Prenatal particulate matter exposure is linked with neurobehavioural development in early life.

BACKGROUND: Early life exposure to ambient particulate matter (PM) may negatively affect neurobehavioral development in children, influencing their cognitive, emotional, and social functioning. Here, we report a study on prenatal PM2.5 exposure and neurobehavioral development focusing on different time points in the first years of life. METHODS: This study was part of the ENVIRONAGE birth cohort that follows mother-child pairs longitudinally. First, the Neonatal Behavioral Assessment Scale (NBAS) was employed on 88 newborns aged one to two months to assess their autonomic/physiological regulation, motor organisation, state organisation/regulation, and attention/social interaction. Second, our study included 393 children between the ages of four and six years, for which the Strengths and Difficulties Questionnaire (SDQ) was used to assess the children's emotional problems, hyperactivity, conduct problems, peer relationship, and prosocial behaviour. Prenatal PM2.5 exposure was determined using a high-resolution spatial-temporal method based on the maternal address. Multiple linear and multinomial logistic regression models were used to analyse the relationship between prenatal PM2.5 exposure and neurobehavioral development in newborns and children, respectively. RESULTS: A 5 µg/m³ increase in first-trimester PM2.5 concentration was associated with lower NBAS range of state cluster scores (-6.11%; 95%CI: -12.00 to -0.23%; p = 0.04) in one-to-two-month-old newborns. No other behavioural clusters nor the reflexes cluster were found to be associated with prenatal PM2.5 exposure. Furthermore, a 5 µg/m³ increment in first-trimester PM2.5 levels was linked with higher odds of a child experiencing peer problems (Odds Ratio (OR) = 3.89; 95%CI: 1.39 to 10.87; p = 0.01) at ages four to six. Additionally, a 5 µg/m³ increase in second-trimester PM2.5 concentration was linked to abnormal prosocial behaviour (OR = 0.49; 95%CI: 0.25 to 0.98; p = 0.04) at four to six years old. No associations were found between in utero PM2.5 exposure and hyperactivity or conduct problems. CONCLUSIONS: Our findings suggest that prenatal exposure to PM may impact neurobehavioural development in newborns and preschool children. We identified sensitive time windows during early-to-mid pregnancy, possibly impacting stage changes in newborns and peer problems and prosocial behaviour in children.

Impact of short-term exposure to air pollution on natural mortality and vulnerable populations: a multi-city case-crossover analysis in Belgium.

BACKGROUND: The adverse effect of air pollution on mortality is well documented worldwide but the identification of more vulnerable populations at higher risk of death is still limited. The aim of this study was to evaluate the association between natural mortality (overall and cause-specific) and short-term exposure to five air pollutants (PM2.5, PM10, NO2, O3 and black carbon) and identify potential vulnerable populations in Belgium. METHODS: We used a time-stratified case-crossover design with conditional logistic regressions to assess the relationship between mortality and air pollution in the nine largest Belgian agglomerations. Then, we performed a random-effect meta-analysis of the pooled results and described the global air pollution-mortality association. We carried out stratified analyses by individual characteristics (sex, age, employment, hospitalization days and chronic preexisting health conditions), living environment (levels of population density, built-up areas) and season of death to identify effect modifiers of the association. RESULTS: The study included 304,754 natural deaths registered between 2010 and 2015. We found percentage increases for overall natural mortality associated with 10 µg/m3 increases of air pollution levels of 0.6% (95% CI: 0.2%, 1.0%) for PM2.5, 0.4% (0.1%, 0.8%) for PM10, 0.5% (-0.2%, 1.1%) for O3, 1.0% (0.3%, 1.7%) for NO2 and 7.1% (-0.1%, 14.8%) for black carbon. There was also evidence for increases of cardiovascular and respiratory mortality. We did not find effect modification by individual characteristics (sex, age, employment, hospitalization days). However, this study suggested differences in risk of death for people with preexisting conditions (thrombosis, cardiovascular diseases, asthma, diabetes and thyroid affections), season of death (May-September vs October-April) and levels of built-up area in the neighborhood (for NO2). CONCLUSIONS: This work provided evidence for the adverse health effects of air pollution and contributed to the identification of specific population groups. These findings can help to better define public-health interventions and prevention strategies.

Association of air pollution and green space with all-cause general practitioner and emergency room visits: A cross-sectional study of young people and adults living in Belgium.

