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Background: The causes of autism spectrum disorders (ASD) remain largely unknown and widely debated; however, evidence increasingly points to the importance of environmental exposures. A growing number of studies use geographic variability in ASD prevalence or exposure patterns to investigate the association between environmental factors and ASD. However, differences in the geographic distribution of established risk and predictive factors for ASD, such as maternal education or age, can interfere with investigations of ASD etiology. We evaluated geographic variability in the prevalence of ASD in central North Carolina and the impact of spatial confounding by known risk and predictive factors. Methods. Children meeting a standardized case definition for ASD at 8 years of age were identified through records-based surveillance for 8 counties biennially from 2002 to 2008 (n=532). Vital records were used to identify the underlying cohort (15% random sample of children born in the same years as children with an ASD, n=11,034), and to obtain birth addresses. We used generalized additive models (GAMs) to estimate the prevalence of ASD across the region by smoothing latitude and longitude. GAMs, unlike methods used in previous spatial analyses of ASD, allow for extensive adjustment of individual-level risk factors (e.g. maternal age and education) when evaluating spatial variability of disease prevalence. Results: Unadjusted maps revealed geographic variation in surveillance-recognized ASD. Children born in certain regions of the study area were up to 1.27 times as likely to be recognized as having ASD compared to children born in the study area as a whole (prevalence ratio (PR) range across the study area 0.57-1.27; global P=0.003). However, geographic gradients of ASD prevalence were attenuated after adjusting for spatial confounders (adjusted PR range 0.72-1.12 across the study area; global P=0.052). Conclusions: In these data, spatial variation of ASD in central NC can be explained largely by factors impacting diagnosis, such as maternal education, emphasizing the importance of adjusting for differences in the geographic distribution of known individual-level predictors in spatial analyses of ASD. These results underscore the critical importance of accounting for such factors in studies of environmental exposures that vary across regions. © 2012 Hoffman et al.; licensee BioMed Central Ltd.

Background: Children living in communities with lower socioeconomic status and higher minority populations are often disproportionately exposed to particulate matter (PM) compared to children living in other communities., Objective: We assessed whether adding HEPA filter air cleaners to classrooms with existing HVAC systems reduces indoor air pollution exposure., Methods: From July 2022 to June 2023, using a block randomized crossover trial of 17 Los Angeles Unified School District elementary schools, classroom PM concentrations were monitored and compared for 99 classrooms with HEPA filter air cleaners and 87 classrooms with non-HEPA filter air cleaners., Results: In HEPA classrooms, average school-year PM 2.5 was 39.9% lower (0.581 µg/m³; p < 0.001) and infiltration of outdoor PM 2.5 into classrooms was 13.8-82.4% lower than non-HEPA classrooms, depending on the school., Impact: Few studies have examined HEPA filtration in a classroom environment, and this is one of the first studies since the COVID-19 pandemic to assess PM exposure in the classroom. Using a well powered block randomized crossover trial, we showed that adding portable HEPA air cleaners to classrooms that already had HVAC systems with MERV 13 air filters resulted in lower measurable PM concentrations and less infiltration of outdoor PM 2.5 compared to control classrooms with non-HEPA filters. This demonstrates that further improvements in classroom air quality, especially in environmentally burdened communities, can be achieved with additional filtration., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The Institutional Review Board at University of California, Irvine, and the Data Privacy, Analysis, & Reporting Branch and the Strategic Data and Evaluation Branch at LAUSD approved this study., (© 2025. The Author(s).)

Background: Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015., Methods: Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls. A pharmacokinetic model was used to predict average steady-state maternal serum concentrations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) from contaminated drinking water. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) per doubling of background exposure were calculated for cancers with at least 90 cases., Results: Predicted PFOS and PFOA maternal serum concentrations ranged from background (5 ng/ml PFOS and 2 ng/ml PFOA) to 22.89 ng/ml and 6.66 ng/ml, respectively. There were suggestive associations between PFOS and nonastrocytoma gliomas (n = 268; AOR = 1.26; 95% CI: 0.99, 1.60), acute myeloid leukemia (n = 500; AOR = 1.14; 95% CI: 0.94, 1.39), Wilms tumors (n = 556, AOR = 1.15; 95% CI: 0.96, 1.38), and noncentral system embryonal tumors (n = 2,880; AOR = 1.07; 95% CI: 0.98, 1.17), and between PFOA and non-Hodgkin lymphoma (n = 384; AOR = 1.19; 95% CI: 0.95, 1.49). Among children of Mexico-born mothers, there was increased risk of Wilms tumor (n = 101; AOR PFOS = 1.52; 95% CI: 1.06, 2.18; AOR PFOA = 1.59, 95% CI: 1.12, 2.24) and noncentral system embryonal tumors (n = 557; AOR PFOS = 1.24, 95% CI: 1.03, 1.50; AOR PFOA = 1.19, 95% CI: 0.98, 1.45)., Conclusion: Results suggest associations between predicted prenatal maternal PFAS serum concentrations and some childhood cancers. Future analyses are warranted., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dirofilaria immitis infection is routinely detected in dogs during veterinary care in tropical and subtropical regions worldwide. Parasitological tests for the detection of this infection are routinely performed only in areas with a high prevalence. Baixada Fluminense, a region in Rio de Janeiro, was considered heartworm-free until local veterinarians began to receive blood exams results indicating the presence of microfilariae (MF). A laboratory database was hence used to collect data from 2017 to 2020 to understand the extent of spread of the parasite in this area. The results of complete blood count analysis and MF or heartworm antigen detection tests conducted on canine samples sent from veterinary clinics in Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti municipalities) were included. In total, the results of 16,314 hematological tests were considered. The overall prevalence of D. immitis was 3.4% (554/16,314), considering that only one test result was obtained per animal on the same day. This study is highly relevant because it indicates the spreading geographic distribution of the worms, heightens awareness among local health professionals and the general population, and encourages compliance with prophylactic measures to prevent further spread of parasite., Competing Interests: NL is a consultant for Boehringer Ingelheim and Zoetis in Brazil. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Andrade Vieira, da Silva, Paulino, do Amaral Fernandes, Labarthe, Gazêta and de Moraes Neto.)

