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.

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.

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.

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.

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.

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.

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.

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 .

Children's microvascular traits and ambient air pollution exposure during pregnancy and early childhood: prospective evidence to elucidate the developmental origin of particle-induced disease.

BACKGROUND: Particulate matter exposure during in utero life may entail adverse health outcomes later in life. The microvasculature undergoes extensive, organ-specific prenatal maturation. A growing body of evidence shows that cardiovascular disease in adulthood is rooted in a dysfunctional fetal and perinatal development, in particular that of the microcirculation. We investigate whether prenatal or postnatal exposure to PM2.5 (particulate matter with a diameter ≤ 2.5 µm) or NO2 is related to microvascular traits in children between the age of four and six. METHODS: We measured the retinal microvascular diameters, the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), and the vessel curvature by means of the tortuosity index (TI) in young children (mean [SD] age 4.6 [0.4] years), followed longitudinally within the ENVIRONAGE birth cohort. We modeled daily prenatal and postnatal PM2.5 and NO2 exposure levels for each participant's home address using a high-resolution spatiotemporal model. RESULTS: An interquartile range (IQR) increase in PM2.5 exposure during the entire pregnancy was associated with a 3.85-µm (95% CI, 0.10 to 7.60; p = 0.04) widening of the CRVE and a 2.87-µm (95% CI, 0.12 to 5.62; p = 0.04) widening of the CRAE. For prenatal NO2 exposure, an IQR increase was found to widen the CRVE with 4.03 µm (95% CI, 0.44 to 7.63; p = 0.03) and the CRAE with 2.92 µm (95% CI, 0.29 to 5.56; p = 0.03). Furthermore, a higher TI score was associated with higher prenatal NO2 exposure. We observed a postnatal effect of short-term PM2.5 exposure on the CRAE and a childhood NO2 exposure effect on both the CRVE and CRAE. CONCLUSIONS: Our results link prenatal and postnatal air pollution exposure with changes in a child's microvascular traits as a fundamental novel mechanism to explain the developmental origin of cardiovascular disease.

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 cord blood homocysteine in newborns: Results from the ENVIRONAGE birth cohort.

INTRODUCTION: Particulate air pollution is probably causally related to increased risk of cardiovascular disease. Plasma homocysteine is an established cardiovascular disease risk factor. Recent studies show that exposure to particulate air pollution is associated with plasma homocysteine levels in adults but no studies on the association between prenatal air pollution and neonatal homocysteine levels exist. METHODS: In 609 newborns of the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we investigated the association between prenatal particulate matter exposure with a diameter ≤ 2.5 µm (PM2.5) and cord plasma homocysteine levels, and in a subset (n = 490) we studied the interaction with 11 single nucleotide polymorphism (SNPs) in oxidative stress-related genes (CAT, COMT, GSTP1, SOD2, NQO1 and HFE), through multiple linear regression. PM2.5 levels were obtained using a high resolution spatial temporal interpolation method. Homocysteine levels were measured by the homocysteine enzymatic assay on a Roche/Hitachi cobas c system. SNPs were assessed on the Biotrove OpenArray SNP genotyping platform. RESULTS: In multivariable-adjusted models, cord plasma homocysteine levels were 8.1% higher (95% CI: 1.9 to 14.3%; p = 0.01) for each 5 µg/m³ increment in average PM2.5 exposure during the entire pregnancy. With regard to pregnancy trimesters, there was only an association in the 2nd trimester: 3.6% (95% CI: 0.9% to 6.4%; p = 0.01). The positive association between PM2.5 in and homocysteine was (borderline) statistically significantly modified by genetic variants in MnSOD (p interaction = 0.02), GSTP1 (p interaction = 0.07) and the sum score of the 3 studied SNPs in the CAT gene (p interaction=0.09), suggesting oxidative stress as an underlying mechanism of action. CONCLUSIONS: Exposure to particulate air pollution in utero is associated with higher cord blood homocysteine levels, possibly through generating oxidative stress. Increased air pollution-induced homocysteine levels in early life might predispose for cardiovascular and other diseases later in life.

Children's Urinary Environmental Carbon Load. A Novel Marker Reflecting Residential Ambient Air Pollution Exposure?

