Esmée Bijnens

In Utero Fine Particle Air Pollution and Placental Expression of Genes in the Brain-Derived Neurotrophic Factor Signaling Pathway: An ENVIRONAGE Birth Cohort Study.

Background Developmental processes in the placenta and the fetal brain are shaped by the same biological signals. Recent evidence suggests that adaptive responses of the placenta to the maternal environment may influence central nervous system development. Objectives We studied the association between in utero exposure to fine particle air pollution with a diameter ≤ 2.5 μm (PM2.5) and placental expression of genes implicated in neural development. Methods Expression of 10 target genes in the brain-derived neurotrophic factor (BDNF) signaling pathway were quantified in placental tissue of 90 mother–infant pairs from the ENVIRONAGE birth cohort using quantitative real-time polymerase chain reaction. Trimester-specific PM2.5 exposure levels were estimated for each mother’s home address using a spatiotemporal model. Mixed-effects models were used to evaluate the association between the target genes and PM2.5 exposure measured in different time windows of pregnancy. Results A 5-μg/m3 increase in residential PM2.5 exposure during the first trimester of pregnancy was associated with a 15.9% decrease [95% confidence interval (CI): –28.7, –3.2%, p = 0.015] in expression of placental BDNF at birth. The corresponding estimate for synapsin 1 (SYN1) was a 24.3% decrease (95% CI: –42.8, –5.8%, p = 0.011). Conclusions Placental expression of BDNF and SYN1, two genes implicated in normal neurodevelopmental trajectories, decreased with increasing in utero exposure to PM2.5. Future studies are needed to confirm our findings and evaluate the potential relevance of associations between PM2.5 and placental expression of BDNF and SYN1 on neurodevelopment. We provide the first molecular epidemiological evidence concerning associations between in utero fine particle air pollution exposure and the expression of genes that may influence neurodevelopmental processes. Citation Saenen ND, Plusquin M, Bijnens E, Janssen BG, Gyselaers W, Cox B, Fierens F, Molenberghs G, Penders J, Vrijens K, De Boever P, Nawrot TS. 2015. In utero fine particle air pollution and placental expression of genes in the brain-derived neurotrophic factor signaling pathway: an ENVIRONAGE Birth Cohort Study. Environ Health Perspect 123:834–840; http://dx.doi.org/10.1289/ehp.1408549

Neurobehavioral performance in adolescents is inversely associated with traffic exposure

On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: -0.02 to -0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function.

Lower placental telomere length may be attributed to maternal residential traffic exposure; a twin study

BACKGROUND High variation in telomere length between individuals is already present before birth and is as wide among newborns as in adults. Environmental exposures likely have an impact on this observation, but remain largely unidentified. We hypothesize that placental telomere length in twins is associated with residential traffic exposure, an important environmental source of free radicals that might accelerate aging. Next, we intend to unravel the nature-nurture contribution to placental telomere length by estimating the heritability of placental telomere length. METHODS We measured the telomere length in placental tissues of 211 twins in the East Flanders Prospective Twin Survey. Maternal traffic exposure was determined using a geographic information system. Additionally, we estimated the relative importance of genetic and environmental sources of variance. RESULTS In this twin study, a variation in telomere length in the placental tissue was mainly determined by the common environment. Maternal residential proximity to a major road was associated with placental telomere length: a doubling in the distance to the nearest major road was associated with a 5.32% (95% CI: 1.90 to 8.86%; p=0.003) longer placental telomere length at birth. In addition, an interquartile increase (22%) in maternal residential surrounding greenness (5 km buffer) was associated with an increase of 3.62% (95% CI: 0.20 to 7.15%; p=0.04) in placental telomere length. CONCLUSIONS In conclusion, we showed that maternal residential proximity to traffic and lower residential surrounding greenness is associated with shorter placental telomere length at birth. This may explain a significant proportion of air pollution-related adverse health outcomes starting from early life, since shortened telomeres accelerate the progression of many diseases.

Cohort Profile: The ENVIRonmental influence ON early AGEing (ENVIRONAGE): a birth cohort study

The ENVIRONAGE birth cohort is supported by the European Research Council [ERC-2012-StG.310898], and by funds of the Flemish Scientific Research council [FWO, G.0.733.15.N]. Bianca Cox, Janneke Hogervorst and Karen Vrijens have a postdoctoral fellowship from the Research Foundation - Flanders (FWO).

