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Abstract Background Genetic susceptibility to tobacco smoke might modify the effect of smoking on pregnancy outcomes. Methods We conducted a case–control study of 543 women who delivered singleton live births in Kaunas (Lithuania), examining the association between low-level tobacco smoke exposure (mean: 4.8 cigarettes/day) during pregnancy, GSTT1 and GSTM1 polymorphisms and birthweight of the infant. Multiple linear-regression analysis was performed adjusting for gestational age, maternal education, family status, body mass index, blood pressure, and parity. Subsequently, we tested for the interaction effect of maternal smoking, GSTT1 and GSTM1 genes polymorphisms with birthweight by adding all the product terms in the regression models. Results The findings suggested a birthweight reduction among light-smoking with the GSTT1–null genotype (−162.9 g, P = 0.041) and those with the GSTM1–null genotype (−118.7 g, P = 0.069). When a combination of these genotypes was considered, birthweight was significantly lower for infants of smoking women the carriers of the double-null genotypes (−311.2 g, P = 0.008). The interaction effect of maternal smoking, GSTM1 and GSTT1 genotypes was marginally significant on birthweight (−234.5 g, P = 0.078). Among non-smokers, genotype did not independently confer an adverse effect on infant birthweight. Conclusions The study shows the GSTT1–null genotype, either presents only one or both with GSTM1–null genotype in a single subject, have a modifying effect on birthweight among smoking women even though their smoking is low level. Our data also indicate that identification of the group of susceptible subjects should be based on both environmental exposure and gene polymorphism. Findings of this study add additional evidence on the interplay among two key GST genes and maternal smoking on birth weight of newborns.

Abstract Background Recent reports have shown that air pollution may increase the risk of adverse birth outcomes. We have evaluated the relationship between ambient air pollution and the occurrence of low birth weight and preterm delivery using routinely collected data in Lithuania. Methods This epidemiological study comprised all singleton newborns (N = 3,988), born to women in 1998, who resided in the City of Kaunas. Birth data and information on maternal characteristics were obtained from the Lithuanian National Birth Register. To estimate residential exposure levels, we used measurements of ambient nitrogen dioxide (NO2) and formaldehyde, which were collected at 12 monitoring posts. Multivariate logistic regression was used to estimate the effect that each pollutant would have on low birth weight (LBW) and premature birth while controlling for potential confounders. Results Adjusted odds ratios (OR) for LBW increased with increasing formaldehyde exposure (OR2nd tertile = 1.86, 95% CI 1.10–3.16; OR3rd tertile = 1.84, 95% CI 1.12–3.03). Adjusted ORs of preterm birth for the medium and high NO2 tertile exposures were OR = 1.14 (95% CI 0.77–1.68) and OR = 1.68 (95% CI 1.15–2.46), respectively. The risk of preterm birth increased by 25% (adjusted OR = 1.25, 95% CI 1.07–1.46) per 10 μg/m3 increase in NO2 concentrations. An analysis by trimester showed that pregnancy outcomes were associated with first-trimester exposure to air pollutants. However, there were no significant relationships in other pregnancy periods between preterm birth and exposure to formaldehyde or between LBW and NO2 exposure. Conclusion Our findings suggest that in the City of Kaunas there might be a relationship between maternal exposure to ambient formaldehyde and the risk of LBW, as well as between NO2 exposure and the risk of preterm birth.

