Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Multi-pollutant case-crossover models of all-cause and cause-specific mortality and hospital admissions by age group in 47 Canadian cities.

Most of the existing epidemiological studies have investigated adverse health effects of multiple air pollutants for a limited number of cities, thus the evidence of the health impacts is limited and it is challenging to compare these results because of different modeling approaches and potential publication bias. In this paper, we expand the number of Canadian cities, with the use of the most recent available health data. A multi-pollutant model in a case-crossover design is used to investigate the short-term impacts of air pollution on various health outcomes in 47 Canadian main cities, comparing three age groups (all-age, senior (age 66+), non-senior). The main findings are that a 14 ppb increase of O3 was associated with a 0.17%-2.78% (0.62%-1.46%) increase in the odds of all-age respiratory mortality (hospitalization). A 12.8 ppb increase of NO2 was associated with a 0.57%-1.47% (0.68%-1.86%) increase in the odds of all-age (non-senior) respiratory hospitalization. A 7.6 µgm-3 increase of PM2.5 was associated with a 0.19%-0.69% (0.33%-1.1%) increase in the odds of all-age (non-senior) respiratory hospitalization.

Circulatory health risks from additive multi-pollutant models: short-term exposure to three common air pollutants in Canada.

Numerous studies have reported adverse health effects of ambient air pollution on circulatory health outcomes mainly based on single-pollutant models. However, limited studies have focused on adjusted effect of multi-pollutant exposures on public health. This study aimed to examine short-term effects of three common air pollutants-ground-level ozone (ozone), nitrogen dioxide (NO2), and fine particulate matter (PM2.5)-through multi-pollutant models for mixed effect of adjustment. Daily data (circulatory hospitalization and mortality) and hourly data (air pollutants and temperature) were collected for 24 Canadian cities for 2001-2012. We applied generalized additive over-dispersion Poisson regression models with 1, 2, or 3 pollutants for city-specific risks, and Bayesian hierarchical models for national risks. This study found little mixed effect of adjustment through multi-pollutant models (ozone and/or NO2 and/or PM2.5) for circulatory hospitalization or mortality in Canada for 2001-2012, indicating that the 1-pollutant model did not result in considerable under- or over-estimates. It seemed weak-to-moderate correlations among air pollutants did not change the significant effect of one air pollutant after accounting for others. Inconsistent findings between other previous studies and this study indicate the need of comparable study design for multi-pollutant effect analysis.

Critical Time Windows for Air Pollution Exposure and Birth Weight in a Multicity Canadian Pregnancy Cohort.

BACKGROUND: Maternal prenatal exposure to air pollution has been associated with adverse birth outcomes. However, previous studies focused on a priori time intervals such as trimesters reported inconsistent associations. OBJECTIVES: We investigated time-varying vulnerability of birth weight to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using flexible time intervals. METHODS: We analyzed 1,300 live, full-term births from Maternal-Infant Research on Environmental Chemicals, a Canadian prospective pregnancy cohort spanning 10 cities (2008-2011). Daily PM2.5 and NO2 concentrations were estimated from ground-level monitoring, satellite models, and land-use regression, and assigned to participants from pre-pregnancy through delivery. We developed a flexible two-stage modeling method-using a Bayesian Metropolis-Hastings algorithm and empirical density threshold-to identify time-dependent vulnerability to air pollution without specifying exposure periods a priori. This approach identified critical windows with varying lengths (2-363 days) and critical windows that fell within, or straddled, predetermined time periods (i.e., trimesters). We adjusted the models for detailed infant and maternal covariates. RESULTS: Critical windows associated with reduced birth weight were identified during mid- to late-pregnancy for both PM2.5 and NO2: -6 g (95% credible interval: -11, -1 g) and -5 g (-10, -0.1 g) per µg/m3 PM2.5 during gestational days 91-139 and 249-272, respectively; and -3 g (-5, -1 g) per ppb NO2 during days 55-145. DISCUSSION: We used a novel, flexible selection method to identify critical windows when maternal exposures to air pollution were associated with decrements in birth weight. Our results suggest that air pollution impacts on fetal development may not be adequately captured by trimester-based analyses.

Pollutant-sex specific differences in respiratory hospitalization and mortality risk attributable to short-term exposure to ambient air pollution.