BACKGROUND: Residing in areas with lower levels of air pollution and higher green space is beneficial to physical and mental health. We investigated associations of PM2.5, tree cover and grass cover with in-hours and out-of-hours GP visits and ER visits, for young people and adults. We estimated potential cost savings of GP visits attributable to high PM2.5. METHODS: We linked individual-level health insurance claims data of 315,123 young people (10-24 years) and 885,988 adults (25-64 years) with census tract-level PM2.5, tree cover and grass cover. Deploying negative binomial generalized linear mixed models, we estimated associations between quartile exposures and the three outcome measures. RESULTS: For in-hours and out-of-hours GP visits, among young people as well as adults, statistically significant pairwise differences between quartiles suggested increasing beneficial effects with lower PM2.5. The same outcomes were statistically significantly less frequent in quartiles with highest tree cover (>30.00%) compared to quartiles with lower tree cover, but otherwise pairwise differences were not statistically significant. These associations largely persisted in rural and urban areas. Among adults living in urban areas lower grass cover was associated with increased in-hours GP visits and ER visits. Assuming causality, reducing PM2.5 levels to the lowest quartile (4.91-7.49 µg/m³), among adults, 195,964 in-hours and 74,042 out-of-hours GP visits could be avoided annually. Among young people, 27,457 in-hours and 22,423 out-of-hours GP visits could be avoided annually. Nationally, this amounts to an annual potential cost saving of €43 million (€5.7 million in out-of-pocket payments and €37.2 million in compulsory health insurance). CONCLUSION: Higher ambient PM2.5 and lower tree cover show associations with higher non-urgent and urgent medical care utilization. These findings confirm the importance of reducing air pollution and fostering green zones, and that such policies may contribute positively to economic growth.

The association between ambient particulate matter exposure and the telomere-mitochondrial axis of aging in newborns.

BACKGROUND: Particulate matter (PM) is associated with aging markers at birth, including telomeres and mitochondria. It is unclear whether markers of the core-axis of aging, i.e. tumor suppressor p53 (p53) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), are associated with prenatal air pollution and whether there are underlying mechanisms. METHODS: 556 mother-newborn pairs from the ENVIRONAGE birth cohort were recruited at the East Limburg Hospital in Genk (Belgium). In placenta and cord blood, telomere length (TL) and mitochondrial DNA content (mtDNAc) were measured using quantitative real-time polymerase chain reaction (qPCR). In cord plasma, p53 and PGC-1α protein levels were measured using ELISA. Daily ambient PM2.5 concentrations during gestation were calculated using a spatial temporal interpolation model. Distributed lag models (DLMs) were applied to assess the association between prenatal PM2.5 exposure and each molecular marker. Mediation analysis was performed to test for underlying mechanisms. RESULTS: A 5 µg/m3 increment in PM2.5 exposure was associated with -11.23 % (95 % CI: -17.36 % to -4.65 %, p = 0.0012) and -7.34 % (95 % CI: -11.56 % to -2.92 %, p = 0.0014) lower placental TL during the entire pregnancy and second trimester respectively, and with -12.96 % (95 % CI: -18.84 % to -6.64 %, p < 0.001) lower placental mtDNAc during the third trimester. Furthermore, PM2.5 exposure was associated with a 12.42 % (95 % CI: -1.07 % to 27.74 %, p = 0.059) higher cord plasma p53 protein level and a -3.69 % (95 % CI: -6.97 % to -0.31 %, p = 0.033) lower cord plasma PGC-1α protein level during the third trimester. Placental TL mediated 65 % of the negative and 17 % of the positive association between PM2.5 and placental mtDNAc and cord plasma p53 protein levels, respectively. CONCLUSION: Ambient PM2.5 exposure during pregnancy is associated with markers of the core-axis of aging, with TL as a mediating factor. This study strengthens the hypothesis of the air pollution induced core-axis of aging, and may unravel a possible underlying mediating mechanism in an early-life epidemiological context.

Are air quality perception and PM2.5 exposure differently associated with cardiovascular and respiratory disease mortality in Brussels? Findings from a census-based study.

BACKGROUND: There is ample evidence that air pollution increases mortality risk, but most studies are based on modelled estimates of air pollution, while the subjective perception of air quality is scarcely assessed. We aimed to compare the effects of objective and subjective exposure to air pollution on cardiorespiratory mortality in Brussels, Belgium. METHODS: Data consisted of the 2001 Belgian census linked to registry-based mortality data for the follow-up period 2001-2014. We included individuals aged >30 years of age residing in Brussels at baseline (2001). Air pollution exposure was assessed with objective (modelled annual mean concentrations of PM2.5 in micrograms per cubic metre, µg/m3) and subjective indicators (poor self-reported air quality perception in the census). We used Cox Proportional Hazard models with age as the underlying time scale to evaluate associations with cardiovascular disease (CVD) and respiratory disease mortality, and separately, ischaemic heart disease (IHD), cerebrovascular disease, and COPD excluding asthma mortality. We specified single- and two-exposure models and evaluated effect modification by neighbourhood unemployment rate. RESULTS: 437,340 individuals were included at baseline. During follow-up (2001-2014), 22,821 (5%) individuals had died from CVDs and 8572 (2%) from respiratory diseases. In single-exposure models, PM2.5 was significantly associated with an increased risk in CVD and IHD mortality (e.g. for IHD, per 5 µg/m3 increase: Hazard Ratio, HR:1.22, 95%CI:1.08-1.37), and poor air quality perception with COPD excluding asthma mortality (HR:1.23, 95%CI:1.15-1.33). Associations remained significant in the two-exposure models, and additionally, perception was associated with respiratory disease mortality. Associations became gradually stronger with increasing neighbourhood unemployment rate [e.g. in the highest, Q3: PM2.5 and cerebrovascular disease mortality (HR:1.53, 95%CI:1.04-2.24)]. CONCLUSION: Our findings suggest that objective and subjective exposure to air pollution increased the risk of dying from cardiovascular and respiratory diseases respectively in Brussels. These results encourage policies reducing pollution load in Brussels whilst considering socio-economic inequalities.