Background: Precision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g., environmental pollutants)., Objective: To develop and apply a precision health framework which combines multiomic integration (including early, intermediate, and late integration, representing sequential stages at which omics layers are combined for modeling) with mediation approaches (including high-dimensional mediation to identify biomarkers, mediation with latent factors to identify pathways, and integrated/quasi-mediation to identify high-risk subpopulations) to identify novel biomarkers of prenatal mercury induced metabolic dysfunction-associated fatty liver disease (MAFLD), elucidate molecular pathways linking prenatal mercury with MAFLD in children, and identify high-risk children based on integrated exposure and multiomics data., Methods: This prospective cohort study used data from 420 mother-child pairs from the Human Early Life Exposome (HELIX) project. Mercury concentrations were determined in maternal or cord blood from pregnancy. Cytokeratin 18 (CK-18; a MAFLD biomarker) and five omics layers (DNA Methylation, gene transcription, microRNA, proteins, and metabolites) were measured in blood in childhood (age 6-10 years)., Results: Each standard deviation increase in prenatal mercury was associated with a 0.11 [95% confidence interval: 0.02-0.21] standard deviation increase in CK-18. High dimensional mediation analysis identified 10 biomarkers linking prenatal mercury and CK-18, including six CpG sites and four transcripts. Mediation with latent factors identified molecular pathways linking mercury and MAFLD, including altered cytokine signaling and hepatic stellate cell activation. Integrated/quasi-mediation identified high risk subgroups of children based on unique combinations of exposure levels, omics profiles (driven by epigenetic markers), and MAFLD., Conclusions: Prenatal mercury exposure is associated with elevated liver enzymes in childhood, likely through alterations in DNA methylation and gene expression. Our analytic framework can be applied across many different fields and serve as a resource to help guide future precision health investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mercury has high industrial utility and is present in many products, and environmental contamination and occupational exposure are widespread. There are numerous biological systems involved in the absorption, metabolism, and excretion of Hg, and it is possible that some systems may be impacted by genetic variation. If so, genotype may affect tissue concentrations of Hg and subsequent toxic effects. Genome-wide association testing was performed on blood Hg samples from pregnant women of the Avon Longitudinal Study of Parents and Children ( n = 2893) and children of the Human Early Life Exposome ( n = 1042). Directly-genotyped single-nucleotide polymorphisms (SNPs) were imputed to the Haplotype Reference Consortium r1.1 panel of whole genotypes and modelled againstlog-transformed Hg. Heritability was estimated using linkage disequilibrium score regression. The heritability of Hg was estimated as 24.0% (95% CI: 16.9% to 46.4%) in pregnant women, but could not be determined in children. There were 16 SNPs associated with Hg in pregnant women above a suggestive p -value threshold ( p < 1 × 10 -5 ), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant ( p < 5 × 10 -8 ). SNP-Hg associations were highly discordant between women and children, and this may reflect differences in metabolism, a gene-age interaction, or dose-response effects. Several suggestive variants had plausible links to Hg metabolism, such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channel genes. The findings would benefit from external validation, as suggestive results may contain both true associations and false positives.

Green spaces may have beneficial impacts on children's cognition. However, few studies explored the exposure to green spaces beyond residential areas, and their availability, accessibility and uses at the same time. The aim of the present study was to describe patterns of availability, accessibility, and uses of green spaces among primary school children and to explore how these exposure dimensions are associated with cognitive development. Exposures to green space near home, school, commuting route, and other daily activity locations were assessed for 1607 children aged 6-11 years from six birth cohorts across Europe, and included variables related to: availability (NDVI buffers: 100, 300, 500 m), potential accessibility (proximity to a major green space: linear distance; within 300 m), and use (play time in green spaces: hours/year), and the number of visits to green spaces (times/previous week). Cognition measured as fluid intelligence, inattention, and working memory was assessed by computerized tests. We performed multiple linear regression analyses on pooled and imputed data adjusted for individual and area-level confounders. Availability, accessibility, and uses of green spaces showed a social gradient that was unfavorable in more vulnerable socioeconomic groups. NDVI was associated with more playing time in green spaces, but proximity to a major green space was not. Associations between green space exposures and cognitive function outcomes were not statistically significant in our overall study population. Stratification by socioeconomic variables showed that living within 300 m of a major green space was associated with improved working memory only in children in less deprived residential areas (β = 0.30, CI: 0.09,0.51), and that more time playing in green spaces was associated with better working memory only in children of highly educated mothers (β per IQR increase in hour/year = 0.10; 95% CI: 0.01, 0.19). However, studying within 300 m of a major green space increased inattention scores in children in more deprived areas (β = 15.45, 95% CI: 3.50, 27.40)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs., Methods: We used data from the HELIX Child Panel Study, which included 156 children aged 6 to 11. Children were followed for one week, in two time periods. Twenty-two non-persistent EDCs (10 phthalate, 7 phenol, and 5 organophosphate pesticide metabolites) were measured in two weekly pools of 15 urine samples each. Multi-omic profiles (methylome, serum and urinary metabolome, proteome) were measured in blood and in a pool urine samples. We developed visit-specific Gaussian Graphical Models based on pairwise partial correlations. The visit-specific networks were then merged to identify reproducible associations. Independent biological evidence was systematically sought to confirm some of these associations and assess their potential health implications., Results: 950 reproducible associations were found among which 23 were direct associations between EDCs and omics. For 9 of them, we were able to find corroborating evidence from previous literature: DEP - serotonin, OXBE - cg27466129, OXBE - dimethylamine, triclosan - leptin, triclosan - serotonin, MBzP - Neu5AC, MEHP - cg20080548, oh-MiNP - kynurenine, oxo-MiNP - 5-oxoproline. We used these associations to explore possible mechanisms between EDCs and health outcomes, and found links to health outcomes for 3 analytes: serotonin and kynurenine in relation to neuro-behavioural development, and leptin in relation to obesity and insulin resistance., Conclusions: This multi-omics network analysis at two time points identified biologically relevant molecular signatures related to non-persistent EDC exposure in childhood, suggesting pathways related to neurological and metabolic outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6-11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (-1.25; -2.10, -0.40), house crowding (-0.39; -0.62, -0.16), and child environmental tobacco smoke (ETS) (-0.89; -1.42, -0.35), were all associated with lower CPM scores. Indoor PM 2.5 exposure was associated with lower N-Back scores (-0.09; -0.16, -0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely and cross-sectionally associate with cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior., Methods and Findings: We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6-11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner's Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent's reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides., Conclusions: Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures., Objective: This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour., Methods: We studied 708 mother-child pairs from five European cohorts recruited in 2003-2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently., Results: LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations., Discussion: This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children., Approach and Results: We used data from 1,105 mothers and their children (median age, 8.2 years; interquartile range, 6.6-9.1) from the European Human Early-Life Exposome cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the United Kingdom). We measured concentrations of perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane sulfonate, and perfluoroundecanoate in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian kernel machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21-1.92) that was characterized by high prenatal exposure to PFAS and increased serum levels of branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (tryptophan and phenylalanine), and glycerophospholipids (phosphatidylcholine [PC] aa C36:1 and Lyso-PC a C18:1)., Conclusions: Developmental exposure to PFAS can contribute to pediatric liver injury., (© 2020 by the American Association for the Study of Liver Diseases.)