RATIONALE: Ambient air pollution, including black carbon, entails a serious public health risk because of its carcinogenic potential and as climate pollutant. To date, an internal exposure marker for black carbon particles that have cleared from the systemic circulation into the urine does not exist. OBJECTIVES: To develop and validate a novel method to measure black carbon particles in a label-free way in urine. METHODS: We detected urinary carbon load in 289 children (aged 9-12 yr) using white-light generation under femtosecond pulsed laser illumination. Children's residential black carbon concentrations were estimated based on a high-resolution spatial temporal interpolation method. MEASUREMENTS AND MAIN RESULTS: We were able to detect urinary black carbon in all children, with an overall average (SD) of 98.2 × 105 (29.8 × 105) particles/ml. The urinary black carbon load was positively associated with medium-term to chronic (1 mo or more) residential black carbon exposure: +5.33 × 105 particles/ml higher carbon load (95% confidence interval, 1.56 × 105 to 9.10 × 105 particles/ml) for an interquartile range increment in annual residential black carbon exposure. Consistently, children who lived closer to a major road (≤160 m) had higher urinary black carbon load (6.93 × 105 particles/ml; 95% confidence interval, 0.77 × 105 to 13.1 × 105). CONCLUSIONS: Urinary black carbon mirrors the accumulation of medium-term to chronic exposure to combustion-related air pollution. This specific biomarker reflects internal systemic black carbon particles cleared from the circulation into the urine, allowing investigators to unravel the complexity of particulate-related health effects.

Newborn sex-specific transcriptome signatures and gestational exposure to fine particles: findings from the ENVIRONAGE birth cohort.

BACKGROUND: Air pollution exposure during pregnancy has been associated with adverse birth outcomes and health problems later in life. We investigated sex-specific transcriptomic responses to gestational long- and short-term exposure to particulate matter with a diameter < 2.5 µm (PM2.5) in order to elucidate potential underlying mechanisms of action. METHODS: Whole genome gene expression was investigated in cord blood of 142 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. Daily PM2.5 exposure levels were calculated for each mother's home address using a spatial-temporal interpolation model in combination with a dispersion model to estimate both long- (annual average before delivery) and short- (last month of pregnancy) term exposure. We explored the association between gene expression levels and PM2.5 exposure, and identified modulated pathways by overrepresentation analysis and gene set enrichment analysis. RESULTS: Some processes were altered in both sexes for long- (e.g. DNA damage) or short-term exposure (e.g. olfactory signaling). For long-term exposure in boys neurodevelopment and RhoA pathways were modulated, while in girls defensin expression was down-regulated. For short-term exposure we identified pathways related to synaptic transmission and mitochondrial function (boys) and immune response (girls). CONCLUSIONS: This is the first whole genome gene expression study in cord blood to identify sex-specific pathways altered by PM2.5. The identified transcriptome pathways could provide new molecular insights as to the interaction pattern of early life PM2.5 exposure with the biological development of the fetus.

Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure.

BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM10 exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM10 exposure. Overrepresentation analyses (ConsensusPathDB) were performed to identify enriched mitochondrial associated pathways and gene ontology sets. Thirteen Human MitoCarta genes were measured by means of quantitative real-time polymerase chain reaction (qPCR) along with mitochondrial DNA (mtDNA) content in an independent validation cohort (n = 169, 55.6% women). RESULTS: Overrepresentation analyses revealed significant pathways (p-value <0.05) related to mitochondrial genome maintenance and apoptosis for short-term exposure and to the electron transport chain (ETC) for medium-term exposure in women. For men, medium-term PM10 exposure was associated with the Tri Carbonic Acid cycle. In an independent study population, we validated several ETC genes, including UQCRH and COX7C (q-value <0.05), and some genes crucial for the maintenance of the mitochondrial genome, including LONP1 (q-value: 0.07) and POLG (q-value: 0.04) in women. CONCLUSIONS: In this exploratory study, we identified mitochondrial genes and pathways associated with particulate air pollution indicating upregulation of energy producing pathways as a potential mechanism to compensate for PM-induced mitochondrial damage.

Placental Nitrosative Stress and Exposure to Ambient Air Pollution During Gestation: A Population Study.