Unmatched spatially stratified random sampling (SSRS) of non-cases selects geographically balanced controls by dividing the study area into spatial strata and randomly selecting controls from all non-cases within each stratum. The performance of SSRS control selection was evaluated in a case study spatial analysis of preterm birth in Massachusetts. In a simulation study, we fit generalized additive models using controls selected by SSRS or simple random sample (SRS) designs. We compared mean squared error (MSE), bias, relative efficiency (RE), and statistically significant map results to the model results with all non-cases. SSRS designs had lower average MSE (0.0042-0.0044) and higher RE (77-80%) compared to SRS designs (MSE: 0.0072-0.0073; RE across designs: 71%). SSRS map results were more consistent across simulations, reliably identifying statistically significant areas. SSRS designs improved efficiency by selecting controls that are geographically distributed, particularly from low population density areas, and may be more appropriate for spatial analyses., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous studies have suggested that traffic-related air pollution is associated with adverse fertility outcomes, such as reduced fecundability and subfertility. The purpose of this research is to investigate if PM 2.5 exposure prior to conception or traffic-related exposures (traffic density and distance to nearest major roadway) at birth address is associated with fertility-assisted births. We obtained all live and still births from the Massachusetts state birth registry with an estimated conception date between January 2002 through December 2008. All births requiring fertility drugs or assisted reproductive technology were identified as cases. We randomly selected 2000 infants conceived each year to serve as a common control group. PM 2.5 exposure was assessed using 4 km spatial satellite remote sensing, meteorological and land use spatiotemporal models at geocoded birth addresses for the year prior to conception. The mean PM 2.5 level was 9.81 µ g m -3 (standard deviation = 1.70 µ g m -3 ), with a maximum of 14.27 µ g m -3 . We calculated crude and adjusted fertility treatment odds ratios (ORs) and 95% confidence intervals (CI) per interquartile range of 1.72 µ g m -3 increase in PM 2.5 exposure. Our final analyses included 10 748 fertility-assisted births and 12 225 controls. After adjusting for parental age, marital status, race, maternal education, insurance status, parity, and year of birth, average PM 2.5 exposure during the year prior to conception was weakly associated with fertility treatment (OR: 1.01; 95% CI: 0.97, 1.05). Fertility-assisted births were inversely associated with traffic density (highest quartile compared to lowest quartile, OR: 0.92; 95% CI: 0.83, 1.02) and positively associated with distance from major roadway (OR per 100 m: 1.01; 95% CI: 1.00, 1.02) in adjusted analyses. We did not find strong evidence to support an adverse relationship between traffic-related air pollution exposure and fertility-assisted births., Competing Interests: All authors have indicated they have no financial relationships relevant to this article to disclose., (© 2023 The Author(s). Published by IOP Publishing Ltd.)

Background: The detection of cancer in its early latent stages can improve patients' chances of recovery and thereby reduce the overall burden of the disease. Our objectives were to investigate factors (geographic accessibility and deprivation level) affecting mammography screening participation variation and to determine how much geographic variation in participation rates can be explained by spillover effects between adjacent areas, while controlling for covariates., Methods: Mammography screening participation rates between 2015 and 2016 were calculated by census blocks (CB), for women aged 50-74 years, residing in Lyon metropolitan area. Global spatial autocorrelation tests were applied to identify the geographic variation of participation. Spatial regression models were used to incorporate spatial structure to estimate associations between mammography participation rate and the combined effect (geographic accessibility and deprivation level) adjusting for modes of travel and social cohesion., Results: The mammography participation rate was found to have a statistically significant and positive spatial correlation. The participation rate of one CB was significantly and positively associated with the participation rates of neighbouring CB. The participation was 53.2% in residential and rural areas and 46.6% in urban areas, p < 0.001. Using Spatial Lag models, whereas the population living in most deprived CBs have statistically significantly lower mammography participation rates than lower deprived ones, significant interaction demonstrates that the relation differs according to the degree of urbanization., Conclusions: This study makes an important methodological contribution in measuring geographical access and understanding better the combined effect of deprivation and the degree of urbanization on mammography participation and other contextual factors that affect the decision of using mammography screening services -which is a critical component of healthcare planning and equity., (© 2022. The Author(s).)

Background: Research suggests that geographic location may affect ovarian cancer (OC) outcomes. Insurance status often remains an important predictor of outcomes. The Affordable Care Act was enacted in 2010 to expand access to affordable health insurance. Our objective was to examine spatiotemporal trends in OC treatment nonadherence and disease-specific mortality in California (USA) among women diagnosed with OC., Methods: Newly diagnosed epithelial OC cases between 1996 and 2017 were identified from the California Cancer Registry. Spatiotemporal trends in adherence to treatment guidelines were examined using generalized additive models and OC-specific mortality using Cox proportional hazards additive models. Prediction grids covering California were used to display the odds ratios (ORs) and hazard ratios of location using the median value for the study area as the referent value. Seven overlapping 5-year periods and 2 larger ones (pre- and post-2013) were assessed. Analyses were stratified according to stage (early vs advanced) and used P = .05 to determine statistical significance., Results: Statistically significant spatial patterns in treatment nonadherence were observed for every time period examined (P < .001). Odds of treatment nonadherence associated with geographic location were highest among women with early-stage OC in southern Los Angeles County during 2014-2017 (OR max = 3.89, confidence interval = 1.04 to 7.61). For women with advanced-stage OC, residing in northern California was generally associated with lower odds ratios, whereas southern California was associated with higher odds ratios, with higher odds in the latter time period (OR range = 0.53-1.84 in 1996-2012 vs 0.49-2.37 in 2013-2017). Geographic location was not a statistically significant predictor of mortality., Conclusions: Residential location was statistically significantly associated with treatment received in California, with spatial patterns varying over time but not OC-specific mortality. Changes in insurance status over time were accompanied by shifts in population demographics and increased travel distances to receive care., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: To understand the complexity of high-risk care for pregnant women in the health care network., Method: Qualitative study with theoretical framework of Edgar Morin's Complex Thought and Grounded Theory methodology, Strauss's version. Data collection by theoretical sampling, including twelve health professionals and seven women users of the care network in a municipality in the south of Brazil from July to October 2018. Analysis by open and axial coding and selective integration., Results: The phenomenon "Caring for high-risk pregnant women in the health care network", comprises four categories: Noticing autonomous decision making; Promoting care; Developing multiprofessional work; and Accessing the health care network., Conclusion: Every high-risk pregnant woman should be seen as a singular and multidimensional being with comprehensive and continuous care, considering the complexity of local, regional, and global reality.

Objective: Cannabis and tobacco retailers are believed to cluster in areas with more racial/ethnic minorities, which could account for the disproportionate use of blunts in Black and Hispanic communities. The current study examined the spatial relationship between cannabis and licensed tobacco retailers in Los Angeles County, California, and assessed whether various neighborhood and business factors influenced the spatial patterning., Method: Generalized additive models were used to test the association between the location of cannabis retailers ( N = 429) and their accessibility potential (AP) to tobacco retailers ( N = 8,033). The covariates included cannabis licensure status, median household income, population density, percentages of racial/ ethnic minorities and young adults (18-34), unemployment status, families living in poverty, minimum completion of high school/General Educational Development (GED) credential, and industrial businesses by census tract., Results: The location of cannabis retailers was significantly associated with AP in all adjusted models ( p < .005). The percentage of racial/ethnic minorities, age (18-34 years), and nonlicensure of cannabis retailers, which were positively correlated with AP ( p < .05), confounded the association between AP and cannabis retailer location., Conclusions: The concentration of unlicensed cannabis retailers and tobacco retailers in young and racially/ethnically diverse neighborhoods may increase access to and use of cigarillos for blunt smoking. Jurisdictions within Los Angeles County should consider passing ordinances requiring minimum distances between cannabis and tobacco retailers., Competing Interests: No conflicts are declared by the authors.