The perception of urban environmental quality is an important contributor when identifying local problems in sustainable development and environmental planning policy. This study examined the associations between environmental and social residential characteristics, physical activity, obesity, and hypertension in Kaunas city, Lithuania. This cross-sectional study analyzed 580 citizens' demographic-, socioeconomic-, health-, and lifestyle-related factors, environmental health concerns, and environmental quality perceptions. Using Geographic Information Systems and the multivariate logistic regression, we found that the less physically active group more often presented lower than mean ratings of the quality of pathways and cycling routes (32.9% and 45.6%, p = 0.042) and only irregularly visited the natural environment. Obese participants presented poorer ratings of air pollution, the quality of pathways and cycling routes, their possibility to reach green spaces by walking, and the available relaxing areas. The environmental issues associated with hypertension were poor possibilities to reach green spaces by walking (OR 1.94, 95% CI 1.14-3.32) and the availability of relaxation areas (OR 2.30, 95% 1.34-3.95). The quality of the neighborhood and individual-level characteristics were the factors that influenced a higher prevalence of health problems at the district level. Our findings suggest that a public health policy to improve the physical and social environment of the neighborhood would have a potential to increase citizens' physical activity and health.

Background: Despite the large number of studies on beneficial effects of the natural outdoor environment (NOE) on health, the underlying mechanisms are not fully understood., Objective: This study explored the relations between amount, quality, use and experience of the NOE; and physical activity, social contacts and mental well-being., Methods: In this cross-sectional study, data on GIS-derived measures of residential surrounding greenness (NDVI), NOE within 300 m, and audit data on quality of the streetscape were combined with questionnaire data from 3947 adults in four European cities. These included time spent in NOE (use); and perceived greenness, and satisfaction with and importance given to the NOE (experience). Physical activity, social contacts and mental health were selected as key outcome indicators. Descriptive and multilevel analyses were conducted both on pooled data and for individual cities., Results: More minutes spent in the NOE were associated with more minutes of physical activity, a higher frequency of social contacts with neighbors, and better mental well-being. Perceived greenness, satisfaction with and importance of the NOE, were other strong predictors of the outcomes, while GIS measures of NOE and streetscape quality were not. We found clear differences between the four cities., Conclusions: Use and experience of the natural outdoor environment are important predictors for beneficial effects of the natural outdoor environment and health. Future research should focus more on these aspects to further increase our understanding of these mechanisms, and needs to take the local context into account., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 (β 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., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Exposure assessment is an important part in environmental epidemiology for determining the associations of environmental factors with health effects. One of the greatest challenges for personal exposure assessment is associated with peoples' mobility during the day and spatial and temporal dynamics of air pollution. In this study, the impact of PM 10 (particulate matter less than 10 μm) on allergy risk among adults was assessed using objective methods of exposure assessment. The primary objective of the present study was to estimate personal exposure to PM 10 based on individual daily movement patterns. Significant differences between the concentration of PM 10 in different microenvironments (MEs) and personal exposure to PM 10 were determined. Home exposure accounted for the largest part of PM 10 exposure. Thirty-five percent of PM 10 exposure was received in other non-home MEs. Allergy risk increased significantly with increasing exposure to PM 10 . Adults exposed to the highest levels of PM 10 exposure had a twice-higher risk of allergies than adults exposed to the lowest levels of PM 10 exposure. The study results have practical relevance for exposure assessment to environmental factors and its impact on health effects.