Impact of traffic related air pollution indicators on non-cystic fibrosis bronchiectasis mortality: a cohort analysis.

BackgroundMortality in non-cystic fibrosis bronchiectasis (NCFB) is known to be influenced by a number of factors such as gender, age, smoking history and Pseudomonas aeruginosa, but the impact of traffic related air pollution indicators on NCFB mortality is unknown.MethodsWe followed 183 patients aged 18 to 65 years with a HRCT proven diagnosis of NCFB and typical symptoms, who had visited the outpatient clinic at the University Hospital of Leuven, Belgium, between June 2006 and October 2012. We estimated hazard ratios (HR) for mortality in relation to proximity of the home to major roads and traffic load, adjusting for relevant covariables (age, gender, disease severity, chronic macrolide use, smoking history, socioeconomic status and Pseudomonas aeruginosa colonization status).ResultsFifteen out of the 183 included patients died during the observation period. Residential proximity to a major road was associated with the risk of dying with a HR 0.28 (CI 95% 0.10-0.77; p = 0.013) for a tenfold increase in distance to a major road. Mortality was also associated with distance-weighted traffic density within 100 meters (HR for each tenfold increase in traffic density 3.80; CI 95% 1.07-13.51; p = 0.04) and 200 meters from the patient’s home address (HR for each tenfold increase in traffic density 4.14; CI 95% 1.13-15.22; p = 0.032).ConclusionTraffic-related air pollution appears to increase the risk of dying in patients with NCFB.Trial registrationThe study was approved by the local ethical committee of the UZ Leuven, Belgium (ML-5028), registered at ClinicalTrial.gov (http://clinicaltrials.gov/show/NCT01906047).

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway. After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000–1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200–1000 and 100–500 m, respectively (hazard ratio 1.085– 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations. Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides. Long-term residential air pollution/traffic exposure associated with CLAD and survival after lung transplantation http://ow.ly/Izxj304uA5k

Mortality related to cold and heat. What do we learn from dairy cattle

Extreme temperatures are associated with increased mortality among humans. Because similar epidemiologic studies in animals may add to the existing evidence, we investigated the association between ambient temperature and the risk of mortality among dairy cattle. We used data on 87,108 dairy cow deaths in Belgium from 2006 to 2009, and we combined a case-crossover design with distributed lag non-linear models. Province-specific results were combined in a multivariate meta-analysis. Relative to the estimated minimum mortality temperature of 15.4°C (75th percentile), the pooled cumulative relative risks over lag 0-25 days were 1.26 (95% CI: 1.11, 1.42) for extreme cold (1st percentile, -3.5°C), 1.35 (95% CI: 1.19, 1.54) for moderate cold (5th percentile, -0.3°C), 1.09 (95% CI: 1.02, 1.17) for moderate heat (95th percentile, 19.7°C), and 1.26 (95% CI: 1.08; 1.48) for extreme heat (99th percentile, 22.6°C). The temporal pattern of the temperature-mortality association was similar to that observed in humans, i.e. acute effects of heat and delayed and prolonged effects of cold. Seasonal analyses suggested that most of the temperature-related mortality, including cold effects, occurred in the warm season. Our study reinforces the evidence on the plausibility of causal effects in humans.

Left ventricular function in relation to chronic residential air pollution in a general population

Background In view of the increasing heart failure epidemic and awareness of the adverse impact of environmental pollution on human health, we investigated the association of left ventricular structure and function with air pollutants in a general population. Methods In 671 randomly recruited Flemish (51.7% women; mean age, 50.4 years) we echocardiographically assessed left ventricular systolic strain and strain rate and the early and late peak velocities of transmitral blood flow and mitral annular movement (2005−2009). Using subject-level data, left ventricular function was cross-sectionally correlated with residential long-term exposure to air pollutants, including black carbon, PM2.5, PM10 (particulate matter) and nitrogen dioxide (NO2), while accounting for clustering by residential address and confounders. Results Annual exposures to black carbon, PM2.5, PM10 and NO2 averaged 1.19, 13.0, 17.7, and 16.8 µg/m3. Systolic left ventricular function was worse (p ≤ 0.027) with higher black carbon, PM2.5, PM10 and NO2 with association sizes per interquartile interval increment ranging from −0.339 to −0.458% for longitudinal strain and from −0.033 to −0.049 s−1 for longitudinal strain rate. Mitral E and a′ peak velocities were lower (p ≤ 0.021) with higher black carbon, PM2.5 and PM10 with association sizes ranging from −1.727 to −1.947 cm/s and from −0.175 to −0.235 cm/s, respectively. In the geographic analysis, the systolic longitudinal strain sided with gradients in air pollution. The path analysis identified systemic inflammation as a possible mediator of associations with black carbon. Conclusions Long-term low-level air pollution is associated with subclinical impairment of left ventricular performance and might be a risk factor for heart failure.