In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates.

Mitochondria are sensitive to oxidative stress, which can be caused by traffic-related air pollution. Placental mitochondrial DNA (mtDNA) mutations have been previously linked with air pollution. However, the relationship between prenatal air pollution and cord-blood mtDNA mutations has been poorly understood. Therefore, we hypothesized that prenatal particulate matter (PM2.5) and NO2 exposures are associated with cord-blood mtDNA heteroplasmy. As part of the ENVIRONAGE cohort, 200 mother-newborn pairs were recruited. Cord-blood mitochondrial single-nucleotide polymorphisms were identified by whole mitochondrial genome sequencing, and heteroplasmy levels were evaluated based on the variant allele frequency (VAF). Outdoor PM2.5 and NO2 concentrations were determined by a high-resolution spatial-temporal interpolation method based on the maternal residential address. Distributed lag linear models were used to determine sensitive time windows for the association between NO2 exposure and cord-blood mtDNA heteroplasmy. A 5 µg/m3 increment in NO2 was linked with MT-D-Loop16311T>C heteroplasmy from gestational weeks 17-25. MT-CYTB14766C>T was negatively associated with NO2 exposure in mid pregnancy, from weeks 14-17, and positively associated in late pregnancy, from weeks 31-36. No significant associations were observed with prenatal PM2.5 exposure. This is the first study to show that prenatal NO2 exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.

Urban green spaces and suicide mortality in Belgium (2001-2011): A census-based longitudinal study.

BACKGROUND: Exposure to green spaces is associated with improved mental health and may reduce risk of suicide. Here, we investigate the association between long-term exposure to residential surrounding greenness and suicide mortality. METHODS: We used data from the 2001 Belgian census linked to mortality register data (2001-2011). We included all registered individuals aged 18 years or older at baseline (2001) residing in the five largest urban areas in Belgium (n = 3,549,514). Suicide mortality was defined using the tenth revision of the World Health Organisation International Classification of Diseases (ICD-10) codes X60-X84, Y10-Y34, and Y870. Surrounding greenness was measured using the Normalized Difference Vegetation Index (NDVI) within a 300 m and 1,000 m buffer around the residential address at baseline. To assess the association between residential surrounding greenness and suicide mortality, we applied Cox proportional hazards models with age as the underlying time scale. Models were adjusted for age, sex, living arrangement, migrant background, educational attainment, neighbourhood socio-economic position. We additionally explored potential mediation by residential outdoor nitrogen dioxide (NO2) concentrations. Finally, we assessed potential effect modification by various socio-demographic characteristics of the population (sex, age, educational attainment, migrant background, and neighbourhood socio-economic position). Associations are expressed as hazard ratios and their 95% confidence intervals (CI) for an interquartile range (IQR) increase in residential surrounding greenness. RESULTS: We observed a 7% (95%CI 0.89-0.97) and 6% (95%CI 0.90-0.98) risk reduction of suicide mortality for an IQR increase in residential surrounding greenness for buffers of 300 m and 1,000 m, respectively. Furthermore, this association was independent of exposure to NO2. After stratification, the inverse association was only apparent among women, and residents of Belgian origin, and that it was stronger among residents aged 36 or older, those with high level of education, and residents of most deprived neighbourhoods. CONCLUSION: Our results suggest that urban green spaces may protect against suicide mortality, but this beneficial effect may not be equally distributed across all strata of the population.

Long-term exposure to residential green spaces and site-specific cancer mortality in urban Belgium: A 13-year follow-up cohort study.

