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.

Association between prenatal air pollutant exposure and autism spectrum disorders in young children: a matched case-control study in Canada.

The direction and magnitude of association between maternal exposure to ambient air pollutants across gestational windows and offspring risk of autism spectrum disorders (ASD) remains unclear. We sought to evaluate the time-varying effects of prenatal air pollutant exposure on ASD. We conducted a matched case-control study of singleton term children born in Ontario, Canada from 1-Apr-2012 to 31-Dec-2016. Provincial birth registry data were linked with applied behavioural analysis services and ambient air pollutant datasets to ascertain prenatal exposure to nitrogen dioxide (NO2), ground-level ozone (O3), fine particulate matter (PM2.5), and ASD diagnoses. Covariate balance between cases and controls was established using coarsened exact matching. Conditional logistic regression was used to assess the association between prenatal air pollutant exposure and ASD. Distributed lag non-linear models (DLNM) were used to examine the effects of single-pollutant exposure by prenatal week. Sensitivity analyses were conducted to assess the impact of exposure period on the observed findings. The final sample included 1,589 ASD cases and 7,563 controls. Compared to controls, cases were more likely to be born to mothers living in urban areas, delivered by Caesarean section, and assigned male sex at birth. NO2 was a consistent and significant contributor to ASD risk after accounting for co-exposure to O3, PM2.5 and covariates. The odds ratio per interquartile range increase was 2.1 (95%CI 1.8-2.3) pre-conception, 2.2 (2.0-2.5) for the 1st trimester, 2.2 (1.9-2.5) for the 2nd trimester, and 2.1 (1.9-2.4) for the 3rd trimester. In contrast, findings for O3 and PM2.5 with ASD were inconsistent. Findings from DLNM and sensitivity analyses were similar. Exposure to NO2 before and during pregnancy was significantly associated with ASD in offspring. The relationship between prenatal O3 and PM2.5 exposure and ASD remains unclear. Further investigation into the combined effects of multi-pollutant exposure on child neurodevelopment is warranted.

Critical windows of exposure to air pollution and gestational diabetes: assessing effect modification by maternal pre-existing conditions and environmental factors.

BACKGROUND: Ambient air pollution has been associated with gestational diabetes (GD), but critical windows of exposure and whether maternal pre-existing conditions and other environmental factors modify the associations remains inconclusive. METHODS: We conducted a retrospective cohort study of all singleton live birth that occurred between April 1st 2006 and March 31st 2018 in Ontario, Canada. Ambient air pollution data (i.e., fine particulate matter with a diameter ≤ 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3)) were assigned to the study population in spatial resolution of approximately 1 km × 1 km. The Normalized Difference Vegetation Index (NDVI) and the Green View Index (GVI) were also used to characterize residential exposure to green space as well as the Active Living Environments (ALE) index to represent the active living friendliness. Multivariable Cox proportional hazards regression models were used to evaluate the associations. RESULTS: Among 1,310,807 pregnant individuals, 68,860 incident cases of GD were identified. We found the strongest associations between PM2.5 and GD in gestational weeks 7 to 18 (HR = 1.07 per IQR (2.7 µg/m3); 95% CI: 1.02 - 1.11)). For O3, we found two sensitive windows of exposure, with increased risk in the preconception period (HR = 1.03 per IQR increase (7.0 ppb) (95% CI: 1.01 - 1.06)) as well as gestational weeks 9 to 28 (HR 1.08 per IQR (95% CI: 1.04 -1.12)). We found that women with asthma were more at risk of GD when exposed to increasing levels of O3 (p- value for effect modification = 0.04). Exposure to air pollutants explained 20.1%, 1.4% and 4.6% of the associations between GVI, NDVI and ALE, respectively. CONCLUSION: An increase of PM2.5 exposure in early pregnancy and of O3 exposure during late first trimester and over the second trimester of pregnancy were associated with gestational diabetes whereas exposure to green space may confer a protective effect.

Residential proximity to greenness and adverse birth outcomes in urban areas: Findings from a national Canadian population-based study.