Background: Spatial variability of COVID-19 cases may suggest geographic disparities of social determinants of health. Spatial analyses of population-level data may provide insight on factors that may contribute to COVID-19 transmission, hospitalization, and death., Methods: Generalized additive models were used to map COVID-19 risk from March 2020 to February 2021 in Orange County (OC), California. We geocoded and analyzed 221,843 cases to OC census tracts within a Poisson framework while smoothing over census tract centroids. Location was randomly permuted 1000 times to test for randomness. We also separated the analyses temporally to observe if risk changed over time. COVID-19 cases, hospitalizations, and deaths were mapped across OC while adjusting for population-level demographic data in crude and adjusted models., Results: Risk for COVID-19 cases, hospitalizations, and deaths were statistically significant in northern OC. Adjustment for demographic data substantially decreased spatial risk, but areas remained statistically significant. Inclusion of location within our models considerably decreased the magnitude of risk compared to univariate models. However, percent minority (adjusted RR: 1.06, 95%CI: 1.06, 1.07), average household size (aRR: 1.06, 95%CI: 1.05, 1.07), and percent service industry (aRR: 1.05, 95%CI: 1.04, 1.06) remained significantly associated with COVID-19 risk in adjusted spatial models. In addition, areas of risk did not change between surges and risk ratios were similar for hospitalizations and deaths., Conclusion: Significant risk factors and areas of increased risk were identified in OC in our adjusted models and suggests that social and environmental factors contribute to the spread of COVID-19 within communities. Areas in north OC remained significant despite adjustment, but risk substantially decreased. Additional investigation of risk factors may provide insight on how to protect vulnerable populations in future infectious disease outbreaks., (© 2022. The Author(s).)

Background: Prenatal exposure to drinking water with arsenic concentrations >50 μg/L is associated with adverse birth outcomes, with inconclusive evidence for concentrations ≤50 μg/L. In a collaborative effort by public health experts, hydrologists, and geologists, we used published machine learning model estimates to characterize arsenic concentrations in private wells-federally unregulated for drinking water contaminants-and evaluated associations with birth outcomes throughout the conterminous U.S., Methods: Using several machine learning models, including boosted regression trees (BRT) and random forest classification (RFC), developed from measured groundwater arsenic concentrations of ∼20,000 private wells, we characterized the probability that arsenic concentrations occurred within specific ranges in groundwater. Probabilistic model estimates and private well usage data were linked by county to all live birth certificates from 2016 (n = 3.6 million). We evaluated associations with gestational age and term birth weight using mixed-effects models, adjusted for potential confounders and incorporated random intercepts for spatial clustering., Results: We generally observed inverse associations with term birth weight. For instance, when using BRT estimates, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 5 μg/L was associated with a -1.83 g (95% CI: -3.30, -0.38) lower term birth weight after adjusting for covariates. Similarly, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 10 μg/L was associated with a -2.79 g (95% CI: -4.99, -0.58) lower term birth weight. Associations with gestational age were null., Conclusion: In this largest epidemiologic study of arsenic and birth outcomes to date, we did not observe associations of modeled arsenic estimates in private wells with gestational age and found modest inverse associations with term birth weight. Study limitations may have obscured true associations, including measurement error stemming from a lack of individual-level information on primary water sources, water arsenic concentrations, and water consumption patterns., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dirofilaria immitis is the causative agent of canine heartworm disease, a severe health problem in dogs, especially in coastal areas of tropical and subtropical regions of the world. We employed molecular methods to investigate the occurrence of canine infection by filarioids in five municipalities of Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti), a non-endemic area of Rio de Janeiro State, Southeast Brazil. A total of 110 canine blood samples collected from 2017 to 2018 and positive for microfilariae at the modified Knott's test were screened by cPCR targeting DNA fragments of the 12S rDNA gene for filarial nematodes. Seventy-seven samples (70%) tested positive at the molecular analysis. Of these, 72 were identified as D. immitis and 5 (4.5%) as Acanthocheilonema reconditum. Dirofilaria repens was not detected in the studied municipalities of Baixada Fluminense. This is the first record of D. immitis and A. reconditum in the Baixada Fluminense region, Rio de Janeiro State, Brazil. The prevalence of D. immitis cases in the five municipalities suggests the establishment and maintenance of its enzootic cycle in the studied region, which indicate vulnerability to the occurrence of epidemic cycles and, possibly, human cases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The etiologies of major birth defects are still unclear and few spatial analyses have been conducted in the United States. Spatial analyses of individual-level data can help elucidate environmental and social risk factors., Methods: We used generalized additive models to analyze 52,955 cases of neural tube defects, congenital heart defects (CHDs), gastroschisis, and orofacial cleft defects, and sampled from 642,399 controls born between 1999 and 2011 in Texas. The effect of geographic location was measured using a bivariable smooth term of geocoded birth address within a logistic regression framework. We calculated and mapped odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects subtypes across Texas, and adjusted for maternal characteristics, environmental indicators, and community-level covariates. We also performed time-stratified spatiotemporal analyses for more prevalent birth defects., Results: Location was significantly associated with crude odds of all birth defects except hypoplastic left heart syndrome. After adjusting for maternal characteristics, environmental indicators, and community-level factors, ORs in many geographic areas were no longer statistically significant for most defects, especially CHDs. However, areas of significant and insignificant elevated risk remained for defects in all groups in North and South Texas, with ORs for ventricular septal defects increasing over time. Low risk of birth defects was often present in the northern part of East Texas., Conclusion: Significant spatial patterns of birth defects were identified and varied depending on adjustment of different categories of covariates. Further investigation of areas with increased risks may aid in our understanding of birth defects., (© 2021 Wiley Periodicals LLC.)

Objective: To examine whether exposure to ambient ozone, particulate matter with diameter less than 2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and distance to major roadways (DTR) impact ovarian cancer-specific survival, while considering differences by stage, race/ethnicity, and socioeconomic status., Methods: Women diagnosed with epithelial ovarian cancer from 1996 to 2014 were identified through the California Cancer Registry and followed through 2016. Women's geocoded addresses were linked to pollutant exposure data and averaged over the follow-up period. Pollutants were considered independently and in multi-pollutant models. Cox proportional hazards models assessed hazards of disease-specific death due to environmental exposures, controlling for important covariates, with additional models stratified by stage at diagnosis, race/ethnicity and socioeconomic status., Results: PM 2.5 and NO 2 , but not ozone or DTR, were significantly associated with survival in univariate models. In a multi-pollutant model for PM 2.5 , ozone, and DTR, an interquartile range increase in PM 2.5 (Hazard Ratio [HR], 1.45; 95% Confidence Interval [CI], 1.41-1.49) was associated with worse prognosis. Similarly, in the multi-pollutant model with NO 2 , ozone, and DTR, women with higher NO 2 exposures (HR for 20.0-30.0 ppb, 1.30; 95% CI, 1.25-1.36 and HR for >30.0 ppb, 2.48; 95% CI, 2.32-2.66) had greater mortality compared to the lowest exposed (<20.0 ppb). Stratified results show the effects of the pollutants differed by race/ethnicity and were magnified among women diagnosed in early stages., Conclusions: Our analyses suggest that greater exposure to NO 2 and PM 2.5 may adversely impact ovarian cancer-specific survival, independent of sociodemographic and treatment factors. These findings warrant further study., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We conducted a detailed analysis of coronavirus disease in a large population center in southern California, USA (Orange County, population 3.2 million), to determine heterogeneity in risks for infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the actual burden of disease and testing intensity, test positivity, and mortality. In the first month of the local epidemic (March 2020), case incidence clustered in high-income areas. This pattern quickly shifted, and cases next clustered in much higher rates in the north-central area of the county, which has a lower socioeconomic status. Beginning in April 2020, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race or ethnicity, and ZIP codes with low educational attainment) strongly affected risk for seropositivity and death.