BACKGROUND: Residing in greener areas may decrease the burden of chronic diseases, but the association with cancer is unclear. We studied the associations between residential green spaces and site-specific cancer mortality in urban Belgium. METHODOLOGY: We linked the 2001 Belgian census, register mortality data for 2001-2014, and environmental information (green spaces and air pollution) at baseline residence (2001). We included residents from the largest Belgian urban areas aged ≥ 30 years at baseline. Exposure to residential green spaces was assessed using the Normalized Difference Vegetation Index (NDVI), Urban Atlas, and perceived neighbourhood greenness (from the census). We used Cox proportional hazards models to obtain hazard ratios (HR) and their 95 % confidence intervals (95 %CI) of the mortality risk from lung, colorectal, breast (in women) and prostate cancer (in men) per interquartile range increment in residential green spaces. We further analyzed the role of outdoor air pollution and effect modification by age and socioeconomic position (SEP) in main associations. RESULTS: 2,441,566 individuals were included at baseline. During follow-up, 1.2 % died from lung cancer, 0.6 % from colorectal cancer, 0.8 % from breast cancer, and 0.6 % from prostate cancer. After adjustment, higher exposure to green spaces was associated with a reduced mortality risk from lung cancer and breast cancer [e.g., for NDVI within 300 m, HR:0.946 (95 %CI:0.924,0.970), and HR:0.927 (95 %CI:0.892,0.963), respectively], but not with colorectal or prostate cancer mortality. For the latter, a suggestive hazardous effect of green spaces was found. Air pollution seemed to have only a marginal role. Beneficial effects of greenspace were generally stronger in < 65-year-old, but no clear trend by SEP was found. CONCLUSIONS: Our findings suggest that residing in green areas could decrease mortality risk from lung and breast cancer, potentially independent from air pollution. Future studies should consider different indicators of greenspace exposure and investigate potential pathways underlying the associations.

In utero particulate matter exposure in association with newborn mitochondrial ND4L10550A>G heteroplasmy and its role in overweight during early childhood.

BACKGROUND: Mitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5 exposure is associated with cord blood MT-ND4L10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>G heteroplasmy in overweight during early childhood is investigated. METHODS: This study included 386 mother-newborn pairs. Outdoor PM2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>G heteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5 exposure on childhood overweight mediated by cord blood MT-ND4L10550A>G heteroplasmy. RESULTS: Prenatal PM2.5 exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51; p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5 exposure was associated with cord blood MT-ND4L10550A>G heteroplasmy from gestational week 9 - 13. The largest effect was observed in week 10, where a 5 µg/m3 increment in PM2.5 was linked with cord blood MT-ND4L10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>G heteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50; p = 0.02). The effect of prenatal PM2.5 exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>G heteroplasmy. CONCLUSIONS: Cord blood MT-ND4L10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>G heteroplasmy in the association between PM2.5 exposure and childhood overweight.

Long-term exposure to residential greenness and neurodegenerative disease mortality among older adults: a 13-year follow-up cohort study.

BACKGROUND: Living in greener areas is associated with slower cognitive decline and reduced dementia risk among older adults, but the evidence with neurodegenerative disease mortality is scarce. We studied the association between residential surrounding greenness and neurodegenerative disease mortality in older adults. METHODS: We used data from the 2001 Belgian census linked to mortality register data during 2001-2014. We included individuals aged 60 years or older and residing in the five largest Belgian urban areas at baseline (2001). Exposure to residential surrounding greenness was assessed using the 2006 Normalized Difference Vegetation Index (NDVI) within 500-m from residence. We considered all neurodegenerative diseases and four specific outcomes: Alzheimer's disease, vascular dementia, unspecified dementia, and Parkinson's disease. We fitted Cox proportional hazard models to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the associations between one interquartile range (IQR) increment in surrounding greenness and neurodegenerative disease mortality outcomes, adjusted for census-based covariates. Furthermore, we evaluated the potential role of 2010 air pollution (PM2.5 and NO2) concentrations, and we explored effect modification by sociodemographic characteristics. RESULTS: From 1,134,502 individuals included at baseline, 6.1% died from neurodegenerative diseases during follow-up. After full adjustment, one IQR (0.22) increment of surrounding greenness was associated with a 4-5% reduction in premature mortality from all neurodegenerative diseases, Alzheimer's disease, vascular and unspecified dementia [e.g., for Alzheimer's disease mortality: HR 0.95 (95%CI: 0.93, 0.98)]. No association was found with Parkinson's disease mortality. Main associations remained for all neurodegenerative disease mortality when accounting for air pollution, but not for the majority of specific mortality outcomes. Associations were strongest in the lower educated and residents from most deprived neighbourhoods. CONCLUSIONS: Living near greener spaces may reduce the risk of neurodegenerative disease mortality among older adults, potentially independent from air pollution. Socioeconomically disadvantaged groups may experience the greatest beneficial effect.

Short-Term exposure to ambient air pollution and onset of work incapacity related to mental health conditions.