BACKGROUND: Many studies have reported associations of individual pollutants with respiratory hospitalization and mortality based on different populations, which makes it difficult to directly compare adverse health effects among multiple air pollutants. OBJECTIVES: The study goal is to compare acute respiratory-related hospitalization and mortality associated with short-term exposure to three ambient air pollutants and analyze differences in health risks by season, age and sex. METHODS: Hourly measurements of air pollutants (ozone, NO2, PM2.5) and temperature were collected from ground-monitors for 24 cities along with daily hospitalization (1996-2012) and mortality (1984-2012) data. National associations between air pollutant and health outcome were estimated for season (warm, cold vs. year-round), age (base ≥ 1, seniors > 65), and sex (females ≥ 1 and males ≥ 1) using Bayesian hierarchical models. RESULTS: Overall, the three air pollutants were significantly associated with acute respiratory health outcomes at different lag-days. For respiratory hospitalization, the increased risks in percent changes with 95% posterior intervals for a 10-unit increase in each pollutant were: ozone (lag1, 0.7% (0.4, 0.9)), NO2 (lag0, 0.7% (0.1, 1.4)), and PM2.5 (lag1, 1.3% (0.7, 1.9)). For respiratory mortality: ozone (lag2, 1.2% (0.4, 1.9)), NO2 (lag1, 2.1% (0.6, 3.5)), and PM2.5 (lag1, 0.6% (-1.0, 2.2)). While some differences in risk were observed by season and age group, sex-specific differences were more pronounced. Compared with males, females had a higher respiratory mortality risk (1.8% (0.6, 2.9) vs 0.5% (-0.3, 1.3)) from ozone, a higher respiratory hospitalization risk (0.9% (0.0, 1.8) vs 0.6% (-0.3, 1.4)) but lower mortality risk (1.4% (-1.0, 3.7) vs 2.2% (0.4, 4.0)) from NO2, and a lower hospitalization risk (0.7% (-0.2, 1.7) vs 1.8% (1.0, 2.6)) from PM2.5. CONCLUSION: This study reports significant health effects of short-term exposure to three ambient air pollutants on respiratory hospitalization (ozone≈NO2 < PM2.5 per-10 unit; ozone>NO2 ≈ PM2.5 per-IQR) and mortality (ozone≈NO2 > PM2.5) in Canada. Pollutant-sex-specific differences were found, but inconclusive due to limited biological and physiological explanations. Further studies are warranted to understand the pollutant-sex specific differences.

Comparison of hospitalization and mortality associated with short-term exposure to ambient ozone and PM2.5 in Canada.

BACKGROUND: Hospitalization and mortality (H-M) have been linked to air pollution separately. However, previous studies have not adequately compared whether air pollution is a stronger risk factor for hospitalization or mortality. This study aimed to investigate differences in H-M risk from short-term ozone and PM2.5 exposures, and determine whether differences are modified by season, age, and sex. METHODS: Daily ozone, PM2.5, temperature, and all-cause H-M counts (ICD-10, A00-R99) were collected for 22-24 Canadian cities for up to 29 years. Generalized additive Poisson models were employed to estimate associations between each pollutant and health outcome, which were compared across season (warm, cold, or year-round), age (all ages or seniors > 65), and sex. RESULTS: Overall, ozone and PM2.5 showed higher season-specific risk of mortality than hospitalization: warm-season ozone: 0.54% (95% credible interval, 0.20, 0.85) vs. 0.14% (0.02, 0.27) per 10 ppb; and year-round PM2.5: 0.90% (0.33, 1.41) vs. 0.29% (0.03, 0.56) per 10 µg/m3. While age showed little H-M difference, sex appeared to be a modifier of H-M risk. While females had higher mortality risk, males had higher hospitalization risk: for females, ozone 0.87% (0.36, 1.35) vs. -0.03% (-0.18, 0.11) and PM2.5 1.19% (0.40, 1.90) vs. 0.19% (-0.10, 0.47); and for males ozone 0.20% (-0.28, 0.65) vs. 0.35% (0.18, 0.51). CONCLUSION: This study found H-M differences attributable to ozone and PM2.5, suggesting that both are stronger risk factors for mortality than hospitalization. In addition, there were clear H-M differences by sex: specifically, females showed higher mortality risk and males showed higher hospitalization risk.

Temporal trends in associations between ozone and circulatory mortality in age and sex in Canada during 1984-2012.

