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BACKGROUND: Results from observational and experimental studies indicate that exposure to air pollutants during gestation reduces birth weight, whereas little is known on potential cardiometabolic consequences for the offspring at adulthood.OBJECTIVES: Our aim was to evaluate the long-term effects of gestational exposure to diesel engine exhaust (DE) on adult offspring phenotype in a rabbit model.METHODS: The protocol was designed to mimic human exposure in large European cities. Females rabbits were exposed to diluted (1 mg/m3) DE (exposed, n = 9) or clean air (controls, n = 7), from 3 days after mating, 2 h/d and 5 d/wk in a nose-only inhalation system throughout gestation (gestation days 3-27). After birth and weaning, 72 offspring (47 exposed and 25 controls) were raised until adulthood (7.5 months) to evaluate their cardio-metabolic status, including the monitoring of body weight and food intake, fasting biochemistry, body composition (iDXA), cardiovascular parameters and glucose tolerance. After a metabolic challenge (high fat diet in males and gestation in females), animals were euthanized for postmortem phenotyping.RESULTS: Sex-specific responses to maternal exposure were observed in adult offspring. Age-related increases in blood pressure (p = 0.058), glycaemia (p = 0.029), and perirenal fat mass (p = 0.026) as well as reductions in HDL-cholesterol (p = 0.025) and fat-to-body weight ratio (p = 0.011) were observed in exposed males, suggesting a metabolic syndrome. Almost only trends were observed in exposed females with higher triglycerides and decreased bone density compared to control females. Metabolic challenges triggered or amplified some biological responses, especially in females.CONCLUSIONS: In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath’s Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early age

Background: Multiple omics technologies are increasingly applied to detect early, subtle molecular responses to environmental stressors for future disease risk prevention. However, there is an urgent need for further evaluation of stability and variability of omics profiles in healthy individuals, especially during childhood. Methods: We aimed to estimate intra-, inter-individual and cohort variability of multi-omics profiles (blood DNA methylation, gene expression, miRNA, proteins and serum and urine metabolites) measured 6 months apart in 156 healthy children from five European countries. We further performed a multi-omics network analysis to establish clusters of co-varying omics features and assessed the contribution of key variables (including biological traits and sample collection parameters) to omics variability. Results: All omics displayed a large range of intra- and inter-individual variability depending on each omics feature, although all presented a highest median intra-individual variability. DNA methylation was the most stable profile (median 37.6% inter-individual variability) while gene expression was the least stable (6.6%). Among the least stable features, we identified 1% cross-omics co-variation between CpGs and metabolites (e.g. glucose and CpGs related to obesity and type 2 diabetes). Explanatory variables, including age and body mass index (BMI), explained up to 9% of serum metabolite variability. Conclusions: Methylation and targeted serum metabolomics are the most reliable omics to implement in single time-point measurements in large cross-sectional studies. In the case of metabolomics, sample collection and individual traits (e.g. BMI) are important parameters to control for improved comparability, at the study design or analysis stage. This study will be valuable for the design and interpretation of epidemiological studies that aim to link omics signatures to disease, environmental exposures, or both

