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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 metabolites. Organic food consumption was negatively associated with OP metabolites.Discussion:Fish consumption is related to higher PFAS, Hg, and As exposures. In addition, fruit consumption is a source of exposure to OPs. https://doi-org.proxy.insermbiblio.inist.fr/10.1289/EHP5324

Background Public engagement in the research of environmental epidemiological problems is becoming an important measure to empower citizens to identify the local environmental and health problems and to explain different environmental exposures affect estimates for males and females. This HORIZON2020 CitieS-Health Kaunas Pilot study examines the relationship between urban built and social environment, health behaviors, and health in men and women. Methods This cross-sectional study included 1086 18–74-year-old participants residing in 11 districts of Kaunas city, Lithuania. Using GIS, we measured traffic flow, noise, NO2, PM2.5, PM10, and greenness NDVI for the participants’ home addresses, determined participants’ perceptions of environmental quality, linked this information with personal sociodemographic data, and used multivariate logistic regression to assess the associations with health issues (physician-diagnosed chronic disease and self-rated general health) in men and women. Results Men and women similar rated the quality of the neighborhood environment, except for air pollution and satisfaction with the public transport in the district. The traffic-related health associations were stronger for women than for men. The prevalence of poor health increased with the increasing age of men and women, yet no significant differences between gender health risks were found in the total sample. Perceived air pollution, irregular visits to green space, and chronic diseases were consistently associated with poor health risks in men and women, yet part-time jobs and low income had a higher impact on women’s poor health. Conclusions Quality of the built neighborhood, air pollution, irregular visits to the green space, and chronic disease had a joint effect on the magnitude of the prevalence of poor health in men and women. Our results suggest that decreasing air pollution and improving the urban built neighborhood supporting citizens’ physical activity in green spaces, might reduce health risks for all.

Background The aims of this study were to explore associations of the distance and use of urban green spaces with the prevalence of cardiovascular diseases (CVD) and its risk factors, and to evaluate the impact of the accessibility and use of green spaces on the incidence of CVD among the population of Kaunas city (Lithuania). Methods We present the results from a Kaunas cohort study on the access to and use of green spaces, the association with cardiovascular risk factors and other health-related variables, and the risk of cardiovascular mortality and morbidity. A random sample of 5,112 individuals aged 45-72 years was screened in 2006-2008. During the mean 4.41 years follow-up, there were 83 deaths from CVD and 364 non-fatal cases of CVD among persons free from CHD and stroke at the baseline survey. Multivariate Cox proportional hazards regression models were used for data analysis. Results We found that the distance from people’s residence to green spaces was not related to the prevalence of health-related variables. However, the prevalence of cardiovascular risk factors and the prevalence of diabetes mellitus were significantly lower among park users than among non-users. During the follow up, an increased risk of non-fatal and fatal CVD combined was observed for those who lived ≥629.61 m from green spaces (3rd tertile of distance to green space) (hazard ratio (HR) = 1.36), and the risk for non-fatal CVD–for those who lived ≥347.81 m (2nd and 3rd tertile) and were not park users (HR = 1.66) as compared to men and women who lived 347.8 m or less (1st tertile) from green space. Men living further away from parks (3rd tertile) had a higher risk of non-fatal and fatal CVD combined, compared to those living nearby (1st tertile) (HR = 1.51). Compared to park users living nearby (1st tertile), a statistically significantly increased risk of non-fatal CVD was observed for women who were not park users and living farther away from parks (2nd and 3rd tertile) (HR = 2.78). Conclusion Our analysis suggests public health policies aimed at promoting healthy lifestyles in urban settings could produce cardiovascular benefits.

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project ( http://www.projecthelix.eu ). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1 H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates Absolute IDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated ( r  > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.

Although age is generally measured by the number of years since birth, many factors contribute to the rate at which a person physically ages. In adults, linking these measurements to age gives a measure of overall health and resilience. This ‘biological age’ offers a better prediction of remaining life and disease risk than the number of years lived. Multiple factors can be used to calculate biological age, such as measuring the length of telomeres – protective caps on the end of chromosomes – which shorten as people age. The rate at which they shorten can give an indication of how quickly someone is ageing. Researchers can also study epigenetic factors: these mechanisms lead to certain genes being switched on or off, and they can be combined into a ‘epigenetic clock’ to assess biological age. However, compared with adults, the relationship between biological age and child health and developmental maturity is less well understood. Robinson et al. studied 1,173 school-aged children from six European countries, measuring telomere length, epigenetic factors and other biological indicators related to metabolism and the immune system. The relationships between these factors and an array of child developmental measures such as height, weight, behaviour and the age of onset of puberty were established. The findings showed that biological age indicators are only weakly linked to each other in children. Despite this, biological age was related to greater amount of body fat across all tested indicators – which is also associated with biological age in adults and is an important determinant of lifespan. Among several observed effects on development, analysis found that shorter telomere length and older epigenetic age were associated with greater behavioural problems, suggesting they may be detrimental to child development. On the other hand, a greater age due to metabolic and immune related changes was associated with greater cognitive and behavioural maturity. Environmental factors were also linked to biological ageing, with children exposed to smoking in their homes or while their mother was pregnant displaying an older epigenetic age. Robinson et al. showed that biological ageing in children is multifaceted and can have both beneficial and harmful impacts on development. This knowledge is important for identifying early life risk factors that might influence healthy ageing in later life. Future work will help researchers to understand these complex interactions and the long-term consequences for health and well-being.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences. Obesity encompasses numerous interconnected pathological mechanisms. Here, the authors show that integrating multi-omics data uncovers distinct molecular profiles and prenatal factors linked to childhood obesity and metabolic dysfunction, providing insights for early prevention and intervention strategies.