The OECD estimates that greater work absenteeism is one of the main drivers behind the impact of air pollution on gross domestic product loss, but research linking air pollution with work absenteeism is scarce. With air pollution increasingly being linked to poor mental health, and poor mental health having become one of the main reasons for work absenteeism, we examined whether the onset of work incapacity related to mental health conditions is associated with short-term fluctuations in ambient black carbon (BC), nitrogen dioxide (NO2), ozone (O3), and particulate matter 2.5 (PM2.5), estimating the contributions of these pollutants jointly, while accounting for relative humidity, total solar radiation and temperature. We conducted a bidirectional time-stratified case-crossover study with daily air pollution estimates by municipality linked with 12 270 events of work incapacity related to mental health conditions in 2019 in Belgium. We ran single- and multi-pollutant conditional logistic regression models for three different exposure windows (lag 0, 0-1 and 0-2), considering potential confounding by relative humidity and total solar radiation. We observed positive associations between work incapacity related to mental health conditions and BC, NO2, and O3 exposure, but findings for PM2.5 were inconsistent. Results from multi-pollutant models showed a 12% higher risk of work incapacity for an IQR increase in NO2 and O3 at the day of the event (lag 0), with estimates increasing to about 26% for average concentrations up to two days before the event (lag 0-2). We found evidence for effect modification by age and season in the association with NO2, with highest effect estimates in the age group 40-49 years and in spring and summer. For O3, we observed effect modification by type of mental health problem. This country-wide study suggests that air pollution aggravates within 48 h a likely existing propensity to enter work incapacity because of mental health conditions.

Long-term exposure to objective and perceived residential greenness and diabetes mortality: A census-based cohort study.

BACKGROUND: Residing close to green spaces might reduce diabetes mellitus (DM) risk; however, evidence for diabetes mortality is limited. Moreover, individual and neighbourhood social factors may determine DM risk. Exposure to green spaces may also depend on socioeconomic position (SEP). This study examined the associations between residential greenness and diabetes-related mortality, and the role of the social environment in these associations. METHODS: We used the 2001 Belgian census linked to mortality register data for the period 2001-2014. We included individuals aged 40-79 years old and residing in the five largest Belgian urban areas at baseline. Exposure to residential greenness was assessed with surrounding greenness using the Normalized Difference Vegetation Index (NDVI) within 500-m of residence (objective indicator), and perceived neighbourhood greenness (subjective indicator). We conducted mixed-effects Cox proportional hazards models to obtain hazard ratios (HR) for diabetes-related mortality per interquartile range (IQR) increments of residential greenness. We assessed effect modification by social factors through stratification. RESULTS: From 2,309,236 individuals included at baseline, 1.2% died from DM during follow-up. Both residential greenness indicators were inversely associated with diabetes-related mortality after adjustment for individual social factors. After controlling for neighbourhood SEP, the beneficial association with surrounding greenness disappeared [HR 1.02 (95%CI:0.99,1.06)], but persisted with perceived neighbourhood greenness [HR 0.93 (95%CI:0.91,0.95)]. After stratification the inverse associations with perceived neighbourhood greenness were strongest for women, the lowest educated, and individuals residing in least deprived neighbourhoods. CONCLUSIONS: Our findings suggest that an overall positive perception of neighbourhood green spaces reduces independently the risk of diabetes-related mortality, regardless of the neighbourhood social environment. Nevertheless, neighbourhood SEP may be a strong confounder in the associations between diabetes-related mortality and greenness indicators derived from satellite images. Perception factors not captured by objective measurements of green spaces are potentially relevant in the association with DM, especially among disadvantaged groups.

Variability in the association between long-term exposure to ambient air pollution and mortality by exposure assessment method and covariate adjustment: A census-based country-wide cohort study.

BACKGROUND: Ambient air pollution exposure has been associated with higher mortality risk in numerous studies. We assessed potential variability in the magnitude of this association for non-accidental, cardiovascular disease, respiratory disease, and lung cancer mortality in a country-wide administrative cohort by exposure assessment method and by adjustment for geographic subdivisions. METHODS: We used the Belgian 2001 census linked to population and mortality register including nearly 5.5 million adults aged ≥30 (mean follow-up: 9.97 years). Annual mean concentrations for fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) were assessed at baseline residential address using two exposure methods; Europe-wide hybrid land use regression (LUR) models [100x100m], and Belgium-wide interpolation-dispersion (RIO-IFDM) models [25x25m]. We used Cox proportional hazards models with age as the underlying time scale and adjusted for various individual and area-level covariates. We further adjusted main models for two different area-levels following the European Nomenclature of Territorial Units for Statistics (NUTS); NUTS-1 (n = 3), or NUTS-3 (n = 43). RESULTS: We found no consistent differences between both exposure methods. We observed most robust associations with lung cancer mortality. Hazard Ratios (HRs) per 10 µg/m3 increase for NO2 were 1.060 (95%CI 1.042-1.078) [hybrid LUR] and 1.040 (95%CI 1.022-1.058) [RIO-IFDM]. Associations with non-accidental, respiratory disease and cardiovascular disease mortality were generally null in main models but were enhanced after further adjustment for NUTS-1 or NUTS-3. HRs for non-accidental mortality per 5 µg/m3 increase for PM2.5 for the main model using hybrid LUR exposure were 1.023 (95%CI 1.011-1.035). After including random effects HRs were 1.044 (95%CI 1.033-1.057) [NUTS-1] and 1.076 (95%CI 1.060-1.092) [NUTS-3]. CONCLUSION: Long-term air pollution exposure was associated with higher lung cancer mortality risk but not consistently with the other studied causes. Magnitude of associations varied by adjustment for geographic subdivisions, area-level socio-economic covariates and less by exposure assessment method.