BACKGROUND: Over the last decade, several studies have reported that residential proximity to vegetation, or 'greenness', is associated with improved birth outcomes, including for term birth weight (TBW), preterm birth (PTB), and small for gestational age (SGA). However, there remain several uncertainties about these possible benefits including the role of air pollution, and the extent to they are influenced socioeconomic status. METHODS: We addressed these gaps using a national population-based study of 2.2 million singleton live births in Canadian metropolitan areas between 1999 and 2008. Exposures to greenness, fine particulate matter (PM2.5), and nitrogen dioxide (NO2) were assigned to infants using the postal code of their mother's residence at the time of birth. The Normalized Difference Vegetation Index (NDVI) was used to characterize greenness, while estimates of ambient PM2.5 and NO2 were estimated using remote sensing, and a national land-use regression surface, respectively. Multivariable regression analysis was performed to describe associations between residential greenness and the birth outcomes. Stratified analyses explored whether these associations were modified by neighbourhood measures of socioeconomic status. RESULTS: Mothers who lived in greener areas had a lower risk of low TBW, PTB, and SGA babies. These associations persisted after adjustment for ambient NO2 and PM2.5. Specifically, in fully adjusted models, an interquartile range (IQR = 0.16) increase in the NDVI within a residential buffer of 250 m yielded odds ratios of 0.93 (95% confidence interval (CI): 0.92, 0.94), 0.94 (95% CI: 0.92, 0.95), and 0.94 (95% CI: 0.93, 0.95) for the outcomes of PTB, low TBW, and SGA, respectively. Similarly, an IQR increase in greenness was associated with a 16.3 g (95% CI: 15.3, 17.4) increase in TBW. We found inverse associations between greenness and the occurrence of adverse birth outcomes regardless of the socioeconomic status of the neighbourhood. INTERPRETATION: Our findings support the hypothesis that residential greenness contributes to healthier pregnancies, that these associations are independent from exposure to air pollution. , and that proximity to greenness benefits all mothers regardless of socioeconomic status.

Within-City Variation in Reactive Oxygen Species from Fine Particle Air Pollution and COVID-19.

Rationale: Evidence linking outdoor air pollution with coronavirus disease (COVID-19) incidence and mortality is largely based on ecological comparisons between regions that may differ in factors such as access to testing and control measures that may not be independent of air pollution concentrations. Moreover, studies have yet to focus on key mechanisms of air pollution toxicity such as oxidative stress. Objectives: To conduct a within-city analysis of spatial variations in COVID-19 incidence and the estimated generation of reactive oxygen species (ROS) in lung lining fluid attributable to fine particulate matter (particulate matter with an aerodynamic diameter ⩽2.5 µm [PM2.5]). Methods: Sporadic and outbreak-related COVID-19 case counts, testing data, population data, and sociodemographic data for 140 neighborhoods were obtained from the City of Toronto. ROS estimates were based on a mathematical model of ROS generation in lung lining fluid in response to iron and copper in PM2.5. Spatial variations in long-term average ROS were predicted using a land-use regression model derived from measurements of iron and copper in PM2.5. Data were analyzed using negative binomial regression models adjusting for covariates identified using a directed acyclic graph and accounting for spatial autocorrelation. Measurements and Main Results: A significant positive association was observed between neighborhood-level ROS and COVID-19 incidence (incidence rate ratio = 1.07; 95% confidence interval, 1.01-1.15 per interquartile range ROS). Effect modification by neighborhood-level measures of racialized group membership and socioeconomic status was also identified. Conclusions: Examination of neighborhood characteristics associated with COVID-19 incidence can identify inequalities and generate hypotheses for future studies.

Associations between air pollution and cardio-respiratory physiological measures in older adults exercising outdoors.

We examined whether exercising indoors vs. outdoors reduced the cardio-respiratory effects of outdoor air pollution. Adults ≥55 were randomly assigned to exercise indoors when the Air Quality Health Index was ≥5 and outdoors on other days (intervention group, n = 37), or outdoors everyday (control group, n = 35). Both groups completed cardio-respiratory measurements before and after exercise for up to 10 weeks. Data were analyzed using linear mixed effect regression models. In the control group, an interquartile range increase in fine particulate matter (PM2.5) was associated with increases of 1.4% in heart rate (standard error (SE) = 0.7%) and 5.6% (SE = 2.6%) in malondialdehyde, and decreases of 5.6% (SE = 2.5%) to 16.5% (SE = 7.5%) in heart rate variability measures. While the hypothesized benefit of indoor vs. outdoor exercise could not be demonstrated due to an insufficient number of intervention days (n = 2), the study provides evidence of short-term effects of air pollution in older adults. ISRCTN #26552763.

