Maternal Seafood Consumption during Pregnancy and Cardiovascular Health of Children at 11 Years of Age.

Nutrition is critical during pregnancy for the healthy growth of the developing infant, who is fully dependent on maternal dietary omega-3 supply for development. Fatty fish, a main dietary source of omega-3, is associated with decreased cardiovascular risk in adults. We conducted a longitudinal study based on a mother-offspring cohort as part of the project Infancia y Medio Ambiente (INMA) in order to assess whether fish intake during pregnancy relates to cardiovascular health in children. A total of 657 women were included and followed throughout pregnancy until birth, and their children were enrolled at birth and followed up until age 11-12. A semi-quantitative food frequency questionnaire was used to assess the daily intake of foods during the 1st and 3rd trimesters of pregnancy. Cardiovascular assessments included arterial stiffness (assessed by carotid-femoral pulse wave velocity [PWV]) and retinal microcirculation (photographic assessment of central retinal arteriolar and venular equivalent [CRAE and CRVE]). The association between maternal fish consumption and cardiovascular outcomes of offspring at 11 years of age was evaluated using multivariable linear regression models. There were no statistically significant differences in any cardiovascular endpoint in children whose mothers had a higher fish consumption during pregnancy compared to those with a lower fish consumption. We found a slightly higher PWV (ß = 0.1, 95% CI = 0.0; 0.2, p for trend = 0.047) in children whose mothers had a higher consumption of canned tuna during the 1st trimester of pregnancy. Fish intake during pregnancy was found to be unrelated to the offspring's cardiovascular health at 11 years of age. The beneficial cardiovascular effects of fish consumption during pregnancy on the offspring are still inconclusive.

Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts.

BACKGROUND: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). OBJECTIVES: We investigated associations between urban environment exposures during pregnancy and PPD. METHODS: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686-30,716 depending on exposure; representing 26-46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3-18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. RESULTS: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. DISCUSSION: The study findings suggest that exposure to PM10, road traffic noise and blue spaces in pregnancy may increase PPD risk, however future studies should explore this causally.

Urban environment during pregnancy and childhood and white matter microstructure in preadolescence in two European birth cohorts.

Growing evidence suggests that urban environment may influence cognition and behavior in children, but the underlying pollutant and neurobiological mechanisms are unclear. We evaluated the association of built environment and urban natural space indicators during pregnancy and childhood with brain white matter microstructure in preadolescents, and examined the potential mediating role of air pollution and road-traffic noise. We used data of the Generation R Study, a population-based birth cohort in Rotterdam, the Netherlands (n = 2725; 2002-2006) for the primary analyses. Replication of the main findings was attempted on an independent neuroimaging dataset from the PELAGIE birth cohort, France (n = 95; 2002-2006). We assessed exposures to 12 built environment and 4 urban natural spaces indicators from conception up to 9 years of age. We computed 2 white matter microstructure outcomes (i.e., average of fractional anisotropy (FA) and mean diffusivity (MD) from 12 white matte tracts) from diffusion tensor imaging data. Greater distance to the nearest major green space during pregnancy was associated with higher whole-brain FA (0.001 (95%CI 0.000; 0.002) per 7 m increase), and higher land use diversity during childhood was associated with lower whole-brain MD (-0.001 (95%CI -0.002; -0.000) per 0.12-point increase), with no evidence of mediation by air pollution nor road-traffic noise. Higher percentage of transport and lower surrounding greenness during pregnancy were associated with lower whole-brain FA, and road-traffic noise mediated 19% and 52% of these associations, respectively. We found estimates in the same direction in the PELAGIE cohort, although confidence intervals were larger and included the null. This study suggests an association between urban environment and white matter microstructure, mainly through road-traffic noise, indicating that greater access to green space nearby might promote white matter development.

Urban environment during pregnancy and lung function, wheezing, and asthma in school-age children. The generation R study.

The urban environment during pregnancy may influence child's respiratory health, but scarce evidence exists on systematic evaluation of multiple urban exposures (e.g., air pollution, natural spaces, noise, built environment) on children's lung function, wheezing, and asthma development. We aimed to examine the association of the urban environment during pregnancy with lung function, preschool wheezing, and school-age asthma. We included 5624 mother-child pairs participating in a population-based prospective birth cohort. We estimated 30 urban environmental exposures including air pollution, road traffic noise, traffic, green spaces, blue spaces, and built environment during pregnancy. At 10 years of age, lung function was measured by spirometry. Information on preschool wheezing and physician-diagnosed school-age asthma was obtained from multiple questionnaires. We described single-exposure associations with respiratory outcomes using an exposome-wide association study. We also identified patterns of urban exposures with hierarchical clustering on principal components analysis and examined their associations with respiratory outcomes using multivariate regression models. Single-exposure analyses showed associations of higher particulate matter (PM) with lower mid-expiratory flow (FEF25-75%) (e.g., for PM < 2.5 µm of diameter [PM2.5] z-score = -0.06 [-0.09, -0.03]) and higher forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) (e.g., for PM2.5 FEV1 0.05 [0.02, 0.08]) after correction for multiple-hypothesis testing. Cluster analysis described three patterns of urban exposures during pregnancy and showed that the cluster characterised by higher levels of air pollution, noise, walkability, street connectivity, and lower levels of natural spaces were associated with lower FEF25-75% (-0.08 [-0.17, 0.00]), and higher odds of preschool wheezing (1.21 [1.03, 1.43]). This study shows that the characteristics of the urban environment during pregnancy are of relevance to the offspring's respiratory health during childhood.