ObjectivesThe aim of this study was to investigate the associations between surrounding greenness levels and asthma among children, and to explore a possible change of this association by the distance of the residence to a city park.DesignA nested case–control study.SettingChildren aged 4−6 years residing at their current address since birth in Kaunas, Lithuania, whose mothers were recruited in 2007–2009 to the KANC newborns cohort study.ParticipantsThe participants were 1489 children whose parents in 2012–2013 filled in the questionnaires and agreed to participate in the study.Primary and secondary outcome measuresWe estimated clinically diagnosed asthma risk factors. The surrounding greenness was measured as the average of the satellite-based Normalised Difference Vegetation Index (NDVI) within the buffers of 100, 300 and 500 m from each child's home address, and the distance to a city park was defined as the distance to the nearest city park. Multivariate logistic regression was performed to study the relationship between the greenness exposures and asthma adjusted for relevant covariates.ResultsAn increase in the NDVI (>median) in buffers of 100, 300 and 500 m was associated with a slightly increased risk of asthma, while an IQR increase in NDVI-100 m statistically significantly increased the risk of asthma (OR 1.43, 95% CI 1.10 to 1.85). The stratified analysis by surrounding greenness revealed indications of stronger associations for children with higher surrounding greenness (NDVI-100>median) and those living farther away from parks (>1000 m), compared to NDVI-100≤median and the distance to a city park >1000 m (OR 1.47, 95% CI 0.56 to 3.87).ConclusionsA higher level of the surrounding greenness was associated with a slightly increased relative risk of asthma in children. Further investigation is needed to elucidate the influence of city parks and neighbourhood greenness levels on asthma.

Background: The complex impact of environmental and social factors on preschool children being overweight/obese is unclear. We examined the associations between the levels of green space exposure and the risk of being overweight/obese for 4–6 year-old children and assessed the impact of maternal education on these associations. Methods: This cross-sectional study included 1489 mother-child pairs living in Kaunas, Lithuania, in 2012–2013. We assessed children overweight/obesity by standardized questionnaires using international body mass index cut-off points, and the level of greenness exposures by satellite-derived normalized difference vegetation index (NDVI) of each child’s home and by the distance to a nearest city park. The maternal education was used as the SES indicator. We used logistic regression models to investigate the strength of the associations. Results: Children from families with poorer maternal education, pathological mother-child relations and smoking mothers, and living in areas with less greenness exposure (NDVI-100 m), had significantly higher odds ratios of being overweight/obese. Lower maternal education and distance to a city park modified the effect of greenness cover level exposure on the risk of children being overweight/obese. Conclusions: Higher greenness exposure in the residential settings has beneficial effects on children’s physical development. The green spaces exposures for psychosocial stress management is recommended as a measure to prevent overweight/obesity among children.

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1 H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N -methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children’s diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Cells can fine-tune which genes they activate, when and at which levels using a range of chemical marks on the DNA and certain proteins that help to organise the genome. One well-known example of such ‘epigenetic tags’ is DNA methylation, whereby a methyl group is added onto particular positions in the genome. Many factors – including environmental effects such as diet – control DNA methylation, allowing an organism to adapt to ever-changing conditions. An expression quantitative trait methylation (eQTM) is a specific position of the genome whose DNA methylation status regulates the activity of a given gene. A catalogue of eQTMs would be useful in helping to reveal how the environment and disease impacts the way cells work. Yet, currently, the relationships between most epigenetic tags and gene activity remains unclear, especially in children. To fill this gap, Ruiz-Arenas et al. studied DNA methylation in blood samples from over 800 healthy children across Europe. Amongst all tested DNA methylation sites, 22,000 (5.7% of total) were associated with the expression of a gene – and therefore were eQTMs; reciprocally, 9,000 genes (15.3% of all tested genes) were linked to at least one methylation site, leading to a total of 40,000 pairs of DNA methylation sites and genes. Most often, eQTMs regulated the expression of nearby genes – but only half controlled the gene that was the closest to them. Age and the genetic background of the individuals influenced the nature of eQTMs. This catalogue is a useful resource for the scientific community to start understanding the relationship between epigenetics and gene activity. Similar studies are now needed for other tissues and age ranges. Overall, extending our knowledge of eQTMs may help reveal how life events lead to illness, and could inform prevention efforts.