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The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho

Exposure to air pollution influences children's health, however, the biological mechanisms underlying these effects are not completely elucidated. We investigated the association between short- and medium-term outdoor air pollution exposure with protein profiles and their link with blood pressure in 1170 HELIX children aged 6-11 years. Different air pollutants (NO2, PM10, PM2.5, and PM2.5abs) were estimated based on residential and school addresses at three different windows of exposure (1-day, 1-week, and 1-year before clinical and molecular assessment). Thirty-six proteins, including adipokines, cytokines, or apolipoproteins, were measured in children's plasma using Luminex. Systolic and diastolic blood pressure (SBP and DBP) were measured following a standardized protocol. We performed an association study for each air pollutant at each location and time window and each outcome, adjusting for potential confounders. After correcting for multiple-testing, hepatocyte growth factor (HGF) and interleukin 8 (IL8) levels were positively associated with 1-week home exposure to some of the pollutants (NO2, PM10, or PM2.5). NO2 1-week home exposure was also related to higher SBP. The mediation study suggested that HGF could explain 19% of the short-term effect of NO2 on blood pressure, but other study designs are needed to prove the causal directionality between HGF and blood pressure. The study received funding from the European Community’s Seventh Framework Programme (FP7/2007–206) (grant agreement no 308333) (HELIX project), the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project) and from the European Union’s Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)). BiB received funding from the Welcome Trust (WT101597MA), from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/ 1). The study was supported by the European Union FP7 programmes (FP7/ 2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects). INMA was supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV. 2007.1.2.2.2. Project No 211250 Escape, EU FP7- 2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV. 2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX). MC received funding from Instituto Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128). JU is supported by Spanish regional program PERIS (Ref.: SLT017/20/ 000119) Granted by Departament de Salut de la Generalitat de Catalunya. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII)

Background: Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. Objectives: Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. Methods: The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. Results: The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. Discussion: This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975. This study received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 308333 – the HELIX project for data collection and analyses. The HELIX program built on six existing cohorts that received previous funding, including the major ones listed below. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, National Institutes of Health (NIH)/ National Institute of Environmental Health Sciences (NIEHS) (contract no. N01-ES-75558), and NIH/NINDS (grants 1 UO1 NS 047537-01 and 2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus,” Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). M.C. received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). L.C. was supported by the NIH/NIEHS grants R21ES029681, R01ES030691, R01ES029944, R01 ES030364, R21ES028903, and P30ES007048.

We investigated the association between daily emergency ambulance calls (EAC) for elevated blood pressure that occurred during the time intervals of 8:00-13:59, 14:00-21:59, and 22:00-7:59, and exposure to CO, PM

A circadian variation in the cardiovascular parameters has been detected. It is plausible that the influence of the environment varies during different periods of the day. We investigated the association between daily emergency ambulance calls (EC) for paroxysmal atrial fibrillation (AF) that occurred during the time intervals of 8:00-13:59, 14:00-21:59, and 22:00-7:59, and weather conditions and exposure to CO and PM10. We used Poisson regression to explore the association between the risk of EC for AF and environmental variables, adjusting for seasonal variation. Before noon, the risk was associated with an IQR (0.333 mg/m3) increase in CO at lag 2-6 days above the median (RR = 1.15, P = 0.002); a protective impact of CO on previous day was observed (RR = 0.91, P = 0.018). During 14:00-21:59, a negative effect of air temperature below 1.9 °C (lag 2-3 days) was detected (per 10 °C decrease: RR = 1.17, P = 0.044). At night, the elevated risk was associated with wind speed above the median (lag 2-4 days) (per 1-kt increase: RR = 1.07, P = 0.001) and with PM10 at lag 2-5 days below the median (per IQR (7.31 μg/m3) increase: RR = 1.21, P = 0.002). Individuals over 65 years of age were more sensitive to air pollution, especially at night (CO lag 2-3 days

Background Physical activity (PA) influences people’s individual health and quality of life and contributes to prevent non-communicable diseases. Research shows that only one third of the EU inhabitants satisfy the World Health Organisation’s recommendations for PA levels. Global decline in PA levels is associated with economic development, an increase in urbanization, communication technologies and the use of passive modes of transport. The aim of the study was to assess the levels of PA depending on socioeconomic factors and health among adults. Methods A cross sectional study of a random sample of Kaunas residents was conducted to investigate the habits of PA. A representative sample of 1111 individuals who completed the questionnaire were included in the study. Validated questionnaires were used to collect data. Multivariate logistic regressions were used to assess the relationship between the levels of PA and socioeconomic factors and health, adjusting for confounders. Results Our findings showed that non-workers were three times (OR 3.16; 95% CI 1.23-8.13) more likely to reach the levels of recommended PA compared to workers. The results revealed that car disposal and the increase in body mass index (BMI) were the two most important factors that reduced odds of reaching recommended levels of PA by 64 % (OR 0.36; 95% CI 0.14-0.93) and 13 % (OR 0.87; 95% CI 0.80-0.96). Conclusions The differences in PA levels by individual socioeconomic factors and health were investigated in this study. The European Commission actively promotes Sustainable Urban Mobility Planning by developing guidelines for the local authorities to promote active mobility and increase PA. Key messages The study highlights the importance of considering different individual characteristics when assessing PA and evaluating related health effects. It is important to improve the accessibility of urban areas and create cleaner and more sustainable transport modes to increase PA.