The carcinogenicity of perfluorooctanoic acid (PFOA) has been reviewed previously by several different regulatory agencies and researchers, with contradictory conclusions-especially regarding epidemiological findings on kidney cancer and testicular cancer. In addition, previous dose-response assessments have focused primarily on evidence from animal studies. This critical review summarizes peer reviewed epidemiological studies on PFOA and cancers of the kidneys and testes, using modified Hill's criteria to assess the evidence for causation. We converted exposures to a common scale based on serum PFOA concentrations and applied meta-analysis to estimate the average increase in cancer risk reported by the studies with sufficient information to estimate serum PFOA. Using random effects meta-analysis, we found that the average relative increase in cancer risk per 10 ng/mL increase in serum PFOA for these studies is 16% (95% CI: 3%, 30%) for kidney cancer and 3% (95% CI: 2%, 4%) for testicular cancer. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. Implications : Our review meta-analysis indicates an average increase in cancer risk per 10 ng/mL increase in serum PFOA for kidney and testicular cancers. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. The weight of evidence could be even stronger with the addition of future studies conducted in large cohorts.

Unconventional natural gas developments (UNGD) may release air and water pollutants into the environment, potentially increasing the risk of birth defects. We conducted a case-control study evaluating 52,955 cases with birth defects and 642,399 controls born between 1999 and 2011 to investigate the relationship between UNGD exposure and the risk of gastroschisis, congenital heart defects (CHD), neural tube defects (NTDs), and orofacial clefts in Texas. We calculated UNGD densities (number of UNGDs per area) within 1, 3, and 7.5 km of maternal address at birth and categorized exposure by density tertiles. For CHD subtypes with large case numbers, we also performed time-stratified analyses to examine temporal trends. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association with UNGD exposure, accounting for maternal characteristics and neighborhood factors. We also included a bivariable smooth of geocoded maternal location in an additive model to account for unmeasured spatially varying risk factors. Positive associations were observed between the highest tertile of UNGD density within 1 km of maternal address and risk of anencephaly (aOR: 2.44, 95% CI: 1.55, 3.86), spina bifida (aOR: 2.09, 95% CI: 1.47, 2.99), gastroschisis among older mothers (aOR: 3.19, 95% CI: 1.77, 5.73), aortic valve stenosis (aOR: 1.90, 95% CI: 1.33, 2.71), hypoplastic left heart syndrome (aOR: 2.00, 95% CI: 1.39, 2.86), and pulmonary valve atresia or stenosis (aOR: 1.36, 95% CI: 1.10, 1.66). For CHD subtypes, results did not differ substantially by distance from maternal address or when residual confounding was considered, except for atrial septal defects. We did not observe associations with orofacial clefts. Our results suggest that UNGDs were associated with some CHDs and possibly NTDs. In addition, we identified temporal trends and observed presence of spatial residual confounding for some CHDs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Children's prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking., Objective: Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5865 girls (1st generation) born in southeast Massachusetts from 1992-1998., Methods: Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ'-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant's birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n = 371)., Results: The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95 th percentile of the HCB and PCB exposure distributions (OR = 3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth., Significance: Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

Clinic-based estimates of SARS-CoV-2 may considerably underestimate the total number of infections. Access to testing in the US has been heterogeneous and symptoms vary widely in infected persons. Public health surveillance efforts and metrics are therefore hampered by underreporting. We set out to provide a minimally biased estimate of SARS-CoV-2 seroprevalence among adults for a large and diverse county (Orange County, CA, population 3.2 million). We implemented a surveillance study that minimizes response bias by recruiting adults to answer a survey without knowledge of later being offered SARS-CoV-2 test. Several methodologies were used to retrieve a population-representative sample. Participants (n = 2979) visited one of 11 drive-thru test sites from July 10th to August 16th, 2020 (or received an in-home visit) to provide a finger pin-prick sample. We applied a robust SARS-CoV-2 Antigen Microarray technology, which has superior measurement validity relative to FDA-approved tests. Participants include a broad age, gender, racial/ethnic, and income representation. Adjusted seroprevalence of SARS-CoV-2 infection was 11.5% (95% CI: 10.5-12.4%). Formal bias analyses produced similar results. Prevalence was elevated among Hispanics (vs. other non-Hispanic: prevalence ratio [PR] = 1.47, 95% CI 1.22-1.78) and household income < $50,000 (vs. > $100,000: PR = 1.42, 95% CI: 1.14 to 1.79). Results from a diverse population using a highly specific and sensitive microarray indicate a SARS-CoV-2 seroprevalence of ~ 12 percent. This population-based seroprevalence is seven-fold greater than that using official County statistics. In this region, SARS-CoV-2 also disproportionately affects Hispanic and low-income adults.

Background: Early life exposure to neurotoxicants and non-chemical psychosocial stressors can impede development of prefrontal cortical functions that promote behavioral regulation and thereby may predispose to adolescent risk-taking related behaviors (e.g., substance use or high-risk sexual activity). This is particularly concerning for communities exposed to multiple stressors., Methods: This study examined the relation of exposure to mixtures of chemical stressors, non-chemical psychosocial stressors, and other risk factors with neuropsychological correlates of risk-taking. Specifically, we assessed psychometric measures of both adverse behavioral regulation and adaptive attributes among adolescents (age ∼ 15 years) in the New Bedford Cohort (NBC), a sociodemographically diverse cohort of 788 children born 1993-1998 to mothers residing near the New Bedford Harbor Superfund site. The NBC includes biomarkers of prenatal exposure to organochlorines and metals; sociodemographic, parental and home characteristics; and periodic neurodevelopmental assessments. We modelled exposure mixtures using multi-dimensional smooths within generalized additive models., Results: Children of younger mothers with lower IQ who were exposed prenatally to higher polychlorinated biphenyls and lead had poorer anger control. This pattern was not apparent for children of older mothers with higher IQs. Direction of associations between increased hyperactivity and prenatal levels of organochlorine mixtures differed by maternal age and depression symptoms. Higher cord blood Pb levels, in conjunction with poorer HOME scores, were associated with poorer self-esteem when mothers had fewer depression symptoms., Conclusions: Analyses suggest that prenatal chemical exposures and non-chemical factors interact to contribute to neuropsychological correlates of risk-taking behaviors in adolescence. By simultaneously considering multiple factors associated with adverse behavioral regulation, we identified potential high-risk combinations that reflect both chemical and psychosocial stressors amenable to intervention., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Generalized additive models (GAMs) with bivariate smoothers are frequently used to map geographic disease risks in epidemiology studies. A challenge in identifying health disparities has been the lack of intuitive and computationally feasible methods to assess whether the pattern of spatial effects varies over time. In this research, we accommodate time-stratified smoothers into the GAM framework to estimate time-specific spatial risk patterns while borrowing information from confounding effects across time. A backfitting algorithm for model estimation is proposed along with a permutation testing framework for assessing temporal heterogeneity of geospatial risk patterns across two or more time points. Simulation studies show that our proposed permuted mean squared difference (PMSD) test performs well with respect to type I error and power in various settings when compared with existing methods. The proposed model and PMSD test are used geospatial risk patterns of patent ductus arteriosus (PDA) in the state of Massachusetts over 2003-2009. We show that there is variation over time in spatial patterns of PDA risk, adjusting for other known risk factors, suggesting the presence of potential time-varying and space-related risk factors other than the adjusted ones., (© 2020 John Wiley & Sons Ltd.)