Perchlorate, nonylphénol, rayons ultraviolets, ozone, DDT, changement climatique… L’ensemble des facteurs environnementaux qui influencent la santé humaine compose une vaste jungle dans laquelle il n’est pas aisé de s’orienter. Cet ouvrage en dresse un état complet, scientifique, rigoureux et dépassionné. Il présente les mécanismes toxicologiques et les effets sanitaires des contaminants, qu’ils existent de longue date, comme le plomb, les particules et les polluants organiques persistants, ou qu’ils soient plus récents, comme certains pesticides, les bisphénols et autres perturbateurs endocriniens.Les substances nocives et les effets sanitaires liés aux catastrophes environnementales visibles, telles que celles de Seveso, Tchernobyl, Yusho ou Minamata, mais aussi aux catastrophes silencieuses, liées aux contaminants invisibles de notre environnement, sont exposés. Les grands noms qui ont fait progresser les connaissances en santé environnementale sont également passés en revue à l’occasion d’un fascinant voyage sur toute la planète et à travers l’Histoire.Ce livre permettra à chacun de comprendre les enjeux complexes de la transition épidémiologique qui, dans les pays industrialisés, a consacré le règne des maladies chroniques (cancers, pathologies cardiovasculaires…), ainsi que la nature multifactorielle de ces problèmes de santé, et la délicate notion de causalité en médecine. Il donne aussi un aperçu des principales options en débat concernant la gestion du risque — prévenir ou guérir, informer ou interdire, agir au nom du principe de précaution... En présentant divers exemples de la façon dont les risques posés par les contaminants environnementaux sont aujourd’hui gérés, il met en lumière la grande hétérogénéité des réactions de notre société face aux menaces sanitaires.Accessible, clair, informé et précis, ce livre s’adresse autant à des étudiants en médecine, biologie et sciences de l’environnement qu’à un public soucieux de connaître les arguments scientifi

Perchlorate, nonylphénol, rayons ultraviolets, ozone, DDT, changement climatique… L’ensemble des facteurs environnementaux qui influencent la santé humaine compose une vaste jungle dans laquelle il n’est pas aisé de s’orienter. Cet ouvrage en dresse un état complet, scientifique, rigoureux et dépassionné. Il présente les mécanismes toxicologiques et les effets sanitaires des contaminants, qu’ils existent de longue date, comme le plomb, les particules et les polluants organiques persistants, ou qu’ils soient plus récents, comme certains pesticides, les bisphénols et autres perturbateurs endocriniens.Les substances nocives et les effets sanitaires liés aux catastrophes environnementales visibles, telles que celles de Seveso, Tchernobyl, Yusho ou Minamata, mais aussi aux catastrophes silencieuses, liées aux contaminants invisibles de notre environnement, sont exposés. Les grands noms qui ont fait progresser les connaissances en santé environnementale sont également passés en revue à l’occasion d’un fascinant voyage sur toute la planète et à travers l’Histoire.Ce livre permettra à chacun de comprendre les enjeux complexes de la transition épidémiologique qui, dans les pays industrialisés, a consacré le règne des maladies chroniques (cancers, pathologies cardiovasculaires…), ainsi que la nature multifactorielle de ces problèmes de santé, et la délicate notion de causalité en médecine. Il donne aussi un aperçu des principales options en débat concernant la gestion du risque — prévenir ou guérir, informer ou interdire, agir au nom du principe de précaution... En présentant divers exemples de la façon dont les risques posés par les contaminants environnementaux sont aujourd’hui gérés, il met en lumière la grande hétérogénéité des réactions de notre société face aux menaces sanitaires.Accessible, clair, informé et précis, ce livre s’adresse autant à des étudiants en médecine, biologie et sciences de l’environnement qu’à un public soucieux de connaître les arguments scientifi