Background According to the World Health Organization, non-communicable diseases or chronic diseases, account for 71 percent of all deaths globally, affecting individuals of all age groups and countries. Epidemiological studies have shown an association between a lack of physical activity (PA) and the risk of raised blood pressure, increased body mass index and obesity that can lead to chronic diseases. Methods The aim of the study was to assess the relationship between leisure-time PA and the risk of chronic diseases among adult population. We conducted a cross-sectional study of 470 men and 641 women who participated in “The Impact of Sustainable Mobility, Physical Activity and Environmental Factors on Urban Population Health Study (ISMA)” in Lithuania. Leisure-time PA was self-reported and divided into three levels: low, moderate and high. Logistic regression was used to estimate adjusted odds ratios (ORs) of chronic diseases according to leisure-time PA. Results More than half (55%) of the study population engaged in a moderate intensity PA and 12% of participants engaged in a high intensity leisure-time PA. Men 1.6 times more often than women reported engaging in a high intensity PA in leisure time (p = 0.004). Adults who engaged in low intensity leisure-time PA had almost 3 times (OR = 2.91; 95% confidence interval (CI) 1.62-5.24) higher risk of chronic diseases, whereas those adults who reported moderate intensity leisure-time PA had an OR of 1.63 (95% CI 0.92-2.87) compared to individuals who engaged in a high-level PA. Conclusions Our findings suggest that high levels of leisure-time PA could reduce the risk of chronic diseases and this effect was significantly stronger in men. Key messages Global decline in PA is related to inaction during leisure time and sedentary behaviour at work and at home that has a major health impact worldwide. High levels of leisure-time PA are important factor for chronic disease prevention.

Aim The aim of this study was to determine the association between levels of residential surrounding greenness, preschool children's park use, sedentary behaviour, and mental and general health. Methods This cross-sectional study included 1489 4-6-year-old children – residents of Kaunas city, Lithuania. Responses to the questionnaires completed by parents were used to ascertain children's general and mental health. We estimated exposure to greenness by the normalised difference vegetation index (NDVI), and time spent in a park (i.e. park use). We used multivariate logistic regression models to explore the independent associations between health outcomes and surrounding greenness and time spent in the nearest city park, controlling for potential confounders. Results Of all the studied children, 14% had poor perceived general health, and 44.7% spent 5 or more hours per week in city parks. A significant increase in sedentary behaviour was observed in children with poor health. Every additional hour of time spent in parks was associated with decreased sedentary behaviour and a lower risk of poor health; meanwhile, lower residential greenness was associated with poorer mental and general health. Compared with NDVI-100 m > median and park use exceeding 5 h per week, lower greenness exposure and shorter park usage were associated with the risk of poor health (adjusted odds ratio 2.32 (95% CI: 1.43, 3.78) and the general risk of mental difficulties (adjusted odds ratio 1.43 (95% CI: 1.03, 2.18) in 4–6-year-old children. Conclusions Lower residential greenness levels and less time spent in a park were associated with poorer general and mental health among 4-6-year-old children. Physical activity in green spaces is recommended as a measure to prevent poor general and mental health among children.

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities. This work was supported by the European Commission Seventh Framework Programme (FP7/2007–2013) [grant number: 308333–the HELIX project]. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7-HEALTH-2012 Proposal No 308333 HELIX, FP7 European Union project, No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15).

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. Objective: We evaluated the association of the urban exposome with birth weight. Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures. Results: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis. Conclusion: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement No. 308333—the HELIX project—for data collection and analyses. The HELIX program built on six existing cohorts that received previous funding, including the major cohorts listed here. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, the Conselleria de Sanitat, Generalitat Valenciana, Department of Health of the Basque Government; the Provincial Government of Gipuzkoa, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). MoBa (Norwegian Mother and Child Cohort Study) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (Contract No. N01-ES-75558), and the U.S. National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS; Contract No. N01-ES-75558), and National Institute of Neurological Disorders and Stroke (Grant No. 1 UO1 NS 047537-01 and Grant No. 2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects (EU FP6–2003-Food-3-NewGeneris, EU FP6.STREP Hiwate, EU FP7 ENV.2007·1.2.2.2, Project No. 211250 Escape, EU FP7–2008-ENV-1·2.1·4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6, Proposal No. 226285 ENRIECO, EUFP7-HEALTH-2012 Proposal No. 308333 HELIX, FP7 European Union Project No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). L.C. received additional funding from the Southern California Environmental Health Sciences Center (Grant No. P30ES007048) funded by NIEHS. We acknowledge the support of the program for international scientific collaborations of Région Rhône-Alpes-Auvergne.

BACKGROUND Growing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously.OBJECTIVES This study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children.METHODS Systolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously.RESULTS Decreases in systolic BP were observed with facility density (beta change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono -benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]).CONCLUSIONS This study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children. (C) 2019 by the American College of Cardiology Foundation.

Background Metabolic syndrome (MS) is characterized by numerous metabolic risk factors. We investigated the associations between a long-term exposure to ambient air pollution and the residential distance to green spaces (GS) and major roads with the development of arterial hypertension (AH) and some components of MS. These associations were assessed among persons living in private and multi-story houses (MH). Methods We selected 1354 participants for the population study from MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease Program). The exposures to PM10, PM2.5, and NO2 levels were assessed by using the LUR models for Kaunas City. Results In the participants who lived in MH, the residential distance to a major road closer than 200 m and the residential exposure to PM10 and PM2.5 levels above the median were associated with a higher risk of AH (the adjusted relative risks (RRs), respectively, were 1.41(1.10–1.81), 1.19(1.01–1.42) and 1.27(1.07–1.52)). In these participants, the residential exposure to a PM10 level above the median was associated with a higher risk of reduced high density lipoprotein (RHDL) (RR = 1.46(1.05–2.05)). A negative impact of the traffic air pollutants on the incidence of AH, RHDL cholesterol and high triglyceride levels was observed only in the participants who lived in MH.