Space-time hot spots of critically ill small for gestational age newborns and industrial air pollutants in major metropolitan areas of Canada.

We assessed the association of spatiotemporal hot spots of critically ill small for gestational age (ciSGA) newborns and industrial air emissions. Using neonatal admission data from the Canadian Neonatal Network between 2006 and 2010 (n = 32,836 infants), we aggregated maternal residential postal codes from nineteen census metropolitan areas (CMA) into space-time cubes and applied emerging hot spot analyses. Using National Pollutant Release Inventory data (n = 161 chemicals) and Environment Canada weather station data (n = 19 sites), we estimated monthly wind-dispersion of air emissions and calculated hot spots. We associated the patterns using logistic regression, with covariates for low socioeconomic status, NO2 pollution, and number of infants. A total of 5465 infants were identified as ciSGA and the larger CMAs had more and larger hot spots (i.e. accumulation of events in space and time). Seventy-eight industrial chemical hot spots were associated with ciSGA hot spots. The highest number of positive associations were for 28 different pollutants, which differed by CMA. Twenty-one were known or suspected developmental toxicants, such as particulate matter, carbon monoxide, heavy metals, and volatile organic compounds. Associations with hot spots of industrial chemical emissions were geographically specific and may help explain the space-time trends of ciSGA.

An ecological analysis of long-term exposure to PM2.5 and incidence of COVID-19 in Canadian health regions.

BACKGROUND: Ambient fine particulate matter (PM2.5) is associated with a wide range of acute and chronic health effects, including increased risk of respiratory infection. However, evidence specifically related to novel coronavirus disease (COVID-19) is limited. METHODS: COVID-19 case counts for 111 Canadian health regions were obtained from the COVID-19 Canada Open Data portal. Annual PM2.5 data for 2000-2016 were estimated from a national exposure surface based on remote sensing, chemical transport modelling and ground observations, and minimum and maximum temperature data for 2000-2015 were based on a national interpolated surface derived from thin-plate smoothing splines. Population counts and sociodemographic data by health region were obtained from the 2016 census, and health data (self-rated health and prevalence of smoking, obesity, and selected chronic diseases) by health region, were obtained from the Canadian Community Health Survey. Data on total number of COVID-19 tests and changes in mobility comparing post-vs. pre-introduction of social distancing measures were available by province. Data were analyzed using negative binomial regression models. RESULTS: After controlling for province, temperature, demographic and health characteristics and days since peak incidence by health region, long-term PM2.5 exposure exhibited a positive association with COVID-19 incidence (incidence rate ratio 1.07, 95% confidence interval 0.97-1.18 per µg/m3). This association was larger in magnitude and statistically significant in analyses excluding provinces that reported cases only for aggregated health regions, excluding health regions with less than median population density, and restricted to the most highly affected provinces (Quebec and Ontario). CONCLUSIONS: We observed a positive association between COVID-19 incidence and long-term PM2.5 exposure in Canadian health regions. The association was larger in magnitude and statistically significant in more highly affected health regions and those with potentially less exposure measurement error. While our results generate hypotheses for further testing, they should be interpreted with caution and require further examination using study designs less prone to bias.

Ambient air pollution and incidence of early-onset paediatric type 1 diabetes: A retrospective population-based cohort study.