Background: Evidence suggests that geographic location may independently contribute to ovarian cancer survival. We aimed to investigate how the association between residential location and ovarian cancer-specific survival in California varies by race/ethnicity and socioeconomic status., Methods: Additive Cox proportional hazard models were used to predict hazard ratios (HRs) and 95% confidence intervals (CI) for the association between geographic location throughout California and survival among 29,844 women diagnosed with epithelial ovarian cancer between 1996 and 2014. We conducted permutation tests to determine a global P-value for significance of location. Adjusted analyses considered distance traveled for care, distance to closest high-quality-of-care hospital, and receipt of National Comprehensive Cancer Network guideline care. Models were also stratified by stage, race/ethnicity, and socioeconomic status., Results: Location was significant in unadjusted models (P = 0.009 among all stages) but not in adjusted models (P = 0.20). HRs ranged from 0.81 (95% CI: 0.70, 0.93) in Southern Central Valley to 1.41 (95% CI: 1.15, 1.73) in Northern California but were attenuated after adjustment (maximum HR = 1.17, 95% CI: 1.08, 1.27). Better survival was generally observed for patients traveling longer distances for care. Associations between survival and proximity to closest high-quality-of-care hospitals were null except for women of lowest socioeconomic status living furthest away (HR = 1.22, 95% CI: 1.03, 1.43)., Conclusions: Overall, geographic variations observed in ovarian cancer-specific survival were due to important predictors such as receiving guideline-adherent care. Improving access to expert care and ensuring receipt of guideline-adherent treatment should be priorities in optimizing ovarian cancer survival., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Dioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed., Objectives: To prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses' Health Study II (NHSII)., Methods: NHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: From 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status., Discussion: Results from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Effective place-based interventions for childhood obesity call for the recognition of the high-risk neighbourhoods and an understanding of the determinants present locally. However, such an approach is uncommon. In this study, we identified neighbourhoods with elevated prevalence of childhood obesity ('hotspots') in the Porto Metropolitan Area and investigated to what extent the socio-economic and built environment characteristics of the neighbourhoods explained such hotspots., Methods: We used data on 5203 7-year-old children from a population-based birth cohort, Generation XXI. To identify hotspots, we estimated local obesity odds ratios (OR) and 95% confidence intervals (95%CI) using generalized additive models with a non-parametric smooth for location. Measures of the socio-economic and built environment were determined using a Geographic Information System. Associations between obesity and neighbourhood characteristics were expressed as OR and 95%CI after accounting for individual-level variables., Results: At 7 years of age, 803 (15.4%) children were obese. The prevalence of obesity varied across neighbourhoods and two hotspots were identified, partially explained by individual-level variables. Adjustment for neighbourhood characteristics attenuated the ORs and further explained the geographic variation. This model revealed an association between neighbourhood socio-economic deprivation score and obesity (OR = 1.014, 95%CI 1.004-1.025), as well as with the presence of fast-food restaurants at a walkable distance from the residence (OR = 1.37, 1.06-1.77)., Conclusions: In our geographic area it was possible to identify neighbourhoods with elevated prevalence of childhood obesity and to suggest that targeting such high-priority neighbourhoods and their environmental characteristics may help reduce childhood obesity., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Tetrachloroethylene (PCE) is a common contaminant in both occupational and community settings. High exposure levels in the workplace have been shown to have adverse impacts on reproduction and development but few epidemiological studies have examined these effects at the lower levels commonly seen in community settings. We were presented with a unique opportunity to examine the reproductive and developmental effects of prenatal exposure to PCE-contaminated drinking water resulting from the installation of vinyl-lined water pipes in Massachusetts and Rhode Island from the late 1960s through 1980. This review describes the methods and findings of two community-based epidemiological studies, places their results in the context of the existing literature, and describes the strengths and challenges of conducting epidemiological research on a historical pollution episode. Our studies found that prenatal exposure to PCE-contaminated drinking water is associated with delayed time-to-pregnancy, and increased risks of placental abruption, stillbirths stemming from placental dysfunction, and certain birth defects. No associations were observed with pregnancy loss, birth weight, and gestational duration. Important strengths of this research included the availability of historical data on the affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little opportunity for recall bias and confounding. Challenges arose mainly from the retrospective nature of the exposure assessments. This research highlights the importance of considering pregnant women and their developing fetuses when monitoring, regulating, and remediating drinking water contaminants.

Objective: To validate the observed/expected ratio for adherence to ovarian cancer treatment guidelines as a risk-adjusted measure of hospital quality care, and to identify patient characteristics associated with disparities in access to high-performing hospitals., Methods: This was a retrospective population-based study of stage I-IV invasive epithelial ovarian cancer reported to the California Cancer Registry between 1996 and 2014. A fit logistic regression model, which was risk-adjusted for patient and disease characteristics, was used to calculate the observed/expected ratio for each hospital, stratified by hospital annual case volume. A Cox proportional hazards model was used for survival analyses, and a multivariable logistic regression model was used to identify independent predictors of access to high-performing hospitals., Results: The study population included 30,051 patients who were treated at 426 hospitals: low observed/expected ratio (n=304) 23.5% of cases; intermediate observed/expected ratio (n=92) 57.8% of cases; and high observed/expected ratio (n=30) 18.7% of cases. Hospitals with high observed/expected ratios were significantly more likely to deliver guideline-adherent care (53.3%), compared with hospitals with intermediate (37.8%) and low (27.5%) observed/expected ratios (P<.001). Median disease-specific survival time ranged from 73.0 months for hospitals with high observed/expected ratios to 48.1 months for hospitals with low observed/expected ratios (P<.001). Treatment at a hospital with a high observed/expected ratio was an independent predictor of superior survival compared with hospitals with intermediate (hazard ratio [HR] 1.06, 95% CI 1.01-1.11, P<.05) and low (HR 1.10, 95% CI 1.04-1.16, P<.001) observed/expected ratios. Being of Hispanic ethnicity (odds ratio [OR] 0.85, 95% CI 0.78-0.93, P<.001, compared with white), having Medicare insurance (OR 0.74, 95% CI 0.68-0.81 P<.001, compared with managed care), having a Charlson Comorbidity Index score of 2 or greater (OR 0.91, 95% CI 0.83-0.99, P<.05), and being of lower socioeconomic status (lowest quintile OR 0.41, 95% CI 0.36-0.46, P<.001, compared with highest quintile) were independent negative predictors of access to a hospital with a high observed/expected ratio., Conclusion: Ovarian cancer care at a hospital with a high observed/expected ratio is an independent predictor of improved survival. Barriers to high-performing hospitals disproportionately affect patients according to sociodemographic characteristics. Triage of patients with suspected ovarian cancer according to a performance-based observed/expected ratio hospital classification is a potential mechanism for expanded access to expert care.