The placenta plays a crucial role in fetal growth and development through adaptive responses to perturbations of the maternal environment. We investigated the association between placental 3-nitrotyrosine (3-NTp), a biomarker of oxidative stress, and exposure to air pollutants during various time windows of pregnancy. We measured the placental 3-NTp levels of 330 mother-newborn pairs enrolled in the Environmental Influence on Ageing in Early Life (ENVIRONAGE) Study, a Belgian birth cohort study (2010-2013). Daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), black carbon (BC), and nitrogen dioxide were interpolated for each mother's residence using a spatiotemporal interpolation method. Placental 3-NTp levels, adjusted for covariates, increased by 35.0% (95% confidence interval (CI): 13.9, 60.0) for each interquartile-range increment in entire-pregnancy PM2.5 exposure. The corresponding estimate for BC exposure was 13.9% (95% CI: -0.21, 29.9). These results were driven by the first (PM2.5: 29.0% (95% CI: 4.9, 58.6); BC: 23.6% (95% CI: 4.4, 46.4)) and second (PM2.5: 39.3% (95% CI: 12.3, 72.7)) gestational exposure windows. This link between placental nitrosative stress and exposure to fine particle air pollution during gestation is in line with experimental evidence on cigarette smoke and diesel exhaust exposure. Further research is needed to elucidate potential health consequences experienced later in life through particle-mediated nitrosative stress incurred during fetal life.

Mitochondrial oxidative DNA damage and exposure to particulate air pollution in mother-newborn pairs.

BACKGROUND: Studies emphasize the importance of particulate matter (PM) in the formation of reactive oxygen species and inflammation. We hypothesized that PM exposure during different time windows in pregnancy influences mitochondrial 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, which is an established biomarker for oxidative stress, in both maternal and foetal blood. METHODS: We investigated maternal (n = 224) and cord blood (n = 293) from mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mitochondrial 8-OHdG by quantitative polymerase chain reaction (qPCR). Multivariable regression models were used to assess the association between mitochondrial 8-OHdG with PM10 and PM2.5 exposure over various time windows during pregnancy. RESULTS: In multivariable analysis, PM10 exposure during the entire pregnancy was positively associated with levels of mitochondrial 8-OHdG in maternal blood. For an IQR increment in PM10 exposure an increase of 18.3 % (95 % confidence interval (CI): 5.6 to 33.4 %, p = 0.004) in 8-OHdG was observed. PM10 exposure during the last trimester of pregnancy was positively associated with levels of 8-OHdG (28.1, 95 % CI: 8.6 to 51.2 %, p = 0.004, for an IQR increment in PM10). In a similar way, PM2.5 exposure was significantly associated with an increase of mitochondrial 8-OHdG levels in maternal blood during the entire pregnancy (13.9, 95 % CI: 0.4 to 29.4 %, p = 0.04 for an IQR increment in PM2.5 exposure) and third trimester of pregnancy (28.1, 95 % CI: 3.6 to 58.4 %, p = 0.02 for an IQR increment in PM2.5 exposure). In umbilical cord blood, 8-OHdG levels were significantly associated with PM10 exposure during first and second trimester of pregnancy with respectively an increase of 23.0 % (95 % CI: 5.9 to 42.8 %, p = 0.007) and 16.6 % (95 % CI: 1.8 to 33.5 %, p = 0.03) for an IQR increment in PM10 exposure. CONCLUSIONS: We found PM-associated increased mitochondrial oxidative DNA damage during pregnancy in both mothers and their newborns. Accordingly, our study showed that particulate air pollution exposure in early life plays a role in increasing systemic oxidative stress, at the level of the mitochondria, both in mother and foetus.

Recent exposure to ultrafine particles in school children alters miR-222 expression in the extracellular fraction of saliva.

BACKGROUND: Ultrafine particles (<100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children. This study examined whether exposure to fine and ultrafine particulate matter (PM) is associated with changes in the extracellular content of miR-222 and miR-146a of children. METHODS: Saliva was collected from 80 children at two different time points, circa 11 weeks apart and stabilized for RNA preservation. The extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We regressed the extracellular miRNA expression against recent exposure to ultrafine and fine particles measured at the school site using mixed models, while accounting for sex, age, BMI, passive smoking, maternal education, hours of television use, time of the day and day of the week. RESULTS: Exposure to ultrafine particles (UFP) at the school site was positively associated with miR-222 expression in the extracellular fraction in saliva. For each IQR increase in particles in the class room (+8504 particles/cm(3)) or playground (+28776 particles/cm(3)), miR-222 was, respectively 23.5 % (95 % CI: 3.5 %-41.1 %; p = 0.021) or 29.9 % (95 % CI:10.6 %-49.1 %; p = 0.0027) higher. No associations were found between miR-146a and recent exposure to fine and ultrafine particles. CONCLUSIONS: Our results suggest a possible epigenetic mechanism via which cells respond rapidly to small particles, as exemplified by miR-222 changes in the extracellular fraction of saliva.