Social inequalities, green and blue spaces and mental health in 6-12 years old children participating in the INMA cohort.

Availability of green and blue spaces in the area of residence has been related to various health outcomes during childhood, including mental health. These environmental exposures are not evenly distributed among socioeconomic groups, which may increase social inequalities in mental health. The mechanisms through which natural environments may promote mental health are numerous and diverse. This study aimed to explore 1) the potential associations of socioeconomic variables (SES and maternal education attainment) with mental health scores and residential greenness, blueness and NO2 metrics, and, 2) the association between greenness and blueness metrics and mental health scores of children in the Spanish INfancia y Medio Ambiente (INMA) birth cohort at two different time points. The study samples were composed of 1738 six-to eight-year-olds (49% female) and 1449 ten-to twelve-year-olds (living in Asturias, Gipuzkoa, Sabadell and Valencia, Spain. Individual Normalized Difference Vegetation Index (NDVI) values in 100-, 300- and 500-m buffers and availability of green and blue spaces >5000 m2 in 300-m buffers were calculated using Geographic Information Systems software. Residential NO2 values were estimated using land use regression models. Internalizing, externalizing and total problems scores were obtained with the Strengths and Difficulties Questionnaire (SDQ). Linear and logistic mixed-effects models revealed unequal distribution of environmental exposures by SES and maternal education but did not show statistically significant associations between greenness and blueness metrics and mental health indicators. The protective effect of green and blue spaces on children's mental health could not be confirmed in this study and therefore further research is required.

Modelling socioeconomic position as a driver of the exposome in the first 18 months of life of the NINFEA birth cohort children.

BACKGROUND: The exposome drivers are less studied than its consequences but may be crucial in identifying population subgroups with unfavourable exposures. OBJECTIVES: We used three approaches to study the socioeconomic position (SEP) as a driver of the early-life exposome in Turin children of the NINFEA cohort (Italy). METHODS: Forty-two environmental exposures, collected at 18 months of age (N = 1989), were classified in 5 groups (lifestyle, diet, meteoclimatic, traffic-related, built environment). We performed cluster analysis to identify subjects sharing similar exposures, and intra-exposome-group Principal Component Analysis (PCA) to reduce the dimensionality. SEP at childbirth was measured through the Equivalised Household Income Indicator. SEP-exposome association was evaluated using: 1) an Exposome Wide Association Study (ExWAS), a one-exposure (SEP) one-outcome (exposome) approach; 2) multinomial regression of cluster membership on SEP; 3) regressions of each intra-exposome-group PC on SEP. RESULTS: In the ExWAS, medium/low SEP children were more exposed to greenness, pet ownership, passive smoking, TV screen and sugar; less exposed to NO2, NOX, PM25abs, humidity, built environment, traffic load, unhealthy food facilities, fruit, vegetables, eggs, grain products, and childcare than high SEP children. Medium/low SEP children were more likely to belong to a cluster with poor diet, less air pollution, and to live in the suburbs than high SEP children. Medium/low SEP children were more exposed to lifestyle PC1 (unhealthy lifestyle) and diet PC2 (unhealthy diet), and less exposed to PC1s of the built environment (urbanization factors), diet (mixed diet), and traffic (air pollution) than high SEP children. CONCLUSIONS: The three approaches provided consistent and complementary results, suggesting that children with lower SEP are less exposed to urbanization factors and more exposed to unhealthy lifestyles and diet. The simplest method, the ExWAS, conveys most of the information and is more replicable in other populations. Clustering and PCA may facilitate results interpretation and communication.

Associations of green and blue space exposure in pregnancy with epigenetic gestational age acceleration.

Early life is seen as a particularly sensitive period for environmental exposures. Natural space exposure during pregnancy has been associated with offspring health. Epigenetic gestational age acceleration, a discrepancy between clinical and DNA methylation-based gestational age, may underlie these associations. In 1359 mother-newborn pairs from the population-based Generation R Study, we examined the associations of natural space exposure, defined as surrounding greenness, distance to major green and blue (water) space, and size of the blue space during pregnancy with offspring epigenetic gestational age acceleration. Natural space exposure was based on participants' geocoded addresses, and epigenetic gestational age acceleration was calculated from cord blood DNA methylation using Bohlin's and Knight's epigenetic clocks. Sensitivity analyses were conducted in a subgroup of newborns with optimal pregnancy dating, based on last menstrual period. Surrounding greenness, measured in normalized difference vegetation index values, was intermediate (median 0.4, IQR 0.2), and 84% and 56% of the participants had a major green or blue space near their home address, respectively. We did not observe associations of natural space availability during pregnancy with offspring epigenetic gestational age acceleration. This could imply that epigenetic gestational age acceleration in cord blood does not underlie the effects of residential natural space availability in pregnancy on offspring health. Future studies could investigate whether residential natural space availability during pregnancy is associated with offspring differential DNA methylation at other CpGs than those included in the epigenetic gestational clocks.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children.