Dynamics of skin microvascular blood flow in 4-6-year-old children in association with pre- and postnatal black carbon and particulate air pollution exposure.

BACKGROUND: A growing body of evidence indicates that cardiovascular health in adulthood, particularly that of the microcirculation, could find its roots during prenatal development. In this study, we investigated the association between pre- and postnatal air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. METHODS: In 139 children between the ages of 4 and 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC), particulate (PM10 and PM2.5) air pollution, and nitrogen dioxide (NO2) levels were modelled for each participant's home address using a high-resolution spatiotemporal model for multiple time windows. We assessed the association between skin hyperemia and pre- and postnatal air pollution using multiple regression models while adjusting for relevant covariates. RESULTS: Residential BC exposure during the whole pregnancy averaged (IQR) 1.42 (1.22-1.58) µg/m3, PM10 18.88 (16.64 - 21.13) µg/m3, PM2.5 13.67 (11.5 - 15.56) µg/m3 and NO2 18.39 (15.52 - 20.31) µg/m3. An IQR increment in BC exposure during the third trimester of pregnancy was associated with an 11.5 % (95% CI: -20.1 to -1.9; p = 0.020) lower skin hyperemia. Similar effect estimates were retrieved for PM10, PM2.5 and NO2 (respectively 13.9 % [95% CI: -21.9 to -3.0; p = 0.003], 17.0 % [95% CI: -26.7 to -6.1; p = 0.004] and 12.7% [95 % CI: -22.2 to -1.9; p = 0.023] lower skin hyperemia). In multipollutant models, PM2.5 showed the strongest inverse association with skin hyperemia. Postnatal exposure to BC, PM10, PM2.5 or NO2, was not associated with skin hyperemia at the age of 4 to 6, and did not alter the previous reported prenatal associations when taken into account. CONCLUSION: Our findings support that BC, particulate air pollution, and NO2 exposure, even at low concentrations, during prenatal life, can have long-lasting consequences for the microvasculature. This proposes a role of prenatal air pollution exposures over and beyond postnatal exposure in the microvascular alterations which were persistent into childhood.

Social inequalities in the associations between urban green spaces, self-perceived health and mortality in Brussels: Results from a census-based cohort study.

This study examines the associations between residential urban green spaces (UGS) and self-perceived health and natural cause mortality, applying an intersectional approach across gender, education and migrant background. We used data from the 2001 Belgian census linked to register data on emigration and mortality for the period 2001-2014, including 571,558 individuals aged 16-80 residing in Brussels (80% response rate). Residential UGS were assessed with the Normalized Difference Vegetation Index (NDVI) within a 300 m buffer from the residential address and perceived neighbourhood greenness. Multilevel logistic and Cox proportional hazards regression models were conducted to estimate associations between UGS and poor self-perceived health at baseline and natural cause mortality during follow-up. Residential UGS were inversely associated with both outcomes, but there were differences between groups. The strongest beneficial associations among women were found in the lower educated, regardless of their migrant background. For men the strongest association was found in those with tertiary education and Belgian origin. No significant beneficial associations were found in men originating from low and middle-income countries. Applying an intersectionality approach is crucial to understand health inequalities related to UGS exposure. Further research in different geographical contexts is needed to contrast our findings.

Residential exposure to air pollution and access to neighborhood greenspace in relation to hair cortisol concentrations during the second and third trimester of pregnancy.

BACKGROUND: Exposure to air pollution during pregnancy has been associated with adverse pregnancy outcomes in studies worldwide, other studies have described beneficial effects of residential greenspace on pregnancy outcomes. The biological mechanisms that underlie these associations are incompletely understood. A biological stress response, which implies release of cortisol, may underlie associations of air pollution exposure and access to neighborhood greenspaces with health. METHODS: We explored residential exposure to air pollution and residential access to neighborhood greenspaces in relation to hair cortisol concentrations of participants in a prospective pregnancy cohort study in Flanders, Belgium. Hair samples were collected at the end of the second pregnancy trimester (n = 133) and shortly after delivery (n = 81). Cortisol concentrations were measured in 3-cm scalp-near hair sections, to reflect second and third pregnancy trimester cortisol secretion. We estimated long-term (3 months before sampling) residential exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC), assessed residential distance to major roads and residential access to neighborhood greenspaces (NHGS). Associations between residential exposures and hair cortisol concentrations were studied using linear regression models while adjusting for season of sampling. RESULTS: Three-month mean residential NO2 and BC concentrations were positively associated with third pregnancy trimester hair cortisol concentrations (p = 0.008 and p = 0.017). Access to a large NHGS (10 ha or more within 800 m from residence) was negatively associated with third trimester hair cortisol concentrations (p = 0.019). Access to a large NHGS significantly moderated the association between residential proximity to major roads and second trimester hair cortisol concentrations (p = 0.021). Residential distance to major roads was negatively associated with second trimester hair cortisol concentrations of participants without access to a large NHGS (p = 0.003). The association was not significant for participants with access to a large NHGS. The moderation tended towards significance in the third pregnancy trimester (p < 0.10). CONCLUSIONS: Our findings suggest a positive association between long-term residential exposure to air pollution and biological stress during pregnancy, residential access to neighborhood greenspaces may moderate the association. Further research is needed to confirm our results. TRIAL REGISTRATION: The IPANEMA study is registered under number  NCT02592005 at clinicaltrials.gov .