Background: Evidence of geographic disparities in breast cancer incidence within the U.S. and spatial analyses can provide insight into the potential contribution of environmental exposures or other geographically-varying factors to these disparities., Methods: We applied generalized additive models (GAMs) to smooth geocoded residential coordinates while adjusting for covariates. Our analysis included 3,478 breast cancer cases among 24,519 control women from the Nurses' Health Study II (NHSII). We first examined associations with residential location during adolescence (high school address) or early adulthood (address in 1991). We then assessed the contribution from known individual-level risk factors, measures of socioeconomic status (SES), and occupational and environmental factors that vary spatially and have been linked to breast cancer. Secondary analyses by estrogen receptor (ER) and menopausal status were also conducted., Results: We identified geographic patterns of breast cancer risk associated with location during adolescence, with increased risk apparent in Michigan, the Northwest, and the New York City area, that shifted to southern New England when addresses during early adulthood were analyzed. Similar results were observed after adjustment for individual- and area-level factors, although spatial associations were no longer statistically significant., Conclusion: Breast cancer risk is not spatially uniform across the U.S. and incidence patterns varied depending on the timing during life of the residence considered. Geographic disparities persisted even after accounting for established and suspected breast cancer risk factors, suggesting that unmeasured environmental or lifestyle risk factors may explain geographic variation in risk in different parts of the country., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest.

Background: More than 14,000 women in the United States die of ovarian cancer (OC) every year. Disparities in survival have been observed by race and socioeconomic status (SES), and vary spatially even after adjusting for treatment received. This study aimed to determine the impact of geographic location on receiving treatment adherent to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for OC, independent of other predictors., Patients and Methods: Women diagnosed with all stages of epithelial OC (1996-2014) were identified through the California Cancer Registry. Generalized additive models, smoothing for residential location, were used to calculate adjusted odds ratios (ORs) and 95% CIs for receiving nonadherent care throughout California. We assessed the impact of distance traveled for care, distance to closest high-quality hospital, race/ethnicity, and SES on receipt of quality care, adjusting for demographic and cancer characteristics and stratifying by disease stage., Results: Of 29,844 patients with OC, 11,419 (38.3%) received guideline-adherent care. ORs for nonadherent care were lower in northern California and higher in Kern and Los Angeles counties. Magnitudes of associations with location varied by stage (OR range, 0.45-2.19). Living farther from a high-quality hospital increased the odds of receiving nonadherent care (OR, 1.18; 95% CI, 1.07-1.29), but travel >32 km to receive care was associated with decreased odds (OR, 0.76; 95% CI, 0.70-0.84). American Indian/other women were more likely to travel greater distances to receive care. Women in the highest SES quintile, those with Medicare insurance, and women of non-Hispanic black race were less likely to travel far. Patients who were Asian/Pacific Islander lived the closest to a high-quality hospital., Conclusions: Among California women diagnosed with OC, living closer to a high-quality center was associated with receiving adherent care. Non-Hispanic black women were less likely to receive adherent care, and women with lower SES lived farthest from high-quality hospitals. Geographic location in California is an independent predictor of adherence to NCCN Guidelines for OC.

Background: Children born near New Bedford, Massachusetts, have been prenatally exposed to multiple environmental chemicals, in part due to an older housing stock, maternal diet, and proximity to the New Bedford Harbor (NBH) Superfund site. Chemical exposure measures are not available for all births, limiting epidemiologic investigations and potential interventions., Objective: We linked biomonitoring data from the New Bedford Cohort (NBC) and birth record data to predict prenatal exposures for all contemporaneous area births., Methods: We used prenatal exposure biomarker data from the NBC, a population-based cohort of 788 mother-infant pairs born during 1993–1998 to mothers living near the NBH, linked to their corresponding Massachusetts birth record data, to build predictive models for cord serum polychlorinated biphenyls (expressed as a sum, [Formula: see text]), [Formula: see text] (DDE), hexachlorobenzene (HCB), cord blood lead (Pb), and maternal hair mercury (Hg). We applied the best fit models (highest pseudo [Formula: see text]), with multivariable smooths of continuous variables, to predict exposure biomarkers for all 10,270 births during 1993–1998 around the NBH. We used 10-fold cross validation to validate the exposure models and the bootstrap method to characterize sampling variability in the exposure predictions., Results: The 10-fold cross-validated [Formula: see text] for the [Formula: see text], DDE, HCB, Pb, and Hg exposure models were 0.54, 0.40, 0.34, 0.46, and 0.40, respectively. For each exposure model, multivariable smooths of continuous variables improved the fit compared with linear models. Other variables with significant effects on exposure estimates were paternal education, maternal race/ethnicity, and maternal ancestry. The resulting exposure predictions for all births had variability consistent with the NBC measured exposures., Conclusions: Predictive models using multivariable smoothing explained reasonable amounts of variance in prenatal exposure biomarkers. Our analyses suggest that prenatal chemical exposures can be predicted for all contemporaneous births in the same geographic area by modeling available biomarker data for a subset of that population. https://doi.org/10.1289/EHP4849.

Small geographic areas with lower mammography screening participation rates may reflect gaps in screening efforts. Our objective was to use spatial analyses to understand disparities in mammography screening use and to identify factors to increase its uptake in areas that need it in Lyon metropolitan area, France. Data for screened women between the ages of 50 and 74 were analyzed. Census blocks of screened and non screened women were extracted from the mammography screening programme 2015-2016 dataset. We used spatial regression models, within a generalized additive framework to determine clusters of census blocks with significantly higher prevalence of non-participation of mammography screening. Smoothed risk maps were crude and adjusted on the following covariates: deprivation index and opportunistic screening. Among 178,002 women aged 50 to 74, 49.9% received mammography screening. As hypothesized, women living in highly deprived census blocks had lower participation rates compared to less deprived blocks, 45.2% vs. 51.4% p < 0.001. Spatial analyses identified four clusters, one located in an urban area and three in suburban areas. Moreover, depending on the location of the cluster, the influence came from different variables. Knowing the impact of site-specific risk factors seems to be important for implementing an appropriate prevention intervention.

