhanced methane transport into groundwater aquifers over the past 15 years. In this study, recent groundwater samples were collected from 90 domestic wells and 4 springs in Northeastern Pennsylvania located above the Marcellus Shale after more than a decade of UOG development. No statistically significant correlations were observed between the groundwater methane level and various UOG geospatial metrics, including proximity to UOG wells and well violations, as well as the number of UOG wells and violations within particular radii. The δ

Unconventional oil and gas development (UOGD) releases chemicals that have been linked to cancer and childhood leukemia. Studies of UOGD exposure and childhood leukemia are extremely limited.The objective of this study was to evaluate potential associations between residential proximity to UOGD and risk of acute lymphoblastic leukemia (ALL), the most common form of childhood leukemia, in a large regional sample using UOGD-specific metrics, including a novel metric to represent the water pathway.We conducted a registry-based case-control study of 405 children ages 2-7 y diagnosed with ALL in Pennsylvania between 2009-2017, and 2,080 controls matched on birth year. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between residential proximity to UOGD (including a new water pathway-specific proximity metric) and ALL in two exposure windows: a primary window (3 months preconception to 1 y prior to diagnosis/reference date) and a perinatal window (preconception to birth).Children with at least one UOG well withinOur study including a novel UOGD metric found UOGD to be a risk factor for childhood ALL. This work adds to mounting evidence of UOGD's impacts on children's health, providing additional support for limiting UOGD near residences. https://doi.org/10.1289/EHP11092.

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 (r

Objectives Farmers may be exposed to glucans (a cell component of molds) through a variety of tasks. The magnitude of exposure depends on each farmer’s activities and their duration. We developed a task-specific algorithm to estimate glucan exposure that combines measurements of (1→3)-β-D-glucan with questionnaire responses from farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. Methods To develop the algorithm, we first derived task-based geometric means (GMs) of glucan exposure for farming tasks using inhalable personal air sampling data from a prior air monitoring study in a subset of 32 BEEA farmers. Next, these task-specific GMs were multiplied by subject-reported activity frequencies for three time windows (the past 30 days, past 7 days, and past 1 day) to obtain subject-, task-, and time window-specific glucan scores. These were summed together to obtain a total glucan score for each subject and time window. We examined the within- and between-task correlation in glucan scores for different time frames. Additionally, we assessed the algorithm for the ‘past 1 day’ time window using full-shift concentrations from the 32 farmers who participated in air monitoring the day prior to an interview using multilevel statistical models to compare the measured glucan concentration with algorithm glucan scores. Results We focused on the five highest exposed tasks: poultry confinement (300 ng/m3), swine confinement (300 ng/m3), clean grain bins (200 ng/m3), grind feed (100 ng/m3), and stored seed or grain (50 ng/m3); the remaining tasks were Conclusions This study provides insight into the variability and key sources of glucan exposure in a US farming population. It also provides a framework for better glucan exposure assessment in epidemiologic studies and is a crucial starting point for evaluating health risks associated with glucans in future epidemiologic evaluations of this population.

In the United States, concentrations of criteria air pollutants have declined in recent decades. Questions remain regarding whether improvements in air quality are equitably distributed across subpopulations. We assessed spatial variability and temporal trends in concentrations of particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) and ozone (O3) across North Carolina from 2002–2016, and associations with community characteristics. Estimated daily PM2.5 and O3 concentrations at 2010 Census tracts were obtained from the Fused Air Quality Surface Using Downscaling archive and averaged to create tract-level annual PM2.5 and O3 estimates. We calculated tract-level measures of: racial isolation of non-Hispanic Black individuals, educational isolation of non–college educated individuals, the neighborhood deprivation index (NDI), and percentage of the population in urban areas. We fitted hierarchical Bayesian space-time models to estimate baseline concentrations of and time trends in PM2.5 and O3 for each tract, accounting for spatial between-tract correlation. Concentrations of PM2.5 and O3 declined by 6.4 μg/m3 and 13.5 ppb, respectively. Tracts with lower educational isolation and higher urbanicity had higher PM2.5 and more pronounced declines in PM2.5. Racial isolation was associated with higher PM2.5 but not with the rate of decline in PM2.5. Despite declines in pollutant concentrations, over time, disparities in exposure increased for racially and educationally isolated communities.

Few studies have evaluated the validity of self-report of work activities because of challenges in obtaining objective measures. In this study, farmers’ recall of the previous day’s agricultural activities was compared to activities observed by field staff during air monitoring. Recall was assessed in 32 farmers from the Biomarkers of Exposure and Effect in Agriculture Study, a subset of a prospective cohort study. The farmers participated in 56 visits that comprised air monitoring the day before an interview. The answers for 14 agricultural activities were compared to activities observed by field staff during air monitoring (median duration 380 minutes, range 129–486). For each task, evaluated as yes/no, overall agreement, sensitivity, specificity, and kappa were calculated. Median prevalence of the 14 activities was 8% from observation and 13% from participants (range: 2–54%). Agreement was generally good to perfect, with a median overall agreement of 95% (range: 89–100%), median sensitivity of 84% (50–100%), median specificity of 95% (88–100%), and median kappa of 0.65 (0.31–1.0). Reasons for disagreement included activities occurring when the field staff was not present (i.e., milking cows), unclear timing notes that made it difficult to determine whether the activity occurred the day of and/or day before the interview, definition issues (i.e., participant included hauling in the definition of harvesting), and difficulty in observing details of an activity (i.e., whether hay was moldy). This study provides support for accurate participant recall the day after activities.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied.OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age.METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median=8 gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child's sex were performed.RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling OR=2.02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures.DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. https://doi.org/10.1289/EHP9478.