Background : Environmental factors determine children's health. Quantifying the health impacts related to environmental hazards for children is essential to prioritize interventions to improve health in Europe. Objective : This study aimed to assess the burden of childhood disease due to environmental risks across the European Union. Methods : We conducted an environmental burden of childhood disease assessment in the 28 countries of the EU (EU28) for seven environmental risk factors (particulate matter less than 10 micrometer of diameter (PM 10 ) and less than 2.5 micrometer of diameter (PM 2.5 ), ozone, secondhand smoke, dampness, lead, and formaldehyde). The primary outcome was disability-adjusted life years (DALYs), assessed from exposure data provided by the World Health Organization, Global Burden of Disease project, scientific literature, and epidemiological risk estimates. Results : The seven studied environmental risk factors for children in the EU28 were responsible for around 211,000 DALYs annually. Particulate matter (PM 10 and PM 2.5 ) was the main environmental risk factor, producing 59% of total DALYs (125,000 DALYs), followed by secondhand smoke with 20% of all DALYs (42,500 DALYs), ozone 11% (24,000 DALYs), dampness 6% (13,000 DALYs), lead 3% (6200 DALYs), and formaldehyde 0.2% (423 DALYs). Conclusions : Environmental exposures included in this study were estimated to produce 211,000 DALYs each year in children in the EU28, representing 2.6% of all DALYs in children. Among the included environmental risk factors, air pollution (particulate matter and ozone) was estimated to produce the highest burden of disease in children in Europe, half of which was due to the effects of PM 10 on infant mortality. Effective policies to reduce environmental pollutants across Europe are needed.