BACKGROUND: Studies have reported increasing incidence rates of paediatric diabetes, especially among those aged 0-5 years. Epidemiological evidence linking ambient air pollution to paediatric diabetes remains mixed. OBJECTIVE: This study investigated the association between maternal and early-life exposures to common air pollutants (NO2, PM2.5, O3, and oxidant capacity [Ox; the redox-weighted average of O3 and NO2]) and the incidence of paediatric diabetes in children up to 6 years of age. METHODS: All registered singleton births in Ontario, Ca nada occurring between April 1st, 2006 and March 31st, 2012 were included through linkage from health administrative data. Monthly exposures to NO2, PM2.5, O3, and Ox were estimated across trimesters, the entire pregnancy period and during childhood. Random effects Cox proportional hazards models were used to assess the relationships with paediatric diabetes incidence while controlling for important covariates. We also modelled the shape of concentration-response (CR) relationships. RESULTS: There were 1094 children out of a cohort of 754,698 diagnosed with diabetes before the age of six. O3 exposures during the first trimester of pregnancy were associated with paediatric diabetes incidence (hazard ratio (HR) per interquartile (IQR) increase = 2.00, 95% CI: 1.04-3.86). The CR relationship between O3 during the first trimester and paediatric diabetes incidence appeared to have a risk threshold, in which there was little-to-no risk below 25 ppb of O3, while above this level risk increased sigmoidally. No other associations were observed. CONCLUSION: O3 exposures during a critical period of development were associated with an increased risk of paediatric diabetes incidence.

Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

BACKGROUND: Nitrogen dioxide (NO2) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052-1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016-1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant. CONCLUSIONS: We concluded that there is a likely causal relationship between short term NO2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.

Correction to: Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

An amendment to this paper has been published and can be accessed via the original article.

Spatiotemporal Variations in Ambient Ultrafine Particles and the Incidence of Childhood Asthma.

Rationale: Little is known regarding the impact of ambient ultrafine particles (UFPs; <0.1 µm) on childhood asthma development. Objectives: To examine the association between prenatal and early postnatal life exposure to UFPs and development of childhood asthma. Methods: A total of 160,641 singleton live births occurring in the City of Toronto, Canada between April 1, 2006, and March 31, 2012, were identified from a birth registry. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using random effects Cox proportional hazards models, adjusting for personal- and neighborhood-level covariates. We investigated both single-pollutant and multipollutant models accounting for coexposures to particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) and NO2. Measurements and Main Results: We identified 27,062 children with incident asthma diagnosis during the follow-up. In adjusted models, second-trimester exposure to UFPs (hazard ratio per interquartile range increase, 1.09; 95% confidence interval, 1.06-1.12) was associated with asthma incidence. In models additionally adjusted for PM2.5 and nitrogen dioxide, UFPs exposure during the second trimester of pregnancy remained positively associated with childhood asthma incidence (hazard ratio per interquartile range increase, 1.05; 95% confidence interval, 1.01-1.09). Conclusions: This is the first study to evaluate the association between perinatal exposure to UFPs and the incidence of childhood asthma. Exposure to UFPs during a critical period of lung development was linked to the onset of asthma in children, independent of PM2.5 and NO2.

Using maps to communicate environmental exposures and health risks: Review and best-practice recommendations.

BACKGROUND: Graphical materials can be effective communication tools, and maps in particular are a potentially powerful means of conveying spatial information. Previous reviews have provided insights on the application of cartographic best practices, pitfalls to avoid, and considerations related to risk perception and communication, but none has reviewed primary studies of the effectiveness or utility of maps to users, nor have they addressed the issue from the perspective of health literacy, environmental health literacy, or public health ethics. OBJECTIVES: To systematically identify and review the literature pertaining to evaluation of maps in general, or specific map features, as environmental exposure and health risk communication tools; to formulate best-practice recommendations; and to identify future research priorities. METHODS: A health science librarian searched the literature for commentaries, reviews, and primary studies. Titles, abstracts, and full-text papers were screened for inclusion, and details of methods and results were extracted from 4 reviews and commentaries and 18 primary studies. This was supplemented by one additional review and 13 additional primary studies pertaining to use of maps for communication about wildfires and floods. One additional paper was identified by reviewing reference lists of all relevant papers. RESULTS: and Discussion: While there are significant gaps in the evidence, we formulated best practice recommendations highlighting the perspectives of health literacy and environmental health literacy. Key recommendations include: understanding the map developer's societal role and mental model underlying map design; defining, understanding and iteratively engaging with map users; informing map design using key theoretical constructs; accounting for factors affecting risk perception; adhering to risk communication principles and cartographic best practices; and considering environmental justice and public health ethics implications. Recommendations for future research are also provided.

Air pollution in the week prior to delivery and preterm birth in 24 Canadian cities: a time to event analysis.