Small for gestational age and exposure to particulate air pollution in the early-life environment of twins

Several studies in singletons have shown that maternal exposure to ambient air pollutants is associated with restricted fetal growth. About half of twins have low birth weight compared with six percent in singletons. So far, no studies have investigated maternal air pollution exposure in association with birth weight and small for gestational age in twins. We examined 4760 twins of the East Flanders Prospective Twins Survey (2002-2013), to study the association between in utero exposure to air pollution with birth weight and small for gestational age. Maternal particulate air pollution (PM10) and nitric dioxide (NO2) exposure was estimated using a spatial temporal interpolation method over various time windows during pregnancy. In the total group of twins, we observed that higher PM10 and NO2 exposure during the third trimester was significantly associated with a lower birth weight and higher risk of small for gestational age. However, the association was driven by moderate to late preterm twins (32-36 weeks of gestation). In these twins born between 32 and 36 weeks of gestation, birth weight decreased by 40.2g (95% CI: -69.0 to -11.3; p=0.006) and by 27.3g (95% CI: -52.9 to -1.7; p=0.04) in association for each 10µg/m³ increment in PM10 and NO2 concentration during the third trimester. The corresponding odds ratio for small for gestational age were 1.68 (95% CI: 1.27-2.33; p=0.0003) and 1.51 (95% CI: 1.18-1.95; p=0.001) for PM10 or NO2, respectively. No associations between air pollution and birth weight or small for gestational age were observed among term born twins. Finally, in all twins, we found that for each 10µg/m³ increase in PM10 during the last month of pregnancy the within-pair birth weight difference increased by 19.6g (95% CI: 3.7-35.4; p=0.02). Assuming causality, an achievement of a 10µg/m³ decrease of particulate air pollution may account for a reduction by 40% in small for gestational age, in twins born moderate to late preterm.

Cord plasma insulin and in utero exposure to ambient air pollution

INTRODUCTION Cardio-metabolic risk factors including insulin levels are at young age barely perceived as harmful, but over time these risk factors may track and lead to higher risk of metabolic syndrome. Studies showed that exposure to air pollution is associated with an increased risk of insulin resistance in childhood. We determined whether the origin of type 2 diabetes can be found in the early childhood by examining the levels of insulin in the neonatal cord blood and whether this can be considered as a disease marker for later life. METHODS In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we recruited 620 mother-infant pairs between February 2nd 2010 until August 12th 2014 at the East-Limburg Hospital in Genk, Belgium. We investigated in 590 newborns the association between cord plasma insulin levels and exposure to particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) in various exposure windows during pregnancy. Trimester-specific air pollutant exposure levels were estimated for each mothers home address using a spatiotemporal model. RESULTS Cord plasma insulin levels averaged 33.1pmol/L (25-75th percentile: 20.1-53.5), while PM2.5 exposure during pregnancy averaged (SD) 13.7μg/m3 (2.4). Independent of maternal age, newborns sex, birth weight, gestational age, parity, early-pregnancy BMI, ethnicity, smoking status, time of the day, maternal education, time of delivery, and season of delivery, cord plasma insulin levels increased with 15.8% (95% CI 7.8 to 24.4, p<0.0001) for each SD increment in PM2.5 levels during the entire pregnancy and was most pronounced in the 2nd trimester (13.1%, 95% CI 3.4 to 23.7, p=0.007) of pregnancy. The results for PM10 exposure were similar with those of PM2.5 exposure but we did not observe an association between cord blood insulin levels and NO2 exposure. CONCLUSIONS Exposure to particulate air pollution during pregnancy is associated with increased levels of cord plasma insulin at birth. The public health relevance of this association is demonstrated by the fact that a 2.4μg/m3 (SD) increase in PM2.5 during pregnancy on cord plasma insulin levels corresponds to the effect-size of a 9kg/m2 higher early-pregnancy BMI on cord plasma. Particulate air pollution induced changes in cord plasma insulin levels during early life and might be a risk factor in the development of metabolic disease, such as glucose intolerance or type 2 diabetes, later in life.