Perchlorate, nonylphénol, rayons ultraviolets, ozone, DDT, changement climatique… L’ensemble des facteurs environnementaux qui influencent la santé humaine compose une vaste jungle dans laquelle il n’est pas aisé de s’orienter. Cet ouvrage en dresse un état complet, scientifique, rigoureux et dépassionné. Il présente les mécanismes toxicologiques et les effets sanitaires des contaminants, qu’ils existent de longue date, comme le plomb, les particules et les polluants organiques persistants, ou qu’ils soient plus récents, comme certains pesticides, les bisphénols et autres perturbateurs endocriniens.Les substances nocives et les effets sanitaires liés aux catastrophes environnementales visibles, telles que celles de Seveso, Tchernobyl, Yusho ou Minamata, mais aussi aux catastrophes silencieuses, liées aux contaminants invisibles de notre environnement, sont exposés. Les grands noms qui ont fait progresser les connaissances en santé environnementale sont également passés en revue à l’occasion d’un fascinant voyage sur toute la planète et à travers l’Histoire.Ce livre permettra à chacun de comprendre les enjeux complexes de la transition épidémiologique qui, dans les pays industrialisés, a consacré le règne des maladies chroniques (cancers, pathologies cardiovasculaires…), ainsi que la nature multifactorielle de ces problèmes de santé, et la délicate notion de causalité en médecine. Il donne aussi un aperçu des principales options en débat concernant la gestion du risque — prévenir ou guérir, informer ou interdire, agir au nom du principe de précaution... En présentant divers exemples de la façon dont les risques posés par les contaminants environnementaux sont aujourd’hui gérés, il met en lumière la grande hétérogénéité des réactions de notre société face aux menaces sanitaires.Accessible, clair, informé et précis, ce livre s’adresse autant à des étudiants en médecine, biologie et sciences de l’environnement qu’à un public soucieux de connaître les arguments scientifi

In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathwa

Atmospheric pollution has major health effects on directly exposed subjects but intergenerational consequences are poorly characterized. We previously reported that diesel engine exhaust (DE) could lead to structural changes in the placenta of in utero exposed rabbits (first generation, F1). The effects of maternal exposure to DE were further studied on second-generation (F2) rabbits. Pregnant F0 females were exposed to filtered, diluted DE (1 mg/m3, median particle diameter: 69 nm) or clean filtered air (controls) for 2 h/day, 5 days/week by nose-only exposure during days 3-27 post-conception (dpc). Adult female offspring (F1) were mated to control males: F1 tissues and F2 foeto-placental units were collected at 28 dpc and placental structure and gene expression (microarray) analysed. Fatty acid profiles were determined in foetal and maternal plasma, maternal liver and placenta. In F1, compared to controls, hepatic neutral lipid contents were increased in exposed animals without change in the blood biochemistry. In F2, the placental lipid contents were higher, with higher monounsaturated fatty acids and reduced pro-inflammatory arachidonic acid (AA), without placental structural changes. Conversely, the proportion of anti-inflammatory n-3 polyunsaturated fatty acids in F2 plasma was increased while that of AA was decreased. Gene set enrichment analyses (GSEA) of F2 placenta transcriptomic data identified that the proteasome complex and ubiquitin pathways genes were over-represented and ion channel function and inflammation pathways genes were under-represented in exposed animals. These preliminary results demonstrate that diesel engine exhaust exposure and in utero indirect exposure should be considered as a programming factor within the context of the DOHaD (Developmental Origins of Health and Disease) with a probable intergenerational transmission.

Background:Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status.Objectives:Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother–child pairs from six European birth cohorts (n=818 mothers and 1,288 children).Methods:We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE).Results:Maternal high (≥4 times/week) versus low (<2 times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio=1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GM ratio=1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GM ratio=1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GM ratio=4.87; 95% CI: 2.57, 9.23) levels. In children, high (≥3 times/week) versus low (<1.5 times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GM ratio=1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GM ratio=1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GM ratio=1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GM ratio=3.87 (95% CI: 1.91, 4.31) and GM ratio=2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP

Background:Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status.Objectives:Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother–child pairs from six European birth cohorts (n=818 mothers and 1,288 children).Methods:We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE).Results:Maternal high (≥4 times/week) versus low (<2 times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio=1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GM ratio=1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GM ratio=1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GM ratio=4.87; 95% CI: 2.57, 9.23) levels. In children, high (≥3 times/week) versus low (<1.5 times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GM ratio=1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GM ratio=1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GM ratio=1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GM ratio=3.87 (95% CI: 1.91, 4.31) and GM ratio=2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP

Background:Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status.Objectives:Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother–child pairs from six European birth cohorts (n=818 mothers and 1,288 children).Methods:We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE).Results:Maternal high (≥4 times/week) versus low (<2 times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio=1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GM ratio=1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GM ratio=1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GM ratio=4.87; 95% CI: 2.57, 9.23) levels. In children, high (≥3 times/week) versus low (<1.5 times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GM ratio=1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GM ratio=1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GM ratio=1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GM ratio=3.87 (95% CI: 1.91, 4.31) and GM ratio=2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP

Background:Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status.Objectives:Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother–child pairs from six European birth cohorts (n=818 mothers and 1,288 children).Methods:We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE).Results:Maternal high (≥4 times/week) versus low (<2 times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio=1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GM ratio=1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GM ratio=1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GM ratio=4.87; 95% CI: 2.57, 9.23) levels. In children, high (≥3 times/week) versus low (<1.5 times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GM ratio=1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GM ratio=1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GM ratio=1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GM ratio=3.87 (95% CI: 1.91, 4.31) and GM ratio=2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP

BACKGROUND: Several epidemiologic designs allow studying fecundability, the monthly probability of pregnancy occurrence in non-contracepting couples in the general population. These designs may, to varying extents, suffer from attenuation bias and other biases. We aimed to compare the main designs: incident and prevalent cohorts, pregnancy-based, and current duration approaches.METHODS: A realistic simulation model produced individual reproductive lives of a fictitious population. We drew random population samples according to each study design, from which the cumulative probability of pregnancy was estimated. We compared the abilities of the designs to highlight the impact of an environmental factor influencing fecundability, relying on the Cox model with censoring after 12 or 6 months.RESULTS: Regarding the estimation of the cumulative probability of pregnancy, the pregnancy-based approach was the most prone to bias. When we considered a hypothetical factor associated with a hazard ratio (HR) of pregnancy of 0.7, the estimated HR was in the 0.78-0.85 range, according to designs. This attenuation bias was largest for the prevalent cohort and smallest for the current duration approach, which had the largest variance. The bias could be limited in all designs by censoring durations at 6 months.CONCLUSION: Attenuation bias in HRs cannot be ignored in fecundability studies. Focusing on the effect of exposures during the first 6 months of unprotected intercourse through censoring removes part of this bias. For risk factors that can accurately be assessed retrospectively, retrospective fecundity designs, although biased, are not much more strongly so than logistically more intensive designs entailing follow-up.

BACKGROUND: Several epidemiologic designs allow studying fecundability, the monthly probability of pregnancy occurrence in non-contracepting couples in the general population. These designs may, to varying extents, suffer from attenuation bias and other biases. We aimed to compare the main designs: incident and prevalent cohorts, pregnancy-based, and current duration approaches.METHODS: A realistic simulation model produced individual reproductive lives of a fictitious population. We drew random population samples according to each study design, from which the cumulative probability of pregnancy was estimated. We compared the abilities of the designs to highlight the impact of an environmental factor influencing fecundability, relying on the Cox model with censoring after 12 or 6 months.RESULTS: Regarding the estimation of the cumulative probability of pregnancy, the pregnancy-based approach was the most prone to bias. When we considered a hypothetical factor associated with a hazard ratio (HR) of pregnancy of 0.7, the estimated HR was in the 0.78-0.85 range, according to designs. This attenuation bias was largest for the prevalent cohort and smallest for the current duration approach, which had the largest variance. The bias could be limited in all designs by censoring durations at 6 months.CONCLUSION: Attenuation bias in HRs cannot be ignored in fecundability studies. Focusing on the effect of exposures during the first 6 months of unprotected intercourse through censoring removes part of this bias. For risk factors that can accurately be assessed retrospectively, retrospective fecundity designs, although biased, are not much more strongly so than logistically more intensive designs entailing follow-up.

BACKGROUND: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs.METHODS: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cutoffs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputations and applied inverse probability-weighting methods to correct for loss to follow-up.RESULTS: We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio [OR] for ADHD symptoms of 0.95, 95% confidence interval [CI] = 0.89, 1.01 per 10 µg/m increase in NO2 and 0.98, 95% CI = 0.80, 1.19 per 5 µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range.CONCLUSIONS: There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3-10 years. See video abstract at, http://links.lww.com/EDE/B379.