Residing in urban areas with higher green space is associated with lower mortality risk: A census-based cohort study with ten years of follow-up.

BACKGROUND: Epidemiological studies suggest that residing close to green space reduce mortality rates. We investigated the relationship between long-term exposure to residential green space and non-accidental and cardio-respiratory mortality. METHODS: We linked the Belgian 2001 census to population and mortality register follow-up data (2001-2011) among adults aged 30 years and older residing in the five largest urban areas in Belgium (n = 2,185,170 and mean follow-up time 9.4 years). Residential addresses were available at baseline. Exposure to green space was defined as 1) surrounding greenness (2006) [normalized difference vegetation index (NDVI) and modified soil-adjusted vegetation index (MSAVI2)] within buffers of 300 m, 500 m, and 1000 m; 2) surrounding green space (2006) [Urban Atlas (UA) and CORINE Land Cover (CLC)] within buffers of 300 m, 500 m, and 1000 m; and 3) perceived neighborhood green space (2001). Cox proportional hazards models with age as the underlying time scale were used to probe into cause-specific mortality (non-accidental, respiratory, COPD, cardiovascular, ischemic heart disease (IHD), and cerebrovascular). Models were adjusted for several sociodemographic variables (age, sex, marital status, country of birth, education level, employment status, and area mean income). We further adjusted our main models for annual mean (2010) values of ambient air pollution (PM2.5, PM10, NO2 and BC, one at a time), and we additionally explored potential mediation with the aforementioned pollutants. RESULTS: Higher degrees of residential green space were associated with lower rates of non-accidental and respiratory mortality. In fully adjusted models, hazard ratios (HR) per interquartile range (IQR) increase in NDVI 500 m buffer (IQR: 0.24) and UA 500 m buffer (IQR: 0.31) were 0.97 (95%CI 0.96-0.98) and 0.99 (95%CI 0.98-0.99) for non-accidental mortality, and 0.95 (95%CI 0.93-0.98) and 0.97 (95%CI 0.96-0.99) for respiratory mortality. For perceived neighborhood green space, HRs were 0.93 (95%CI 0.92-0.94) and 0.94 (95%CI 0.91-0.98) for non-accidental and respiratory mortality, respectively. The observed lower mortality risks associated with residential exposure to green space were largely independent from exposure to ambient air pollutants. CONCLUSION: We observed evidence for lower mortality risk in associations with long-term residential exposure to green space in most but not all studied causes of death in a large representative cohort for the five largest urban areas in Belgium. These findings support the importance of the availability of residential green space in urban areas.

Ambient air pollution exposure during the late gestational period is linked with lower placental iodine load in a Belgian birth cohort.

BACKGROUND: Adequate intake of iodine is required for the production of thyroid hormones and contributes in pregnant women to a healthy brain development and growth in their offspring. To date, some evidence exists that fine particulate air pollution is linked with the fetal thyroid hormone homeostasis. However, possible effects of air pollutants on the placental iodine storage have not been investigated so far. OBJECTIVES: We investigated the association between air pollution exposure to particulate matter with a diameter less than 2.5 µm (PM2.5), NO2, and black carbon and the placental iodine load. METHODS: The current study is part of the ENVIRONAGE birth cohort and included 470 mother-newborn pairs. Iodine concentrations were measured in placental tissue. A high-resolution air pollution model was used to estimate the daily exposure to PM2.5, NO2, and black carbon over the entire pregnancy based on the maternal residential addresses. Distributed lag nonlinear models (DLNMs) were used to estimate gestational week-specific associations between placental iodine concentrations and the air pollutants to understand the impact of specific exposure windows. RESULTS: PM2.5 showed a positive association with placental iodine concentration between the 16th and 22nd week of gestation. In contrast, a significant inverse association between PM2.5 and placental iodine concentration was observed in gestational weeks 29-35. The effect estimate, for a 5 µg/m3 increment in PM2.5 concentration, was the strongest at week 32 (ß -0.11 µg/kg; 95%CI: -0.18 to -0.03). No associations were observed between placental iodine concentrations and NO2 or black carbon. Assuming causality, we estimated that placental iodine mediated 26% (-0.33 pmol/L; 95%CI: -0.70 to 0.04 pmol/L) of the estimated effect of a 5 µg/m3 increment in PM2.5 exposure on cord blood free thyroxine (FT4) concentrations. CONCLUSION: In utero exposure to particulate matter during the third trimester of pregnancy is linked with a lower placental iodine load. Furthermore, the effect of air pollution on cord blood FT4 levels was partially mediated by the placental iodine load.