Introduction: Better mental health has been associated with exposure to natural outdoor environments (NOE). However, comprehensive studies including several indicators of exposure and outcomes, potential effect modifiers and mediators are scarce., Objectives: We used novel, objective measures to explore the relationships between exposure to NOE (i.e. residential availability and contact) and different indicators of mental health, and possible modifiers and mediators., Methods: A nested cross-sectional study was conducted in: Barcelona, Spain; Stoke-on-Trent, United Kingdom; Doetinchem, Netherlands; Kaunas, Lithuania. Participants' exposure to NOE (including both surrounding greenness and green and/or blue spaces) was measured in terms of (a) amount in their residential environment (using Geographical Information Systems) and (b) their contact with NOE (using smartphone data collected over seven days). Self-reported information was collected for mental health (psychological wellbeing, sleep quality, vitality, and somatisation), and potential effect modifiers (gender, age, education level, and city) and mediators (perceived stress and social contacts), with additional objective NOE physical activity (potential mediator) derived from smartphone accelerometers., Results: Analysis of data from 406 participants showed no statistically significant associations linking mental health and residential NOE exposure. However, NOE contact, especially surrounding greenness, was statistically significantly tied to better mental health. There were indications that these relationships were stronger for males, younger people, low-medium educated, and Doetinchem residents. Perceived stress was a mediator of most associations, and physical activity and social contacts were not., Conclusions: Our findings indicate that contact with NOE benefits mental health. Our results also suggest that having contact with NOE that can facilitate stress reduction could be particularly beneficial., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study investigated whether residential availability of natural outdoor environments (NOE) was associated with contact with NOE, overall physical activity and physical activity in NOE, in four different European cities using objective measures. A nested cross-sectional study was conducted in Barcelona (Spain); Stoke-on-Trent (United Kingdom); Doetinchem (The Netherlands); and Kaunas (Lithuania). Smartphones were used to collect information on the location and physical activity (overall and NOE) of around 100 residents of each city over seven days. We used Geographic Information Systems (GIS) to determine residential NOE availability (presence/absence of NOE within 300 m buffer from residence), contact with NOE (time spent in NOE), overall PA (total physical activity), NOE PA (total physical activity in NOE). Potential effect modifiers were investigated. Participants spent around 40 min in NOE and 80 min doing overall PA daily, of which 11% was in NOE. Having residential NOE availability was consistently linked with higher NOE contact during weekdays, but not to overall PA. Having residential NOE availability was related to NOE PA, especially for our Barcelona participants, people that lived in a city with low NOE availability., Competing Interests: The authors declare no conflict of interest. The founding sources had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: The World Health Organization recognises the importance of natural environments for human health. Evidence for natural environment-health associations comes largely from single countries or regions, with varied approaches to measuring natural environment exposure. We present a standardised approach to measuring neighbourhood natural environment exposure in cities in different regions of Europe., Methods: The Positive Health Effects of the Natural Outdoor environment in TYPical populations of different regions in Europe (PHENOTYPE) study aimed to explore the mechanisms linking natural environment exposure and health in four European cities (Barcelona, Spain; Doetinchem, the Netherlands; Kaunas, Lithuania; and Stoke-on-Trent, UK). Common GIS protocols were used to develop a hierarchy of natural environment measures, from simple measures (e.g., NDVI, Urban Atlas) using Europe-wide data sources, to detailed measures derived from local data that were specific to mechanisms thought to underpin natural environment-health associations (physical activity, social interaction, stress reduction/restoration). Indicators were created around residential addresses for a range of straight line and network buffers (100 m-1 km)., Results: For simple indicators derived from Europe-wide data, we observed differences between cities, which varied with different indicators (e.g., Kaunas and Doetinchem had equal highest mean NDVI within 100 m buffer, but mean distance to nearest natural environment in Kaunas was more twice that in Doetinchem). Mean distance to nearest natural environment for all cities suggested that most participants lived close to some kind of natural environments (64 ± 58-363 ± 281 m; mean 180 ± 204 m). The detailed classification highlighted marked between-city differences in terms of prominent types of natural environment. Indicators specific to mechanisms derived from this classification also captured more variation than the simple indicators. Distance to nearest and count indicators showed clear differences between cities, and those specific to the mechanisms showed within-city differences for Barcelona and Doetinchem., Conclusions: This paper demonstrates the feasibility and challenges of creating comparable GIS-derived natural environment exposure indicators across diverse European cities. Mechanism-specific indicators showed within- and between-city variability that supports their utility for ecological studies, which could inform more specific policy recommendations than the traditional proxies for natural environment access.

Background: Evidence is growing for the beneficial impacts of natural outdoor environments on health. However, most of the evidence has focused on green spaces and little evidence is available on health benefits of blue spaces and about possible mediators and modifiers of such impacts. We investigated the association between natural outdoor environments (separately for green and blue spaces) and health (general and mental) and its possible mediators and modifiers., Methods: Cross-sectional data from adults interviewed in Catalonia (Spain) between 2010 and 2012 as part of the Catalonia Health Survey were used. The collected data included sociodemographic characteristics, self-perceived general health, mental health, physical activity and social support. Indicators of surrounding greenness and access to natural outdoor environments within 300 m of the residence and degree of urbanization were derived for residential addresses. Associations were estimated using logistic regression and negative binominal models., Results: Green spaces were associated with better self-perceived general health and better mental health, independent of degree of urbanization. The associations were more consistent for surrounding greenness than for access to green spaces. The results were consistent for different buffers, and when stratifying for socioeconomic status. Slightly stronger associations were found for women and residents of non-densely populated areas. No association was found between green spaces and social contacts and physical activity. The results for blue spaces were not conclusive., Conclusion: Green spaces are associated with better general and mental health across strata of urbanization, socioeconomic status, and genders. Mechanisms other than physical activity or social support may explain these associations., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce., Objectives: We aimed to simultaneously evaluate health benefits and risks associated with different types of greenness in children, in terms of sedentary behavior (represented by excessive screen time), obesity, current asthma, and allergic rhinoconjunctivitis., Methods: We conducted a cross-sectional study of a population-based sample of 3,178 schoolchildren (9-12 years old) in Sabadell, Spain, in 2006. Information on outcomes and covariates was obtained by questionnaire. We measured residential surrounding greenness as the average of satellite-derived Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, 500 m, and 1,000 m around each home address. Residential proximity to green spaces was defined as living within 300 m of a forest or a park, as separate variables. We used logistic regression models to estimate associations separately for each exposure-outcome pair, adjusted for relevant covariates., Results: An interquartile range increase in residential surrounding greenness was associated with 11-19% lower relative prevalence of overweight/obesity and excessive screen time, but was not associated with current asthma and allergic rhinoconjunctivitis. Similarly, residential proximity to forests was associated with 39% and 25% lower relative prevalence of excessive screen time and overweight/obesity, respectively, but was not associated with current asthma. In contrast, living close to parks was associated with a 60% higher relative prevalence of current asthma, but had only weak negative associations with obesity/overweight or excessive screen time., Conclusion: We observed two separable patterns of estimated health benefits and risks associated with different types of greenness.