BACKGROUND: Considerable research has been conducted on the association between ground-level ozone (ozone) and various causes of mortality, but the relationships by age and sex (biological) have been inconsistent, and temporal trends remain unexplored. OBJECTIVES: The study goals are to investigate the adverse health effects of short-term exposure to ozone on circulatory mortality by age and sex, and to examine trends in annual health effects. METHODS: Daily ozone, temperature, and circulatory mortality counts (ICD I00-I99) were collected for 24 urban cities for 29 years (1984-2012). Associations between ozone and circulatory mortality were estimated using generalized additive Poisson models for season (warm vs. cold), age [base (≥1) vs. seniors (>65)], and sex, accounting for confounders (calendar-time, temperature, day of the week). City-specific estimates were pooled to represent national associations through Bayesian hierarchical models. RESULTS: While the cold season returned insignificant estimates, the warm season showed statistically significant associations: a 10 ppb increase in ozone was associated with 0.7% increase in circulatory mortality with a 95% posterior interval of 0.2%, 1.1%. One-day lagged ozone in the warm season showed little age differences [0.7% (0.23%, 1.12%) vs. 0.8% (0.22%, 1.27%)], but visible sex differences: females were at a higher circulatory mortality risk than males [1.1% (0.31%, 1.71%) vs. 0.3% (-0.46%, 0.98%)]. Annual estimates suggest overall up-down temporal changes; a slightly increasing trend until 2002-2004, and a generally decreasing trend thereafter. CONCLUSION: This study found noticeable sex-related differences in circulatory mortality attributable to short-term exposure to ozone. Further research is warranted to understand whether sex alone, or unknown interactions with other factors derived the differences, and to clarify the specific biological mechanisms underlying differences in risk estimates between females and males.

The Oakville Oil Refinery Closure and Its Influence on Local Hospitalizations: A Natural Experiment on Sulfur Dioxide.

Background: An oil refinery in Oakville, Canada, closed over 2004⁻2005, providing an opportunity for a natural experiment to examine the effects on oil refinery-related air pollution and residents' health. Methods: Environmental and health data were collected for the 16 years around the refinery closure. Toronto (2.5 million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were used as control and reference populations, respectively, for Oakville (160,000 persons). We compared sulfur dioxide and age- and season-standardized hospitalizations, considering potential factors such as changes in demographics, socio-economics, drug prescriptions, and environmental variables. Results: The closure of the refinery eliminated 6000 tons/year of SO2 emissions, with an observed reduction of 20% in wind direction-adjusted ambient concentrations in Oakville. After accounting for trends, a decrease in cold-season peak-centered respiratory hospitalizations was observed for Oakville (reduction of 2.2 cases/1000 persons per year, p = 0.0006 ) but not in Toronto (p = 0.856) and the GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post closure appeared to have no observed link to known confounders or effect modifiers. Conclusion: The refinery closure allowed an assessment of the change in community health. This natural experiment provides evidence that a reduction in emissions was associated with improvements in population health. This study design addresses the impact of a removed source of air pollution.

Air Health Trend Indicator: Association between Short-Term Exposure to Ground Ozone and Circulatory Hospitalizations in Canada for 17 Years, 1996⁻2012.

The Air Health Trend Indicator is designed to estimate the public health risk related to short-term exposure to air pollution and to detect trends in the annual health risks. Daily ozone, circulatory hospitalizations and weather data for 24 cities (about 54% of Canadians) for 17 years (1996⁻2012) were used. This study examined three circulatory causes: ischemic heart disease (IHD, 40% of cases), other heart disease (OHD, 31%) and cerebrovascular disease (CEV, 14%). A Bayesian hierarchical model using a 7-year estimator was employed to find trends in the annual national associations by season, lag of effect, sex and age group (≤65 vs. >65). Warm season 1-day lagged ozone returned higher national risk per 10 ppb: 0.4% (95% credible interval, -0.3⁻1.1%) for IHD, 0.4% (-0.2⁻1.0%) for OHD, and 0.2% (-0.8⁻1.2%) for CEV. Overall mixed trends in annual associations were observed for IHD and CEV, but a decreasing trend for OHD. While little age effect was identified, some sex-specific difference was detected, with males seemingly more vulnerable to ozone for CEV, although this finding needs further investigation. The study findings could reduce a knowledge gap by identifying trends in risk over time as well as sub-populations susceptible to ozone by age and sex.

Meta-Analysis Methods to Estimate the Shape and Uncertainty in the Association Between Long-Term Exposure to Ambient Fine Particulate Matter and Cause-Specific Mortality Over the Global Concentration Range.

Estimates of excess mortality associated with exposure to ambient concentrations of fine particulate matter have been obtained from either a single cohort study or pooling information from a small number of studies. However, standard frequentist methods of pooling are known to underestimate statistical uncertainty in the true risk distribution when the number of studies pooled is small. Alternatively, Bayesian pooling methods using noninformative priors yield unrealistically large amounts of uncertainty in this case. We present a new hybrid frequentist-bayesian framework for meta-analysis that incorporates features of both frequentist and Bayesian approaches, yielding estimated uncertainty distributions that are more useful for burden estimation. We also present an example of mortality risk due to long-term exposure to ambient fine particulate matter obtained from a small number of cohort studies conducted in the United States and Europe. We compare our new risk uncertainty distribution to that obtained by the integrated exposure-response (IER) model used in the Global Burden of Disease 2010 project for which risk was modeled over the entire global concentration range. We suggest a method to incorporate our new risk uncertainty distribution based on the relatively low concentrations observed in the United States and western Europe into the IER model, thus extending risk estimation to the global concentration range.