Residential urban greenspace and hypertension: A comparative study in two European cities.

BACKGROUND: Living in green areas has been associated with several health benefits; however, the available evidence on such benefits for hypertension is still limited. This study aimed to investigate and compare the association between residential exposure to greenspace and hypertension in Barcelona, Spain and Brussels, Belgium. METHODS: This cross-sectional study was based on data from the 2016 Barcelona Health Interview Survey (HIS) (n = 3400) and the 2013 Belgian HIS (n = 2335). Both surveys were harmonized in terms of outcomes, confounders and exposure assessment. Residential exposure to greenspace was characterized as 1) surrounding greenspace (normalized difference vegetation index (NDVI) and modified soil-adjusted vegetation index 2 (MSAVI2)) across buffers of 100 m, 300 m, and 500 m; 2) surrounding green space across 300 m and 500 m buffers; and 3) Euclidean distance to the nearest green space. Our outcome was self-reported hypertension. We developed logistic regression models to evaluate the city-specific association between each greenspace measure and hypertension, adjusting for relevant covariates. RESULTS: One interquartile range (IQR) increase in residential distance to the nearest green space was associated with higher risk of hypertension in Barcelona [odds ratio (OR): 1.15; 95%CI 1.03-1.29 (IQR: 262.2)], but not in Brussels [OR: 0.95; 95%CI 0.77-1.17 (IQR: 215.2)]. Stratified analyses suggested stronger associations in older participants (≥65 years) for both cities. Findings for residential surrounding green space and greenspace were not conclusive. However, in Brussels, we found protective associations in older participants for both residential surrounding greenspace metrics [NDVI 300 m buffer OR: 0.51; 95%CI 0.32-0.81 (IQR: 0.21) and MSAVI2 300 m buffer OR: 0.51; 95%CI 0.32-0.83 (IQR: 0.18)]. We did not find any indication for the modification of our evaluated associations by sex and education level. CONCLUSION: Our study suggests that living closer to greenspace could be associated with lower risk of hypertension, particularly in older age. Future research is needed to replicate our findings in other settings and shed light on potential underlying mechanism(s).

Prenatal particulate air pollution exposure and expression of the miR-17/92 cluster in cord blood: Findings from the ENVIRONAGE birth cohort.

BACKGROUND: Air pollution exposure during pregnancy is an important environmental health issue. Epigenetics mediate the effects of prenatal exposure and could increase disease predisposition in later life. The oncogenic miR-17/92 cluster is involved in normal development and disease. OBJECTIVES: Here, for the first time the potential prenatal effects of particulate matter with a diameter<2.5 µm (PM2.5) exposure on expression of the miR-17/92 cluster in cord blood are explored. METHODS: In 370 mother-newborn pairs from the ENVIRONAGE birth cohort, expression of three members of the miR-17/92 cluster was measured in cord blood by qRT-PCR. Expression of C-MYC and CDKN1A, a cluster activator and a target gene, respectively, was also analyzed. Multivariable linear regression models were used to associate the relative m(i)RNA expression with prenatal PM2.5 exposure. RESULTS: PM2.5 exposure averaged (10th-90th percentile) 11.7 (9.0-14.4) µg/m3 over the entire pregnancy. In cord blood, miR-17 and miR-20a showed a -45.0% (95%CI: -55.9 to -31.4, p < 0.0001) and a -33.7% (95%CI: -46.9 to -17.2, p = 0.0003), decrease in expression in association with first trimester PM2.5 exposure, and a -32.5% (95%CI: -45.6 to -16.3, p = 0.0004) and -23.3% (95%CI: -38.1 to -4.8, p = 0.02), respectively, decrease in expression in association with PM2.5 exposure during the entire pregnancy. In association with third trimester PM2.5 exposure, a reduction of -25.8% (95%CI: -40.2 to -8.0, p = 0.007) and -14.2% (95%CI: -27.7 to 1.9, p = 0.08), for miR-20a and miR-92a expression, respectively, was identified. Only miR-92a expression (-15.7%, 95%CI: -27.3 to -2.4, p = 0.02) was associated with PM2.5 exposure during the last month of pregnancy. C-MYC expression was downregulated in cord blood in association with prenatal PM2.5 exposure during the first trimester and the entire pregnancy, in the adjusted model. DISCUSSION: Lower expression levels of the miR-17/92 cluster in cord blood in association with increased prenatal PM2.5 exposure were observed. Whether this oncogenic microRNA cluster plays a role in trans-placental carcinogenesis remains to be elucidated.