Multiple prenatal exposures and acute-care clinical encounters for asthma among children born to mothers living near a Superfund site.

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.

Role of mammography accessibility, deprivation and spatial effect in breast cancer screening participation in France: an observational ecological study.

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.

Effect of socioeconomic factors during the early COVID-19 pandemic: a spatial analysis.

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.

Predictors of Test Positivity, Mortality, and Seropositivity during the Early Coronavirus Disease Epidemic, Orange County, California, USA.

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.

Ambient air pollution and ovarian cancer survival in California.

OBJECTIVE: To examine whether exposure to ambient ozone, particulate matter with diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2), 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: PM2.5 and NO2, but not ozone or DTR, were significantly associated with survival in univariate models. In a multi-pollutant model for PM2.5, ozone, and DTR, an interquartile range increase in PM2.5 (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 NO2, ozone, and DTR, women with higher NO2 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 NO2 and PM2.5 may adversely impact ovarian cancer-specific survival, independent of sociodemographic and treatment factors. These findings warrant further study.

Birth defects and unconventional natural gas developments in Texas, 1999-2011.

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.

A stratified generalized additive model and permutation test for temporal heterogeneity of smoothed bivariate spatial effects.

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.

Dioxin exposure and breast cancer risk in a prospective cohort study.

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.

Correction to: Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

Following publication of the original article [1], the author reported that, because of a programming error, incorrect sentences and incorrect Table 3 has been published. The correct sentences and Table 3 are shown below.

Contribution of Geographic Location to Disparities in Ovarian Cancer Treatment.

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.

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy.

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.

Correction to: Early-life exposure to PM2.5 and risk of acute asthma clinical encounters among children in Massachusetts: a case-crossover analysis.

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

Early-life exposure to PM2.5 and risk of acute asthma clinical encounters among children in Massachusetts: a case-crossover analysis.

BACKGROUND: Associations between ambient particulate matter < 2.5 µm (PM2.5) and asthma morbidity have been suggested in previous epidemiologic studies but results are inconsistent for areas with lower PM2.5 levels. We estimated the associations between early-life short-term PM2.5 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 PM2.5 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 PM2.5 concentration among participants was 7.8 µg/m3 with an interquartile range of 5.9 µg/m3. Overall, associations between PM2.5 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 PM2.5 exposure for lag 1 (OR: 1.08 per interquartile range (IQR) increase in PM2.5; 95% CI: 1.01, 1.15). CONCLUSION: Asthma or wheeze exacerbations among LBW children were associated with short-term increases in PM2.5 concentrations at low levels in Massachusetts.

Modeled exposure to tetrachloroethylene-contaminated drinking water and the risk of placenta-related stillbirths: a case-control study from Massachusetts and Rhode Island.

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.

Modeled exposure to tetrachloroethylene-contaminated drinking water and the occurrence of birth defects: a case-control study from Massachusetts and Rhode Island.

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.

Exposure to hazardous air pollutants and risk of incident breast cancer in the nurses' health study II.

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.

Spatial Variability in ADHD-Related Behaviors Among Children Born to Mothers Residing Near the New Bedford Harbor Superfund Site.

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.

Geographic Patterns of Autism Spectrum Disorder Among Children of Participants in Nurses' Health Study II.

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.

Impact of community disadvantage and air pollution burden on geographic disparities of ovarian cancer survival in California.

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.

Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.

We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval.