Measuring long-term exposure to wildfire PM2.5 in California: Time-varying inequities in environmental burden.

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM2.5) concentrations differ from relatively smoothly varying total PM2.5. Thus, we introduced a conceptual model for computing long-term wildfire PM2.5 and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM2.5 exposure based on intermittent and extreme daily wildfire PM2.5 concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM2.5 < 5 µg/m3; 2) days with non-zero wildfire PM2.5; 3) mean wildfire PM2.5 during peak exposure week; 4) smoke waves (≥2 consecutive days with <15 µg/m3 wildfire PM2.5); and 5) mean annual wildfire PM2.5 concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM2.5 metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM2.5 exposure for several racial/ethnic groups.

Integrated causal-predictive machine learning models for tropical cyclone epidemiology.

Strategic preparedness reduces the adverse health impacts of hurricanes and tropical storms, referred to collectively as tropical cyclones (TCs), but its protective impact could be enhanced by a more comprehensive and rigorous characterization of TC epidemiology. To generate the insights and tools necessary for high-precision TC preparedness, we introduce a machine learning approach that standardizes estimation of historic TC health impacts, discovers common patterns and sources of heterogeneity in those health impacts, and enables identification of communities at highest health risk for future TCs. The model integrates (i) a causal inference component to quantify the immediate health impacts of recent historic TCs at high spatial resolution and (ii) a predictive component that captures how TC meteorological features and socioeconomic/demographic characteristics of impacted communities are associated with health impacts. We apply it to a rich data platform containing detailed historic TC exposure information and records of all-cause mortality and cardiovascular- and respiratory-related hospitalization among Medicare recipients. We report a high degree of heterogeneity in the acute health impacts of historic TCs, both within and across TCs, and, on average, substantial TC-attributable increases in respiratory hospitalizations. TC-sustained windspeeds are found to be the primary driver of mortality and respiratory risks.

Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial.

BACKGROUND: Folic acid (FA) is the oxidized form of folate found in supplements and FA-fortified foods. Most FA is reduced by dihydrofolate reductase to 5-methyltetrahydrofolate (5mTHF); the latter is the form of folate naturally found in foods. Ingestion of FA increases the plasma levels of both 5mTHF and unmetabolized FA (UMFA). Limited information is available on the downstream metabolic effects of FA supplementation, including potential effects associated with UMFA. OBJECTIVE: We aimed to assess the metabolic effects of FA-supplementation, and the associations of plasma 5mTHF and UMFA with the metabolome in FA-naïve Bangladeshi adults. METHODS: Sixty participants were selected from the Folic Acid and Creatine Trial; half received 800 µg FA/day for 12 weeks and half placebo. Plasma metabolome profiles were measured by high-resolution mass spectrometry, including 170 identified metabolites and 26,541 metabolic features. Penalized regression methods were used to assess the associations of targeted metabolites with FA-supplementation, plasma 5mTHF, and plasma UMFA. Pathway analyses were conducted using Mummichog. RESULTS: In penalized models of identified metabolites, FA-supplementation was associated with higher choline. Changes in 5mTHF concentrations were positively associated with metabolites involved in amino acid metabolism (5-hydroxyindoleacetic acid, acetylmethionine, creatinine, guanidinoacetate, hydroxyproline/n-acetylalanine) and 2 fatty acids (docosahexaenoic acid and linoleic acid). Changes in 5mTHF concentrations were negatively associated with acetylglutamate, acetyllysine, carnitine, propionyl carnitine, cinnamic acid, homogentisate, arachidonic acid, and nicotine. UMFA concentrations were associated with lower levels of arachidonic acid. Together, metabolites selected across all models were related to lipids, aromatic amino acid metabolism, and the urea cycle. Analyses of nontargeted metabolic features identified additional pathways associated with FA supplementation. CONCLUSION: In addition to the recapitulation of several expected metabolic changes associated with 5mTHF, we observed additional metabolites/pathways associated with FA-supplementation and UMFA. Further studies are needed to confirm these associations and assess their potential implications for human health. TRIAL REGISTRATION NUMBER: This trial was registered at https://clinicaltrials.gov as NCT01050556.

Daily temperature variability and mental health-related hospital visits in New York State.

BACKGROUND: Despite plausible behavioral and physiological pathways, limited evidence exists on how daily temperature variability is associated with acute mental health-related episodes. OBJECTIVES: We aimed to explore associations between daily temperature range (DTR) and mental health-related hospital visits using data of all hospital records in New York State during 1995-2014. We further examined factors that may modify these associations, including age, sex, hospital visit type and season. METHODS: Using a case-crossover design with distributed lag non-linear DTR terms (0-6 days), we estimated associations between ZIP Code-level DTR and hospital visits for mood (4.6 million hospital visits), anxiety (2.4 million), adjustment (∼368,000), and schizophrenia disorders (∼211,000), controlling for daily mean temperature, via conditional logistic regression models. We assessed potential heterogeneity by age, sex, hospital visit type (in-patient vs. out-patient), and season (summer, winter, and transition seasons). RESULTS: For all included outcomes, we observed positive associations from period minimum DTR (0.1 °C) until 25th percentile (5.2 °C) and between mean DTR (7.7 °C) and 90th percentile (12.2 °C), beyond which we observed negative associations. For mood disorders, an increase in DTR from 0.1 °C to 12.2 °C was associated with a cumulative 16.0% increase (95% confidence interval [CI]: 12.8, 19.2%) in hospital visit rates. This increase was highest during transition seasons (32.5%; 95%CI: 26.4, 39.0%) compared with summer (10.7%; 95%CI: 4.8, 16.8%) and winter (-1.6%; 95%CI: -7.6, 4.7%). For adjustment and schizophrenia disorders, the strongest associations were seen among the youngest group (0-24 years) with almost no association in the oldest group (65+ years). We observed no evidence for modification by sex and hospital visit type. DISCUSSION: Daily temperature variability was positively associated with mental health-related hospital visits within specific DTR ranges in New York State, after controlling for daily mean temperature. Given uncertainty on how climate change modifies temperature variability, additional research is crucial to comprehend the implications of these findings, particularly under different scenarios of future temperature variability.

Bias Amplification and Variance Inflation in Distributed Lag Models Using Low-Spatial-Resolution Data.

Distributed lag models (DLMs) are often used to estimate lagged associations and identify critical exposure windows. In a simulation study of prenatal nitrogen dioxide (NO2) exposure and birth weight, we demonstrate that bias amplification and variance inflation can manifest under certain combinations of DLM estimation approaches and time-trend adjustment methods when using low-spatial-resolution exposures with extended lags. Our simulations showed that when using high-spatial-resolution exposure data, any time-trend adjustment method produced low bias and nominal coverage for the distributed lag estimator. When using either low- or no-spatial-resolution exposures, bias due to time trends was amplified for all adjustment methods. Variance inflation was higher in low- or no-spatial-resolution DLMs when using a long-term spline to adjust for seasonality and long-term trends due to concurvity between a distributed lag function and secular function of time. NO2-birth weight analyses in a Massachusetts-based cohort showed that associations were negative for exposures experienced in gestational weeks 15-30 when using high-spatial-resolution DLMs; however, associations were null and positive for DLMs with low- and no-spatial-resolution exposures, respectively, which is likely due to bias amplification. DLM analyses should jointly consider the spatial resolution of exposure data and the parameterizations of the time trend adjustment and lag constraints.

Exploring Relevant Time Windows in the Association Between PM2.5 Exposure and Amyotrophic Lateral Sclerosis: A Case-Control Study in Denmark.

Studies suggest a link between particulate matter less than or equal to 2.5 µm in diameter (PM2.5) and amyotrophic lateral sclerosis (ALS), but to our knowledge critical exposure windows have not been examined. We performed a case-control study in the Danish population spanning the years 1989-2013. Cases were selected from the Danish National Patient Registry based on International Classification of Diseases codes. Five controls were randomly selected from the Danish Civil Registry and matched to a case on vital status, age, and sex. PM2.5 concentration at residential addresses was assigned using monthly predictions from a dispersion model. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounding. We evaluated exposure to averaged PM2.5 concentrations 12-24 months, 2-6 years, and 2-11 years pre-ALS diagnosis; annual lagged exposures up to 11 years prediagnosis; and cumulative associations for exposure in lags 1-5 years and 1-10 years prediagnosis, allowing for varying association estimates by year. We identified 3,983 cases and 19,915 controls. Cumulative exposure to PM2.5 in the period 2-6 years prediagnosis was associated with ALS (OR = 1.06, 95% CI: 0.99, 1.13). Exposures in the second, third, and fourth years prediagnosis were individually associated with higher odds of ALS (e.g., for lag 1, OR = 1.04, 95% CI: 1.00, 1.08). Exposure to PM2.5 within 6 years before diagnosis may represent a critical exposure window for ALS.

Cohort Network: A Knowledge Graph toward Data Dissemination and Knowledge-Driven Discovery for Cohort Studies.

Contemporary environmental health sciences draw on large-scale longitudinal studies to understand the impact of environmental exposures and behavior factors on the risk of disease and identify potential underlying mechanisms. In such studies, cohorts of individuals are assembled and followed up over time. Each cohort generates hundreds of publications, which are typically neither coherently organized nor summarized, hence limiting knowledge-driven dissemination. Hence, we propose a Cohort Network, a multilayer knowledge graph approach to extract exposures, outcomes, and their connections. We applied the Cohort Network on 121 peer-reviewed papers published over the past 10 years from the Veterans Affairs (VA) Normative Aging Study (NAS). The Cohort Network visualized connections between exposures and outcomes across different publications and identified key exposures and outcomes, such as air pollution, DNA methylation, and lung function. We demonstrated the utility of the Cohort Network for new hypothesis generation, e.g., identification of potential mediators of exposure-outcome associations. The Cohort Network can be used by investigators to summarize the cohort's research and facilitate knowledge-driven discovery and dissemination.

Unintended impacts of the Open Streets program on noise complaints in New York City.

BACKGROUND: During the COVID-19 pandemic, several cities allocated more public spaces for physical activity and recreation instead of road transport through Open Streets. This policy locally reduces traffic and provides experimental testbeds for healthier cities. However, it may also generate unintended impacts. For instance, Open Streets may impact the levels of exposure to environmental noise but there are no studies assessing these unintended impacts. OBJECTIVES: Using noise complaints from New York City (NYC) as a proxy of annoyance caused by environmental noise, we estimated associations at the census tract level between same-day proportion of Open Streets in a census tract and noise complaints in NYC. METHODS: Using data from summer 2019 (pre-implementation) and summer 2021 (post-implementation), we fit regressions to estimate the association between census tract-level proportion of Open Streets and daily noise complaints, with random effects to account for within-tract correlation and natural splines to allow non-linearity in the estimated association. We accounted for temporal trends and other potential confounders, such as population density and poverty rate. RESULTS: In adjusted analyses, daily street/sidewalk noise complaints were nonlinearly associated with an increasing proportion of Open Streets. Specifically, compared to the mean proportion of Open Streets in a census tract (0.11%), 5% of Open Streets had a 1.09 (95% CI: 0.98, 1.20) and 10% had a 1.21 (95% CI: 1.04, 1.42) times higher rate of street/sidewalk noise complaints. Our results were robust to the choice of data source for identifying Open Streets. CONCLUSION: Our findings suggest that Open Streets in NYC may be linked to an increase in street/sidewalk noise complaints. These results highlight the necessity to reinforce urban policies with a careful analysis for potential unintended impacts to optimize and maximize the benefits of these policies.

Fine particulate matter composition in American Indian vs. Non-American Indian communities.

BACKGROUND: Fine particulate matter (PM2.5) exposure is a known risk factor for numerous adverse health outcomes, with varying estimates of component-specific effects. Populations with compromised health conditions such as diabetes can be more sensitive to the health impacts of air pollution exposure. Recent trends in PM2.5 in primarily American Indian- (AI-) populated areas examined in previous work declined more gradually compared to the declines observed in the rest of the US. To further investigate components contributing to these findings, we compared trends in concentrations of six PM2.5 components in AI- vs. non-AI-populated counties over time (2000-2017) in the contiguous US. METHODS: We implemented component-specific linear mixed models to estimate differences in annual county-level concentrations of sulfate, nitrate, ammonium, organic matter, black carbon, and mineral dust from well-validated surface PM2.5 models in AI- vs. non-AI-populated counties, using a multi-criteria approach to classify counties as AI- or non-AI-populated. Models adjusted for population density and median household income. We included interaction terms with calendar year to estimate whether concentration differences in AI- vs. non-AI-populated counties varied over time. RESULTS: Our final analysis included 3108 counties, with 199 (6.4%) classified as AI-populated. On average across the study period, adjusted concentrations of all six PM2.5 components in AI-populated counties were significantly lower than in non-AI-populated counties. However, component-specific levels in AI- vs. non-AI-populated counties varied over time: sulfate and ammonium levels were significantly lower in AI- vs. non-AI-populated counties before 2011 but higher after 2011 and nitrate levels were consistently lower in AI-populated counties. CONCLUSIONS: This study indicates time trend differences of specific components by AI-populated county type. Notably, decreases in sulfate and ammonium may contribute to steeper declines in total PM2.5 in non-AI vs. AI-populated counties. These findings provide potential directives for additional monitoring and regulations of key emissions sources impacting tribal lands.

Early-Life Exposure to Green Space and Mid-Childhood Cognition in the Project Viva Cohort, Massachusetts.

The association between early-life greenness and child cognition is not well understood. Using prospective data from Project Viva (n = 857) from 1999-2010, we examined associations of early-life greenness exposure with mid-childhood cognition. We estimated residential greenness at birth, early childhood (median age 3.1 years), and mid-childhood (7.8 years) using 30-m resolution Landsat satellite imagery (normalized difference vegetation index). In early childhood and mid-childhood, we administered standardized assessments of verbal and nonverbal intelligence, visual-motor abilities, and visual memory. We used natural splines to examine associations of early life-course greenness with mid-childhood cognition, adjusting for age, sex, race, income, neighborhood socioeconomic status, maternal intelligence, and parental education. At lower levels of greenness (greenness <0.6), greenness exposure at early childhood was associated with a 0.48% increase in nonverbal intelligence and 2.64% increase in visual memory in mid-childhood. The association between early-childhood greenness and mid-childhood visual memory was observed after further adjusting for early childhood cognition and across different methodologies, while the association with nonverbal intelligence was not. No other associations between early life-course greenness and mid-childhood cognition were found. Early childhood greenness was nonlinearly associated with higher mid-childhood visual memory. Our findings highlight the importance of nonlinear associations between greenness and cognition.

Long-Term Fine Particulate Matter Concentrations and Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2: Differential Relationships by Socioeconomic Status Among Pregnant Individuals in New York City.

We aimed to determine whether long-term ambient concentrations of fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5)) were associated with increased risk of testing positive for coronavirus disease 2019 (COVID-19) among pregnant individuals who were universally screened at delivery and whether socioeconomic status (SES) modified this relationship. We used obstetrical data collected from New-York Presbyterian Hospital/Columbia University Irving Medical Center in New York, New York, between March and December 2020, including data on Medicaid use (a proxy for low SES) and COVID-19 test results. We linked estimated 2018-2019 PM2.5 concentrations (300-m resolution) with census-tract-level population density, household size, income, and mobility (as measured by mobile-device use) on the basis of residential address. Analyses included 3,318 individuals; 5% tested positive for COVID-19 at delivery, 8% tested positive during pregnancy, and 48% used Medicaid. Average long-term PM2.5 concentrations were 7.4 (standard deviation, 0.8) µg/m3. In adjusted multilevel logistic regression models, we saw no association between PM2.5 and ever testing positive for COVID-19; however, odds were elevated among those using Medicaid (per 1-µg/m3 increase, odds ratio = 1.6, 95% confidence interval: 1.0, 2.5). Further, while only 22% of those testing positive showed symptoms, 69% of symptomatic individuals used Medicaid. SES, including unmeasured occupational exposures or increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to concurrent social and environmental exposures, may explain the increased odds of testing positive for COVID-19 being confined to vulnerable pregnant individuals using Medicaid.

Smoking During Pregnancy and Risk of Attention-deficit/Hyperactivity Disorder in the Third Generation.

BACKGROUND: Animal experiments indicate that environmental factors, such as cigarette smoke, can have multigenerational effects through the germline. However, there are little data on multigenerational effects of smoking in humans. We examined the associations between grandmothers' smoking while pregnant and risk of attention-deficit/hyperactivity disorder (ADHD) in her grandchildren. METHODS: Our study population included 53,653 Nurses' Health Study II (NHS-II) participants (generation 1 [G1]), their mothers (generation 0 [G0]), and their 120,467 live-born children (generation 2 [G2]). In secondary analyses, we used data from 23,844 mothers of the nurses who were participants in the Nurses' Mothers' Cohort Study (NMCS), a substudy of NHS-II. RESULTS: The prevalence of G0 smoking during the pregnancy with the G1 nurse was 25%. ADHD was diagnosed in 9,049 (7.5%) of the grandchildren (G2). Grand-maternal smoking during pregnancy was associated with increased odds of ADHD among the grandchildren (adjusted odds ratio [aOR] = 1.2; 95% confidence interval [CI] = 1.1, 1.2), independent of G1 smoking during pregnancy. In the Nurses' Mothers' Cohort Study, odds of ADHD increased with increasing cigarettes smoked per day by the grandmother (1-14 cigarettes: aOR = 1.1; 95% CI = 1.0, 1.2; 15+: aOR = 1.2; 95% CI = 1.0, 1.3), compared with nonsmoking grandmothers. CONCLUSIONS: Grandmother smoking during pregnancy is associated with an increased risk of ADHD among the grandchildren.

A Bayesian Multi-Outcome Analysis of Fine Particulate Matter and Cardiorespiratory Hospitalizations.

BACKGROUND: Short-term fine particulate matter (PM2.5) exposure is positively associated with acute cardiovascular and respiratory events. Understanding whether this association varies across specific cardiovascular and respiratory conditions has important biologic, clinical, and public health implications. METHODS: We conducted a time-stratified case-crossover study of hospitalizations from 2000 through 2014 among United States Medicare beneficiaries aged 65+. The outcomes were hospitalizations with any of 57 cardiovascular and 32 respiratory discharge diagnoses. We estimated associations with two-day moving average PM2.5 as a piecewise linear term with a knot at PM2.5 = 25 g/m3. We used Multi-Outcome Regression with Tree-structured Shrinkage (MOReTreeS) to identify de novo groups of related diseases such that PM2.5 associations are: (1) similar within outcome groups; but (2) different between outcome groups. We adjusted for temperature, humidity, and individual-level characteristics. We introduce an R package, moretrees. RESULTS: Our dataset included 16,007,293 cardiovascular and 8,690,837 respiratory hospitalizations. Of 57 cardiovascular diseases, 51 were grouped and positively associated with PM2.5. We observed a stronger positive association for heart failure, which formed a separate group. We observed negative associations for groups containing the outcomes other aneurysm and intracranial hemorrhage. Of 32 respiratory outcomes, 31 were grouped and were positively associated with PM2.5. Influenza formed a separate group with a negative association. CONCLUSIONS: We used a new statistical approach, MOReTreeS, to uncover variation in the association between short-term PM2.5 exposure and hospitalizations for cardiovascular and respiratory causes controlling for patient characteristics, time trends, and environmental confounders.

Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. METHODS: In this population-based case-control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989-2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NO x ), carbon monoxide (CO), and fine particles (PM 2.5 ) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NO x , CO). RESULTS: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m 3 ) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = -1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NO x (SD = 20 µg/m 3 ) (-4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m 3 ) (-3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM 2.5 ) (SD = 2.37 µg/m 3 ) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. CONCLUSIONS: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.

Air Pollution in American Indian Versus Non-American Indian Communities, 2000-2018.

Objectives. To compare fine particulate matter (PM2.5) concentrations in American Indian (AI)-populated with those in non-AI-populated counties over time (2000-2018) in the contiguous United States. Methods. We used a multicriteria approach to classify counties as AI- or non--AI-populated. We ran linear mixed effects models to estimate the difference in countywide annual PM2.5 concentrations from well-validated prediction models and monitoring sites (modeled and measured PM2.5, respectively) in AI- versus non-AI-populated counties. Results. On average, adjusted modeled PM2.5 concentrations in AI-populated counties were 0.38 micrograms per cubic meter (95% confidence interval [CI] = 0.23, 0.54) lower than in non-AI-populated counties. However, this difference was not constant over time: in 2000, modeled concentrations in AI-populated counties were 1.46 micrograms per cubic meter (95% CI = 1.25, 1.68) lower, and by 2018, they were 0.66 micrograms per cubic meter (95% CI = 0.45, 0.87) higher. Over the study period, adjusted modeled PM2.5 mean concentrations decreased by 2.13 micrograms per cubic meter in AI-populated counties versus 4.26 micrograms per cubic meter in non-AI-populated counties. Results were similar for measured PM2.5. Conclusions. This study highlights disparities in PM2.5 trends between AI- and non-AI-populated counties over time, underscoring the need to strengthen air pollution regulations and prevention implementation in tribal territories and areas where AI populations live. (Am J Public Health. 2022;112(4): 615-623. https://doi.org/10.2105/AJPH.2021.306650).

The associations of prenatal exposure to dioxins and polychlorinated biphenyls with neurodevelopment at 6 Months of age: Multi-pollutant approaches.

BACKGROUND: Prenatal exposure to persistent organic pollutants, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs), and nondioxin-like PCBs (NDL-PCBs), has been hypothesized to have a detrimental impact on neurodevelopment. However, the association of prenatal exposure to a dioxin and PCB mixture with neurodevelopment remains largely inconclusive partly because these chemical levels are correlated. OBJECTIVES: We aimed to elucidate the association of in utero exposure to a mixture of dioxins and PCBs with neurodevelopment measured at 6 months of age by applying multipollutant methods. METHODS: A total of 514 pregnant women were recruited between July 2002 and October 2005 in the Sapporo cohort, Hokkaido Study on Environment and Children's Health. The concentrations of individual dioxin and PCB isomers were assessed in maternal peripheral blood during pregnancy. The mental and psychomotor development of the study participants' infants was evaluated using the Bayley Scales of Infant Development-2nd Edition (n = 259). To determine both the joint and individual associations of prenatal exposure to a dioxin and PCB mixture with infant neurodevelopment, Bayesian kernel machine regression (BKMR) and quantile-based g-computation were employed. RESULTS: Suggestive inverse associations were observed between in utero exposure to a dioxin and PCB mixture and infant psychomotor development in both the BKMR and quantile g-computation models. In contrast, we found no association of a dioxin and PCB mixture with mental development. When group-specific posterior inclusion probabilities were estimated, BKMR suggested prenatal exposure to mono-ortho PCBs as the more important contributing factors to early psychomotor development compared with the other dioxin or PCB groups. No evidence of nonlinear exposure-outcome relationships or interactions among the chemical mixtures was detected. CONCLUSIONS: Applying the two complementary statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and PCBs with infant psychomotor development.

Can weather help explain 'why now?': The potential role of hourly temperature as a stroke trigger.

BACKGROUND: While evidence suggests that daily ambient temperature exposure influences stroke risk, little is known about the potential triggering role of ultra short-term temperature. METHODS: We examined the association between hourly temperature and ischemic and hemorrhagic stroke, separately, and identified any relevant lags of exposure among adult New York State residents from 2000 to 2015. Cases were identified via ICD-9 codes from the New York Department of Health Statewide Planning and Reearch Cooperative System. We estimated ambient temperature up to 36 h prior to estimated stroke onset based on patient residential ZIP Code. We applied a time-stratified case-crossover study design; control periods were matched to case periods by year, month, day of week, and hour of day. Additionally, we assessed effect modification by leading stroke risk factors hypertension and atrial fibrillation. RESULTS: We observed 578,181 ischemic and 164,755 hemorrhagic strokes. Among ischemic and hemorrhagic strokes respectively, the mean (standard deviation; SD) patient age was 71.8 (14.6) and 66.8 (17.4) years, with 55% and 49% female. Temperature ranged from -29.5 °C to 39.2 °C, with mean (SD) 10.9 °C (10.3 °C). We found linear relationships for both stroke types. Higher temperature was associated with ischemic stroke over the 7 h following exposure; a 10 °C increase over 7 h was associated with 5.1% (95% Confidence Interval [CI]: 3.8, 6.4%) increase in hourly stroke rate. In contrast, temperature was negatively associated with hemorrhagic stroke over 5 h, with a 5-h cumulative association of -6.2% (95% CI: 8.6, -3.7%). We observed suggestive evidence of a larger association with hemorrhagic stroke among patients with hypertension and a smaller association with ischemic stroke among those with atrial fibrillation. CONCLUSION: Hourly temperature was positively associated with ischemic stroke and negatively associated with hemorrhagic stroke. Our results suggest that ultra short-term weather influences stroke risk and hypertension may confer vulnerability.

Prenatal maternal phthalate exposures and trajectories of childhood adiposity from four to twelve years.

BACKGROUND/AIM: Adiposity trajectories reflect dynamic process of growth and may predict later life health better than individual measures. Prenatal phthalate exposures may program later childhood adiposity, but findings from studies examining these associations are conflicting. We investigated associations between phthalate biomarker concentrations during pregnancy with child adiposity trajectories. METHODS: We followed 514 mother-child pairs from the Mexico City PROGRESS cohort from pregnancy through twelve years. We measured concentrations of nine phthalate biomarkers in 2nd and 3rd trimester maternal urine samples to create a pregnancy average using the geometric mean. We measured child BMI z-score, fat mass index (FMI), and waist-to-height ratio (WHtR) at three study visits between four and 12 years of age. We identified adiposity trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We estimated associations of phthalates biomarkers with class membership using multinomial logistic regression. We used quantile g-computation to estimate the potential effect of the total phthalate mixture and assessed effect modification by sex. RESULTS: We identified three trajectories of child adiposity, a "low-stable", a "low-high", and a "high-high" group. A doubling of the sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHP), was associated with 1.53 (1.08, 2.19) greater odds of being in the "high-high" trajectory in comparison to the "low-stable" group, whereas a doubling in di-isononyl phthalate metabolites (ΣDiNP) was associated with 1.43 (1.02, 2.02) greater odds of being in the "low-high" trajectory and mono (carboxy-isononyl) phthalate (MCNP) was associated with 0.66 (0.45, 97) lower odds of being in the "low-high" trajectory. No sex-specific associations or mixture associations were observed. CONCLUSIONS: Prenatal concentrations of urinary DEHP metabolites, DiNP metabolites, and MCNP, a di-isodecyl phthalate metabolite, were associated with trajectories of child adiposity. The total phthalate mixture was not associated with early life child adiposity.

Mixed metals exposure and cognitive function in Bangladeshi adolescents.

BACKGROUND: Over 57 million people in Bangladesh have been chronically exposed to arsenic-contaminated drinking water. They also face environmental exposure to elevated levels of cadmium (Cd), manganese (Mn), and lead (Pb), all of which have been previously observed in environmental and biological samples for this population. These metals have been linked to adverse neurocognitive outcomes in adults and children, though their effects on adolescents are not yet fully characterized. Additionally, previous studies have linked selenium (Se) to protective effects against the toxicity of these other metals. OBJECTIVES: To examine the associations between mixed metals exposure and cognitive function in Bangladeshi adolescents. METHODS: The Metals, Arsenic, & Nutrition in Adolescents study (MANAs) is a cross-sectional study of 572 Bangladeshi adolescents aged 14-16 years, whose parents were enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Biosamples were collected from these adolescents for measurement of whole blood metalloid/metal levels of As, Cd, Mn, Pb, and Se. Participants also completed an abbreviated version of The Cambridge Neuropsychological Test Automated Battery (CANTAB), a cognitive function test designed to measure performance across several aspects of executive function. Linear regression was used to examine associations for each metal while controlling for the other metals. Bayesian Kernel Machine Regression (BKMR) assessed the overall mixture effect in addition to confirming the effects of individual metal components observed via linear regression. RESULTS: Linear regression revealed negative associations for Spatial Working Memory and both As and Mn (As B=-2.40, Mn B=-5.31, p < 0.05). We also observed negative associations between Cd and Spatial Recognition Memory (B=-2.77, p < 0.05), and Pb and Delayed Match to Sample, a measure of visual recognition and memory (B=-3.67, p < 0.05). Finally, we saw a positive association for Se and Spatial Span Length (B=0.92, p < 0.05). BKMR results were largely consistent with the regression analysis, showing meaningful associations for individual metals and CANTAB subtests, but no overall mixture effect. Via BKMR, we observed negative associations between Pb and Delayed Match to Sample, and Cd and Spatial Recognition Memory; this analysis also showed positive associations for Se and the Planning, Reaction Time, and Spatial Span subtests. BKMR posterior inclusion probability consistently reported that Se, the only component of the mixture to show a positive association with cognition, was the most important member of the mixture. CONCLUSIONS: Overall, we found Se to be positively associated with cognition, while Mn and As were linked to poorer working memory, and Cd and Pb were associated with poorer visual recognition and memory. Our observations are consistent with previous reports on the effects of these metal exposures in adults and children. Our findings also suggest agreement between linear regression and BKMR methods for analyzing metal mixture exposures. Additional studies are needed to evaluate the impact of mixed metals exposure on adverse health and poorer cognition later in life for those exposed during adolescence. Findings also suggest that metal exposure mitigation efforts aimed at adolescents might influence lifelong cognitive outcomes in regions where environmental exposure to metals is endemic.