BACKGROUND: Numerous studies have examined the association between air pollution and preterm birth (< 37 weeks gestation) but findings have been inconsistent. These associations may be more difficult to detect than associations with other adverse birth outcomes because of the different duration of exposure in preterm vs. term births, and the existence of seasonal cycles in incidence of preterm birth. METHODS: We analyzed data pertaining to 1,001,700 singleton births occurring between 1999 and 2008 in 24 Canadian cities where daily air pollution data were available from government monitoring sites. In the first stage, data were analyzed in each city employing Cox proportional hazards models using gestational age in days as the time scale, obtaining city-specific hazard ratios (HRs) with their 95% confidence intervals (CIs) expressed per interquartile range (IQR) of each air pollutant. Effects were examined using distributed lag functions for lags of 0-6 days prior to delivery, as well as cumulative lags from two to six days. We accounted for the potential nonlinear effect of daily mean ambient temperature using a cubic B-spline with three internal knots. In the second stage, we pooled the estimated city-specific hazard ratios using a random effects model. RESULTS: Pooled estimates across 24 cities indicated that an IQR increase in ozone (O3, 13.3 ppb) 0-3 days prior to delivery was associated with a hazard ratio of 1.036 (95% CI 1.005, 1.067) for preterm birth, adjusting for infant sex, maternal age, marital status and country of birth, neighbourhood socioeconomic status (SES) and visible minority, temperature, year and season of birth, and a natural spline function of day of year. There was some evidence of effect modification by gestational age and season. Associations with carbon monoxide, nitrogen dioxide, particulate matter, and sulphur dioxide were inconsistent. CONCLUSIONS: We observed associations between daily O3 in the week before delivery and preterm birth in an analysis of approximately 1 million births in 24 Canadian cities between 1999 and 2008. Our analysis is one of a limited number which have examined these short term associations employing Cox proportional hazards models to account for the different exposure durations of preterm vs. term births.

Effect modification of perinatal exposure to air pollution and childhood asthma incidence.

Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence, however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma.761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using Cox regression models.110,981 children with asthma were identified. In models adjusted for postnatal exposures, second trimester exposures to particulate matter with a diameter ≤2.5 µm (PM2.5) (Hazard Ratio (HR) per interquartile (IQR) increase=1.07, 95% CI: 1.06-1.09) and nitrogen dioxide (NO2) (HR per IQR increase=1.06, 95% CI: 1.03-1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, those who smoked during pregnancy, boys, those born preterm, of low birth weight and among those born to mothers living in urban areas during pregnancy.Prenatal exposure to air pollution may have a differential impact on the risk of asthma development according to maternal and infant characteristics.

Maternal Exposure to Aeroallergens and the Risk of Early Delivery.

BACKGROUND: Daily changes in aeroallergens during pregnancy could trigger early labor, but few investigations have evaluated this issue. This study aimed to investigate the association between exposure to aeroallergens during the week preceding birth and the risk of early delivery among preterm and term pregnancies. METHODS: We identified data on 225,234 singleton births that occurred in six large cities in the province of Ontario, Canada, from 2004 to 2011 (April to October) from a birth registry. We obtained daily counts of pollen grains and fungal spores from fixed-site monitoring stations in each city and assigned them to pregnancy period of each birth. Associations between exposure to aeroallergens in the preceding week and risk of delivery among preterm (<37 gestational weeks), early-term (37-38 weeks), and full-term (≥39 weeks) pregnancies were evaluated with Cox regression models, adjusting for maternal characteristics, meteorologic parameters, and air pollution concentrations, and pooled across the six cities. RESULTS: The risk of delivery increased by 3% per interquartile range width (IQRw = 22.1 grains/m) increase in weed pollen the day before birth among early-term (hazard ratio [HR] = 1.03; 95% confidence interval [CI]: 1.01, 1.05) and full-term pregnancies (HR = 1.03; 95% CI: 1.01, 1.04). Exposure to fungal spores cumulated over 0 to 2 lagged days was associated with increased risk of delivery among full-term pregnancies only (HR = 1.07; 95% CI: 1.01, 1.12). We observed no associations among preterm deliveries. CONCLUSIONS: Increasing concentrations of ambient weed pollen and fungal spores may be associated with earlier delivery among term births.