Multicentre studies are common in epidemiological research aiming at identifying disease risk factors. A major advantage of multicentre over single-centre studies is that, by including a larger number of participants, they allow consideration of rare outcomes and exposures. Their multicentric nature introduces some complexities at the step of data analysis, in particular when it comes to controlling for confounding by centre, which is the focus of this tutorial. Commonly, epidemiologists use one of the following options: pooling all centre-specific data and adjusting for centre using fixed effects; adjusting for centre using random effects; or fitting centre-specific models and combining the results in a meta-analysis. Here, we illustrate the similarities of and differences between these three modelling approaches, explain the reasons why they may provide different conclusions and offer advice on which model to choose depending on the characteristics of the study. Two key issues to examine during the analyses are to distinguish within-centre from between-centre associations, and the possible heterogeneity of the effects (of exposure and/or confounders) by centre. A real epidemiological study is used to illustrate a situation in which these various options yield different results. A synthetic dataset and R and Stata codes are provided to reproduce the results.

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatur

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatur

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatur

BACKGROUND AND OBJECTIVES: Ambient air pollution is controllable, and it is one of the greatest environmental threats to human health. Studies conducted worldwide have provided evidence that maternal exposure to ambient air pollution during pregnancy enhances the risk of low birth weight at term (TLBW, <2500g among infants born ≥37 completed weeks of gestation), a maker of intrauterine growth restriction (IUGR), and suggest that some subgroups of pregnant women who are smoking, of low or high body-mass index (BMI), low socioeconomic status (SES) or asthma are more vulnerable towards the effect of ambient air pollution. The aim of this commentary is to review the published literature on the association between ambient air pollution and TLBW regarding increased vulnerability for the above-mentioned subgroups.RESULTS: Although more than fifty epidemiological studies have examined the associations between ambient air pollution and TLBW to date, we only identified six studies that examined the potential effect modification of the association between ambient air pollution and TLBW by the above listed maternal risk factors. Two studies assessed effect modification caused by smoking on the association between ambient air pollution and TLBW. The adjusted odds ratio (OR) for TLBW associated with exposure to ambient air pollution were in one study higher among women who smoked during pregnancy, as compared to the OR of non-smoking women, while in the other study the association was in the opposite direction. The association of ambient air pollution and TLBW were higher among women characterized by extreme BMI (two studies) and low SES compared to non-obese women or women of higher SES (four studies), respectively. Only one study reported the estimated effects among asthmatic and non-asthmatic women and no statistically significant effect modification was evident for the risk of TLBW associated with ambient air pollution.CONCLUSION AND RECOMMENDATIONS: The c

BACKGROUND: There is growing interest in examining the simultaneous effects of multiple exposures and, more generally, the effects of mixtures of exposures, as part of the exposome concept (being defined as the totality of human environmental exposures from conception onwards). Uncovering such combined effects is challenging owing to the large number of exposures, several of them being highly correlated. We performed a simulation study in an exposome context to compare the performance of several statistical methods that have been proposed to detect statistical interactions.METHODS: Simulations were based on an exposome including 237 exposures with a realistic correlation structure. We considered several statistical regression-based methods, including two-step Environment-Wide Association Study (EWAS2), the Deletion/Substitution/Addition (DSA) algorithm, the Least Absolute Shrinkage and Selection Operator (LASSO), Group-Lasso INTERaction-NET (GLINTERNET), a three-step method based on regression trees and finally Boosted Regression Trees (BRT). We assessed the performance of each method in terms of model size, predictive ability, sensitivity and false discovery rate.RESULTS: GLINTERNET and DSA had better overall performance than the other methods, with GLINTERNET having better properties in terms of selecting the true predictors (sensitivity) and of predictive ability, while DSA had a lower number of false positives. In terms of ability to capture interaction terms, GLINTERNET and DSA had again the best performances, with the same trade-off between sensitivity and false discovery proportion. When GLINTERNET and DSA failed to select an exposure truly associated with the outcome, they tended to select a highly correlated one. When interactions were not present in the data, using variable selection methods that allowed for interactions had only slight costs in performance compared to methods that only searched for main effects.CONCLUSIONS: GLINTER

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. pressure measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.