Association of Tropical Cyclones With County-Level Mortality in the US.

Importance: Tropical cyclones have a devastating effect on society, but a comprehensive assessment of their association with cause-specific mortality over multiple years of study is lacking. Objective: To comprehensively evaluate the association of county-level tropical cyclone exposure and death rates from various causes in the US. Design, Setting, and Participants: A retrospective observational study using a Bayesian conditional quasi-Poisson model to examine how tropical cyclones were associated with monthly death rates. Data from 33.6 million deaths in the US were collected from the National Center for Health Statistics over 31 years (1988-2018), including residents of the 1206 counties in the US that experienced at least 1 tropical cyclone during the study period. Exposures: Tropical cyclone days per county-month, defined as number of days in a month with a sustained maximal wind speed 34 knots or greater. Main Outcomes and Measures: Monthly cause-specific county-level death rates by 6 underlying causes of death: cancers, cardiovascular diseases, infectious and parasitic diseases, injuries, neuropsychiatric conditions, and respiratory diseases. The model yielded information about the association between each additional cyclone day per month and monthly county-level mortality compared with the same county-month in different years, up to 6 months after tropical cyclones, and how these estimated associations varied by age, sex, and social vulnerability. The unit of analysis was county-month. Results: There were 33 619 393 deaths in total (16 691 681 females and 16 927 712 males; 8 587 033 aged 0-64 years and 25 032 360 aged 65 years or older) from the 6 causes recorded in 1206 US counties. There was a median of 2 tropical cyclone days experienced in total in included US counties. Each additional cyclone day was associated with increased death rates in the month following the cyclone for injuries (3.7% [95% credible interval {CrI}, 2.5%-4.9%]; 2.0 [95% CrI, 1.3-2.7] additional deaths per 1 000 000 for 2018 monthly age-standardized median rate [DPM]; 54.3 to 56.3 DPM), infectious and parasitic diseases (1.8% [95% CrI, 0.1%-3.6%]; 0.2 [95% CrI, 0.0-0.4] additional DPM; 11.7 to 11.9 DPM), respiratory diseases (1.3% [95% CrI, 0.2%-2.4%]; 0.6 [95% CrI, 0.1-1.1] additional DPM; 44.9 to 45.5 DPM), cardiovascular diseases (1.2% [95% CrI, 0.6%-1.7%]; 1.5 [95% CrI, 0.8-2.2] additional DPM; 129.6 to 131.1 DPM), neuropsychiatric conditions (1.2% [95% CrI, 0.1%-2.4%]; 0.6 [95% CrI, 0.1-1.2] additional DPM; 52.1 to 52.7 DPM), with no change for cancers (-0.3% [95% CrI, -0.9% to 0.3%]; -0.3 [95% CrI, -0.9 to 0.3] additional DPM; 100.4 to 100.1 DPM). Conclusions and Relevance: Among US counties that experienced at least 1 tropical cyclone from 1988-2018, each additional cyclone day per month was associated with modestly higher death rates in the months following the cyclone for several causes of death, including injuries, infectious and parasitic diseases, cardiovascular diseases, neuropsychiatric conditions, and respiratory diseases.