Background: Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results., Methods: The Nurses' Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00, 95% CI: 0.90, 1.11, p for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER- breast cancer and early-life UV exposure at birth (adjusted HR = 0.94, 95% CI: 0.88, 1.01 per interquartile range increase [15.7 mW/m 2 ]), age 15 (adjusted HR = 0.96, 95% CI: 0.89, 1.04 per 18.0 mW/m 2 ), and age 30 (adjusted HR = 0.90, 95% CI: 0.82, 1.00 per 27.7 mW/m 2 )., Conclusions: Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER- breast cancer risk., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest.

Background: Residents of Massachusetts and Rhode Island were exposed to tetrachloroethylene-contaminated drinking water from 1968 through the early 1990s when it leached from the vinyl lining of asbestos cement water distribution pipes. While occupational exposure to solvents during pregnancy has consistently been linked to an increased risk of certain birth defects, mixed results have been observed for environmental sources of exposure, including contaminated drinking water. The present case-control study was undertaken to examine further the association between prenatal exposure to tetrachloroethylene-contaminated drinking water and the risk of central nervous system defects, oral clefts and hypospadias., Methods: Cases were comprised of live- and stillborn infants delivered between 1968 and 1995 to mothers who resided in 28 Massachusetts and Rhode Island cities and towns with some PCE-contaminated water supplies. Infants with central nervous system defects (N = 268), oral clefts (N = 112) and hypospadias (N = 94) were included. Controls were randomly selected live-born, non-malformed infants who were delivered during the same period and geographic area as cases (N = 771). Vital records and self-administered questionnaires were used to gather identifying information, birth defect diagnoses, and other relevant data. PCE exposure during the first trimester was estimated using water distribution system modeling software that incorporated a leaching and transport model. Prenatal PCE exposure was dichotomized as "high" or "low" exposure at the level corresponding to an estimated average concentration of 40 μg/L, the criterion for remediation when PCE contamination was discovered in 1980., Results: Mothers with "high" levels of exposure to PCE-contaminated drinking water during the first trimester (> 40 μg/L) had increased odds of having a child with spina bifida (OR: 2.0, 95% CI: 0.8-5.4), cleft lip with or without cleft palate (OR: 3.8, 95% CI: 1.2-12.3) and hypospadias (OR: 2.1, 95% CI:0.5-8.3). No increases in the odds of other defects were observed in relation to "high" exposure levels., Conclusions: The results of the present study suggest that mothers with "high" PCE exposure levels during the first trimester have increased odds of having a child with spina bifida, cleft lip with or without cleft palate, and hypospadias. These findings support several prior studies that observed an increased risk of selected birth defects following prenatal exposure to solvents in occupational and environmental settings. Even though PCE contamination from vinyl lined pipes was remediated many years ago, it remains a widespread contaminant across the U.S and so environmental regulations must be guided by a precautionary perspective that safeguards pregnant women and their offspring.

Background: The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts., Methods: The Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results., Results: Any cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76)., Conclusions: We found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Residents of Massachusetts and Rhode Island were exposed to tetrachloroethylene (PCE)-contaminated drinking water from 1968 through the early 1990s when the solvent was used to apply a vinyl liner to drinking water mains to address taste and odor problems. Few studies have examined the risk of fetal death among women exposed to solvent-contaminated drinking water. Two previous investigations found moderate increases in the risk of stillbirth among highly exposed women; however, these results were based on a small number of cases. The present case-control study was undertaken to examine further this association with a large number of stillbirths., Methods: Cases were comprised of stillborn infants delivered between 1968 and 1995 to mothers who resided in 28 Massachusetts and Rhode Island cities and towns with some affected water mains (N = 296). Cases were included if the cause of death was placental abruption and/or placental insufficiency. Controls were randomly selected live-born infants who were delivered in the same time period and geographic area (N = 783). Data on confounding variables were gathered from vital records and questionnaires. PCE exposure was estimated using a leaching and transport model integrated into water system software., Results: Mothers with any PCE exposure had a 1.7-fold increase in the adjusted odds of placenta-related stillbirth (95% CI: 1.2-2.4). The adjusted odds ratio (OR) increased as a woman's exposure level increased: in comparison to unexposed mothers, ORs were 1.5 (95% CI: 1.0-2.3) for low exposure (> 0-median), 1.7 (95% CI: 1.1-2.5) for moderate exposure (>median-90th percentile) and 1.9 (95% CI: 1.1-3.2) for high exposure (>90th percentile) (p value for trend = 0.02). A similar pattern was observed when PCE exposure was dichotomized at 40 μg/L, the suggested action guideline for remediation (OR = 1.5, 95% CI: 1.1-2.2 and OR = 2.6, 95% CI: 1.4-4.8, respectively, for PCE exposure <=40 μg/L and > 40 μg/L) (p value for trend = .003)., Conclusions: We observed a linear dose-dependent increase in the odds of stillbirth due to placental abruption and placental insufficiency with prenatal exposure to PCE contaminated drinking water. Because PCE remains a common drinking water contaminant, these findings highlight the importance of considering pregnant women when monitoring, regulating and remediating drinking water supplies.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5 µm or less (PM 2.5 ) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM 2.5 was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m 3 increase in PM 2.5. We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM 2.5 exposure 1 day (OR = 1.07, 95% CI = 1.03-1.11) and 4 days (OR = 1.04, 95% CI = 0.99-1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR = 1.17, 95% CI = 1.08-1.28) and otitis media 4 and 7 days prior to clinical encounter (OR = 1.09, 95% CI = 1.02-1.16 and OR = 1.08, 95% CI = 1.02-1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM 2.5 exposures.

Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor neuron with very few known risk factors. We conducted a spatial epidemiologic analysis of ALS incidence in Denmark to assess the contribution of sociodemographic determinants to geographic variation., Methods: We analyzed 4249 ALS cases (1982-2013), each with 100 controls matched on sex and birth year. Odds ratio and 95% confidence bands at birth and diagnosis/index locations were calculated using generalized additive models. We included a bivariate spatial smooth for location in our conditional logistic regression adjusted for socioeconomic status and marital status. We also conducted analyses adjusted for both birth and diagnosis addresses to separate location effects., Results: We observed significantly elevated ALS odds near Copenhagen for both the birth and diagnosis period analyses. Sociodemographic factors did not explain the observed patterns. When we further adjusted our spatial analyses by including both birth and diagnosis addresses, the significant area of elevated male ALS odds by birth address shifted to northwest Denmark away from Copenhagen, and there was little evidence of variation among women. Geographic variation at diagnosis differed between male and females, suggesting that patterns are not just due to regional variation in case ascertainment., Conclusion: ALS incidence in Denmark is associated with both location at birth and diagnosis, suggesting that geographic variation may be due to exposures occurring at birth or closer to diagnosis, although the latter could relate to case ascertainment issues.

Background: Findings from a recent prospective cohort study in California suggested increased risk of breast cancer associated with higher exposure to certain carcinogenic and estrogen-disrupting hazardous air pollutants (HAPs). However, to date, no nationwide studies have evaluated these possible associations. Our objective was to examine the impacts of mammary carcinogen and estrogen disrupting HAPs on risk of invasive breast cancer in a nationwide cohort., Methods: We assigned HAPs from the US Environmental Protection Agency's 2002 National Air Toxics Assessment to 109,239 members of the nationwide, prospective Nurses' Health Study II (NHSII). Risk of overall invasive, estrogen receptor (ER)-positive (ER+), and ER-negative (ER-) breast cancer with increasing quartiles of exposure were assessed in time-varying multivariable proportional hazards models, adjusted for traditional breast cancer risk factors., Results: A total of 3321 invasive cases occurred (2160 ER+, 558 ER-) during follow-up 1989-2011. Overall, there was no consistent pattern of elevated risk of the HAPs with risk of breast cancer. Suggestive elevations were only seen with increasing 1,2-dibromo-3-chloropropane exposures (multivariable adjusted HR of overall breast cancer = 1.12, 95% CI: 0.98-1.29; ER+ breast cancer HR = 1.09; 95% CI: 0.92, 1.30; ER- breast cancer HR = 1.14; 95% CI: 0.81, 1.61; each in the top exposure quartile compared to the lowest)., Conclusions: Exposures to HAPs during adulthood were not consistently associated with an increased risk of overall or estrogen-receptor subtypes of invasive breast cancer in this nationwide cohort of women.

After publication of the article [1], it was brought to our attention that a number in Table 1 is incorrect.

Background: Associations between ambient particulate matter < 2.5 μm (PM 2.5 ) and asthma morbidity have been suggested in previous epidemiologic studies but results are inconsistent for areas with lower PM 2.5 levels. We estimated the associations between early-life short-term PM 2.5 exposure and the risk of asthma or wheeze clinical encounters among Massachusetts children in the innovative Pregnancy to Early Life Longitudinal (PELL) cohort data linkage system., Methods: We used a semi-bidirectional case-crossover study design with short-term exposure lags for asthma exacerbation using data from the PELL system. Cases included children up to 9 years of age who had a hospitalization, observational stay, or emergency department visit for asthma or wheeze between January 2001 and September 2009 (n = 33,387). Daily PM 2.5 concentrations were estimated at a 4-km resolution using satellite remote sensing, land use, and meteorological data. We applied conditional logistic regression models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We also stratified by potential effect modifiers., Results: The median PM 2.5 concentration among participants was 7.8 μg/m 3 with an interquartile range of 5.9 μg/m 3 . Overall, associations between PM 2.5 exposure and asthma clinical encounters among children at lags 0, 1 and 2 were close to the null value of OR = 1.0. Evidence of effect modification was observed by birthweight for lags 0, 1 and 2 (p < 0.05), and season of clinical encounter for lags 0 and 1 (p < 0.05). Children with low birthweight (LBW) (< 2500 g) had increased odds of having an asthma clinical encounter due to higher PM 2.5 exposure for lag 1 (OR: 1.08 per interquartile range (IQR) increase in PM 2.5 ; 95% CI: 1.01, 1.15)., Conclusion: Asthma or wheeze exacerbations among LBW children were associated with short-term increases in PM 2.5 concentrations at low levels in Massachusetts.

Data indicate that the prevalence of autism spectrum disorder (ASD) may be increasing and that it varies geographically. We investigated associations between residential location and ASD in the children of Nurses' Health Study II (United States) participants in order to generate hypotheses about social and environmental factors related to etiology or diagnosis. Analyses included data on 13,507 children born during 1989-1999 (486 with ASD). We explored relationships between ASD and residential location both at birth and at age 6 years (i.e., closer to average age at diagnosis). Generalized additive models were used to predict ASD odds across the United States. Children born in New England were 50% more likely to be diagnosed with ASD compared with children born elsewhere in the United States. Patterns were not explained by geographic variation in maternal age, birth year, child's sex, community income, or prenatal exposure to hazardous air pollutants, indicating that spatial variation is not attributable to these factors. Using the residential address at age 6 years produced similar results; however, areas of significantly decreased ASD odds were observed in the Southeast, where children were half as likely to have ASD. These results may indicate that diagnostic factors are driving spatial patterns; however, we cannot rule out the possibility that other environmental factors are influencing distributions., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic particulate matter less than 2.5μm in diameter (PM 2.5 ) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM 2.5 exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n=18,029) and OM (n=40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m 3 increase in lifetime average satellite based PM 2.5 exposure . Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM 2.5 was not associated with infant bronchiolitis (OR=1.02, 95% CI=1.00, 1.04) and inversely associated with OM (OR=0.97, 95% CI=0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR=1.23, 95% CI=1.14, 1.31) but not OM (OR=0.98, 95% CI=0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM 2.5 exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Ovarian cancer survival varies geographically throughout California. The objective of this study is to determine the impact of living in disadvantaged communities on spatial patterns of survival disparities. Including a bivariate spatial smooth of geographic location within the Cox proportional hazard models is an effective approach for spatial analyses of cancer survival. Women diagnosed with advanced Stage IIIC/IV epithelial ovarian cancer (1996-2006) were identified from the California Cancer Registry. The impact of living in disadvantaged communities, as measured by the California Office of Environmental Health Hazard Assessment cumulative CalEnviroScreen 2.0 score, on geographic disparities in survival was assessed while controlling for age, tumor characteristics, quality of care, and race. Community-level air quality indicators and socioeconomic status (SES) were also independently examined in secondary analyses. The Cox proportional hazard spatial methods are available in the MapGAM package implemented in R. An increase in the community disadvantage from the 5th (less disadvantage) to the 95th percentile (more disadvantage) was significantly associated with poorer ovarian cancer survival (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.07-1.26). Ozone levels and SES were the most influential indicators on geographic disparities that warrant further investigation. The use of a bivariate smoother of location within the survival model allows for more advanced spatial analyses for exploring potential air quality-related predictors of geographic disparities., (Copyright © 2017. Published by Elsevier Inc.)

Attention-deficit/hyperactivity disorder (ADHD) has an uncertain etiology, with potential contributions from different risk factors such as prenatal environmental exposure to organochlorines and metals, social risk factors, and genetics. The degree to which geographic variability in ADHD is independent of, or explained by, risk factors may provide etiological insight. We investigated determinants of geographic variation in ADHD-related behaviors among children living near the polychlorinated biphenyl-contaminated New Bedford Harbor (NBH) Superfund site in Massachusetts. Participants were 573 children recruited at birth (1993-1998) who were born to mothers residing near the NBH site. We assessed ADHD-related behaviors at age 8 years using Conners' Teacher Rating Scale-Revised: Long Version. Adjusted generalized additive models were used to smooth the association of pregnancy residence with ADHD-related behaviors and assess whether prenatal organochlorine or metal exposures, sociodemographic factors, or other factors explained spatial patterns. Models that adjusted for child's age and sex displayed significantly increased ADHD-related behavior among children whose mothers resided west of the NBH site during pregnancy. These spatial patterns persisted after adjusting for prenatal exposure to organochlorines and metals but were no longer significant after controlling for sociodemographic factors. The findings underscore the value of spatial analysis in identifying high-risk subpopulations and evaluating candidate risk factors., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)