Les perturbateurs endocriniens, vous en entendez de plus en plus parler…Mais les messages qui parviennent jusqu’à vos oreilles sont souvent complexes, imprécis ou alarmistes. Dès lors, comment vous y retrouver ? Comment vous faire une idée juste et raisonnable des répercussions que pourraient avoir ces mystérieux polluants dans votre vie quotidienne ? Les perturbateurs endocriniens sont omniprésents dans votre environnement ; comment les repérer dans votre assiette, votre salle de bains, votre maison ou votre lieu de travail ?Quelle est leur part de responsabilité dans les troubles de la fertilité, les cancers, l’obésité ou les troubles du comportement comme l’autisme ou l’hyperactivité ? Quelles sont les personnes les plus vulnérables ? Où en est la recherche dans ce domaine ?Un médecin journaliste et un chercheur en environnement et santé vous livrent toutes les clés pour démêler cet écheveau et vous proposent de précieux conseils pratiques et simples à mettre en œuvre pour réduire votre exposition.Quelques bonnes habitudes à prendre qui pourraient bien vous aider à protéger votre santé et l’environnement ! Consulter la préface de Michel Cymes

Les perturbateurs endocriniens, vous en entendez de plus en plus parler…Mais les messages qui parviennent jusqu’à vos oreilles sont souvent complexes, imprécis ou alarmistes. Dès lors, comment vous y retrouver ? Comment vous faire une idée juste et raisonnable des répercussions que pourraient avoir ces mystérieux polluants dans votre vie quotidienne ? Les perturbateurs endocriniens sont omniprésents dans votre environnement ; comment les repérer dans votre assiette, votre salle de bains, votre maison ou votre lieu de travail ?Quelle est leur part de responsabilité dans les troubles de la fertilité, les cancers, l’obésité ou les troubles du comportement comme l’autisme ou l’hyperactivité ? Quelles sont les personnes les plus vulnérables ? Où en est la recherche dans ce domaine ?Un médecin journaliste et un chercheur en environnement et santé vous livrent toutes les clés pour démêler cet écheveau et vous proposent de précieux conseils pratiques et simples à mettre en œuvre pour réduire votre exposition.Quelques bonnes habitudes à prendre qui pourraient bien vous aider à protéger votre santé et l’environnement ! Consulter la préface de Michel Cymes

Les perturbateurs endocriniens, vous en entendez de plus en plus parler…Mais les messages qui parviennent jusqu’à vos oreilles sont souvent complexes, imprécis ou alarmistes. Dès lors, comment vous y retrouver ? Comment vous faire une idée juste et raisonnable des répercussions que pourraient avoir ces mystérieux polluants dans votre vie quotidienne ? Les perturbateurs endocriniens sont omniprésents dans votre environnement ; comment les repérer dans votre assiette, votre salle de bains, votre maison ou votre lieu de travail ?Quelle est leur part de responsabilité dans les troubles de la fertilité, les cancers, l’obésité ou les troubles du comportement comme l’autisme ou l’hyperactivité ? Quelles sont les personnes les plus vulnérables ? Où en est la recherche dans ce domaine ?Un médecin journaliste et un chercheur en environnement et santé vous livrent toutes les clés pour démêler cet écheveau et vous proposent de précieux conseils pratiques et simples à mettre en œuvre pour réduire votre exposition.Quelques bonnes habitudes à prendre qui pourraient bien vous aider à protéger votre santé et l’environnement ! Consulter la préface de Michel Cymes