Evidence of the impact of green spaces on pregnancy outcomes is limited with no report on how this impact might vary by ethnicity. We investigated the association between residential surrounding greenness and proximity to green spaces and birth weight and explored the modification of this association by ethnicity and indicators of individual (maternal education) and neighbourhood (Index of Multiple Deprivation) socioeconomic status. Our study was based on 10,780 singleton live-births from the Born in Bradford cohort, UK (2007-2010). We defined residential surrounding greenness as average of satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 50 m, 100 m, 250 m, 500 m and 1000 m around each maternal home address. Residential proximity to green spaces was defined as living within 300 m of a green space with an area of ≥ 5000 m(2). We utilized mixed effects models to estimate adjusted change in birth weight associated with residential surrounding greenness as well as proximity to green spaces. We found a positive association between birth weight and residential surrounding greenness. Furthermore, we observed an interaction between ethnicity and residential surrounding greenness in that for White British participants there was a positive association between birth weight and residential surrounding greenness whereas for participants of Pakistani origin there was no such an association. For surrounding greenness in larger buffers (500 m and 1000 m) there were some indications of stronger associations for participants with lower education and those living in more deprived neighbourhoods which were not replicated for surrounding greenness in smaller buffer sizes (i.e. 50 m, 100 m, and 250 m). The findings for residential proximity to a green space were not conclusive. Our study showed that residential surrounding greenness is associated with better foetal growth and this association could vary between different ethnic and socioeconomic groups., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome., Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project., Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures., Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Land Use Regression (LUR) models have been used to describe and model spatial variability of annual mean concentrations of traffic related pollutants such as nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (PM). No models have yet been published of elemental composition. As part of the ESCAPE project, we measured the elemental composition in both the PM10 and PM2.5 fraction sizes at 20 sites in each of 20 study areas across Europe. LUR models for eight a priori selected elements (copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)) were developed. Good models were developed for Cu, Fe, and Zn in both fractions (PM10 and PM2.5) explaining on average between 67 and 79% of the concentration variance (R(2)) with a large variability between areas. Traffic variables were the dominant predictors, reflecting nontailpipe emissions. Models for V and S in the PM10 and PM2.5 fractions and Si, Ni, and K in the PM10 fraction performed moderately with R(2) ranging from 50 to 61%. Si, NI, and K models for PM2.5 performed poorest with R(2) under 50%. The LUR models are used to estimate exposures to elemental composition in the health studies involved in ESCAPE.

Land use regression models (LUR) frequently use leave-one-out-cross-validation (LOOCV) to assess model fit, but recent studies suggested that this may overestimate predictive ability in independent data sets. Our aim was to evaluate LUR models for nitrogen dioxide (NO2) and particulate matter (PM) components exploiting the high correlation between concentrations of PM metrics and NO2. LUR models have been developed for NO2, PM2.5 absorbance, and copper (Cu) in PM10 based on 20 sites in each of the 20 study areas of the ESCAPE project. Models were evaluated with LOOCV and "hold-out evaluation (HEV)" using the correlation of predicted NO2 or PM concentrations with measured NO2 concentrations at the 20 additional NO2 sites in each area. For NO2, PM2.5 absorbance and PM10 Cu, the median LOOCV R(2)s were 0.83, 0.81, and 0.76 whereas the median HEV R(2) were 0.52, 0.44, and 0.40. There was a positive association between the LOOCV R(2) and HEV R(2) for PM2.5 absorbance and PM10 Cu. Our results confirm that the predictive ability of LUR models based on relatively small training sets is overestimated by the LOOCV R(2)s. Nevertheless, in most areas LUR models still explained a substantial fraction of the variation of concentrations measured at independent sites.

Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.