Dynamic assessment of exposure to air pollution using mobile phone data.

BACKGROUND: Exposure to air pollution can have major health impacts, such as respiratory and cardiovascular diseases. Traditionally, only the air pollution concentration at the home location is taken into account in health impact assessments and epidemiological studies. Neglecting individual travel patterns can lead to a bias in air pollution exposure assessments. METHODS: In this work, we present a novel approach to calculate the daily exposure to air pollution using mobile phone data of approximately 5 million mobile phone users living in Belgium. At present, this data is collected and stored by telecom operators mainly for management of the mobile network. Yet it represents a major source of information in the study of human mobility. We calculate the exposure to NO2 using two approaches: assuming people stay at home the entire day (traditional static approach), and incorporating individual travel patterns using their location inferred from their use of the mobile phone network (dynamic approach). RESULTS: The mean exposure to NO2 increases with 1.27 µg/m(3) (4.3%) during the week and with 0.12 µg/m(3) (0.4%) during the weekend when incorporating individual travel patterns. During the week, mostly people living in municipalities surrounding larger cities experience the highest increase in NO2 exposure when incorporating their travel patterns, probably because most of them work in these larger cities with higher NO2 concentrations. CONCLUSIONS: It is relevant for health impact assessments and epidemiological studies to incorporate individual travel patterns in estimating air pollution exposure. Mobile phone data is a promising data source to determine individual travel patterns, because of the advantages (e.g. low costs, large sample size, passive data collection) compared to travel surveys, GPS, and smartphone data (i.e. data captured by applications on smartphones).

Environmental impact assessment and monetary ecosystem service valuation of an ecosystem under different future environmental change and management scenarios; a case study of a Scots pine forest.

For a sustainable future, we must sustainably manage not only the human/industrial system but also ecosystems. To achieve the latter goal, we need to predict the responses of ecosystems and their provided services to management practices under changing environmental conditions via ecosystem models and use tools to compare the estimated provided services between the different scenarios. However, scientific articles have covered a limited amount of estimated ecosystem services and have used tools to aggregate services that contain a significant amount of subjective aspects and that represent the final result in a non-tangible unit such as 'points'. To resolve these matters, this study quantifies the environmental impact (on human health, natural systems and natural resources) in physical units and uses an ecosystem service valuation based on monetary values (including ecosystem disservices with associated negative monetary values). More specifically, the paper also focuses on the assessment of ecosystem services related to pollutant removal/generation flows, accounting for the inflow of eutrophying nitrogen (N) when assessing the effect of N leached to groundwater. Regarding water use/provisioning, evapotranspiration is alternatively considered a disservice because it implies a loss of (potential) groundwater. These approaches and improvements, relevant to all ecosystems, are demonstrated using a Scots pine stand from 2010 to 2089 for a combination of three environmental change and three management scenarios. The environmental change scenarios considered interannual climate variability trends and included alterations in temperature, precipitation, nitrogen deposition, wind speed, Particulate matter (PM) concentration and CO2 concentration. The addressed flows/ecosystem services, including disservices, are as follows: particulate matter removal, freshwater loss, CO2 sequestration, wood production, NOx emissions, NH3 uptake and nitrogen pollution/removal. The monetary ecosystem service valuation yields a total average estimate of 361-1242 euro ha(-1) yr(-1). PM2.5 (<2.5 µm) removal is the key service, with a projected value of 622-1172 euro ha(-1) yr(-1). Concerning environmental impact assessment, with net CO2 uptake being the most relevant contributing flow, a loss prevention of 0.014-0.029 healthy life years ha(-1) yr(-1) is calculated for the respective flows. Both assessment methods favor the use of the least intensive management scenario due to its resulting higher CO2 sequestration and PM removal, which are the most important services of the considered ones.