Tracking national and regional spatial-temporal mortality risk associated with NO2 concentrations in Canada: a Bayesian hierarchical two-level model.

The association between daily variations in urban air quality and mortality has been well documented using time series statistical methods. This approach assumes a constant association over time. We develop a space-time dynamic model that relaxes this assumption, thus more directly examining the hypothesis that improvements in air quality translate into improvements in public health. We postulate a Bayesian hierarchical two-level model to estimate annual mortality risks at regional and national levels and to track both risk and heterogeneity of risk within and between regions over time. We illustrate our methods using daily nitrogen dioxide concentrations (NO2) and nonaccidental mortality data collected for 1984-2004 in 24 Canadian cities. Estimates of risk and heterogeneity are compared by cause of mortality (cardio-pulmonary [CP] versus non-CP) and season, respectively. Over the entire period, the NO2 risk for CP mortality was slightly lower but with a narrower credible interval than that for non-CP mortality, mainly due to an unusually low risk for a single year (1998). Warm season NO2 risk was higher than cold season risk for both CP and non-CP mortality. For 21 years overall there were no significant differences detected among the four regional NO2 risks. We found overall that there was no strong evidence for time trends in NO2 risk at national or regional levels. However, an increasing linear time trend in the annual between-region heterogeneities was detected, which suggests the differences in risk among the four regions are getting larger, and further studies are necessary to understand the increasing heterogeneity.

A temporal, multicity model to estimate the effects of short-term exposure to ambient air pollution on health.

BACKGROUND: Countries worldwide are expending significant resources to improve air quality partly to improve the health of their citizens. Are these societal expenditures improving public health? OBJECTIVES: We consider these issues by tracking the risk of death associated with outdoor air pollution over both space and time in Canadian cities. MATERIALS AND METHODS: We propose two multi-year estimators that use current plus several previous years of data to estimate current year risk. The estimators are derived from sequential time series analyses using moving time windows. To evaluate the statistical properties of the proposed methods, a simulation study with three scenarios of changing risk was conducted based on 12 Canadian cities from 1981 to 2000. Then an optimal estimator was applied to 24 of Canada's largest cities over the 17-year period from 1984 to 2000. RESULTS: The annual average daily concentrations of ozone appeared to be increasing over the time period, whereas those of nitrogen dioxide were decreasing. However, the proposed method returns different time trends in public health risks. Evidence for some monotonic increasing trends in the annual risks is weak for O(3) (p = 0.3870) but somewhat stronger for NO(2) (p = 0.1082). In particular, an increasing time trend becomes apparent when excluding year 1998, which reveals lower risk than proximal years, even though concentrations of NO(2) were decreasing. The simulation results validate our two proposed methods, producing estimates close to the preassigned values. CONCLUSIONS: Despite decreasing ambient concentrations, public health risks related to NO(2) appear to be increasing. Further investigations are necessary to understand why the concentrations and adverse effects of NO(2) show opposite time trends.

A new multipollutant, no-threshold air quality health index based on short-term associations observed in daily time-series analyses.

Air quality indices currently in use have been criticized because they do not capture additive effects of multiple pollutants, or reflect the apparent no-threshold concentration-response relationship between air pollution and health. We propose a new air quality health index (AQHI), constructed as the sum of excess mortality risk associated with individual pollutants from a time-series analysis of air pollution and mortality in Canadian cities, adjusted to a 0-10 scale, and calculated hourly on the basis of trailing 3-hr average pollutant concentrations. Extensive sensitivity analyses were conducted using alternative combinations of pollutants from single and multipollutant models. All formulations considered produced frequency distributions of the daily maximum AQHI that were right-skewed, with modal values of 3 or 4, and less than 10% of values at 7 or above on the 10-point scale. In the absence of a gold standard and given the uncertainty in how to best reflect the mix of pollutants, we recommend a formulation based on associations of nitrogen dioxide, ozone, and particulate matter of median aerodynamic diameter less than 2.5 microm with mortality from single-pollutant models. Further sensitivity analyses revealed good agreement of this formulation with others based on alternative sources of coefficients drawn from published studies of mortality and morbidity. These analyses provide evidence that the AQHI represents a valid approach to formulating an index with the objective of allowing people to judge the relative probability of experiencing adverse health effects from day to day. Together with health messages and a graphic display, the AQHI scale appears promising as an air quality risk communication tool.