Importance: Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. Objective: To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. Design, Setting, and Participants: This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. Exposures: Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. Main Outcomes and Measures: Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. Results: The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (ß, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (ß, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. Conclusions and Relevance: With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.

Urban environment and health behaviours in children from six European countries.

BACKGROUND: Urban environmental design is increasingly considered influential for health and wellbeing, but evidence is mostly based on adults and single exposure studies. We evaluated the association between a wide range of urban environment characteristics and health behaviours in childhood. METHODS: We estimated exposure to 32 urban environment characteristics (related to the built environment, traffic, and natural spaces) for home and school addresses of 1,581 children aged 6-11 years from six European cohorts. We collected information on health behaviours including total amount of overall moderate-to-vigorous physical activity, physical activity outside school hours, active transport, sedentary behaviours and sleep duration, and developed patterns of behaviours with principal component analysis. We used an exposure-wide association study to screen all exposure-outcome associations, and the deletion-substitution-addition algorithm to build a final multi-exposure model. RESULTS: In multi-exposure models, green spaces (Normalized Difference Vegetation Index, NDVI) were positively associated with active transport, and inversely associated with sedentary time (22.71 min/day less (95 %CI -39.90, -5.51) per interquartile range increase in NDVI). Residence in densely built areas was associated with more physical activity and less sedentary time, and densely populated areas with less physical activity outside school hours and more sedentary time. Presence of a major road was associated with lower sleep duration (-4.80 min/day (95 %CI -9.11, -0.48); compared with no major road). Results for the behavioural patterns were similar. CONCLUSIONS: This multicohort study suggests that areas with more vegetation, more building density, less population density and without major roads are associated with improved health behaviours in childhood.

Lutein and Zeaxanthin Intake during Pregnancy and Visual Function in Offspring at 11-12 Years of Age.

(1) Background: Lutein and zeaxanthin (L&Z) are essential dietary nutrients that are a crucial component of the human macula, contributing to visual functioning. They easily cross the placental barrier, so that retinal deposition commences during foetal development. This study aims to assess associations between maternal L&Z intake during pregnancy and offspring visual function at 11-12 years. (2) Methods: Using the Spanish INfancia y Medio Ambiente project (INMA) Sabadell birth cohort, 431 mother-child pairs were analysed. L&Z data were obtained from food frequency questionnaires (FFQ) at week 12 and 32 of pregnancy, alongside other nutritional and sociodemographic covariates. Contrast vision (CS) and visual acuity (VA) were assessed using the automated Freiburg Acuity and Contrast Testing (FRACT) battery. Low CS and VA were defined as being below the 20th cohort centile. Associations were explored using multiple logistic regression. (3) Results: After controlling for potential confounders, L&Z intake during the 1st and 3rd trimester did not reveal any statistically significant association with either CS or VA in offspring at age 11/12 years. (4) Conclusions: No evidence of a long-term association between L&Z intake during pregnancy and visual function in offspring was found. Further larger long-term studies including blood L&Z levels are required to confirm this result.

Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health.

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 1H 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.

Prenatal exposure to phthalates and phenols and preclinical vascular health during early adolescence.

BACKGROUND AND AIM: Exposure to endocrine-disrupting chemicals may increase cardiovascular risk from early life, but studies in children have shown inconsistent results, most focused on analysis of single chemicals, and none included measures of micro-vascularization as early preclinical markers. This study aimed to evaluate the association between prenatal exposure to phthalates and phenols and macro- and microvascular health during early adolescence. METHODS: Using data from a Spanish birth cohort (n = 416), prenatal exposure to eight phthalate metabolites and seven phenols (bisphenol A, four parabens, benzophenone-3, triclosan) were assessed using first and/or third trimester spot-urine concentrations. Macrovascular health (systolic and diastolic blood pressure (SBP and DBP, mmHg), pulse wave velocity (PWV, m/s)) and microvascular health (central retinal artery/vein equivalent (CRAE/CRVE, µm)), were measured at 11 years old. Linear regression models assessed associations for individual chemicals and Bayesian weighted quantile sum regression (BWQS) evaluated the overall association of the phthalate and phenol mixture with cardiovascular health. RESULTS: In single exposure models, bisphenol-A was associated with decreased PWV (ß per doubling of exposure = -0.06; 95% CI: -0.10, -0.01). Mono-iso-butyl phthalate was associated with an increase in CRAE (ß = 1.89; 95% CI: 0.34, 3.44). Methyl- and butyl-parabens were associated with a decrease in CRVE (ß = -0.71; 95% CI: -1.41, -0.01) and (ß = -0.96; 95% CI: -1.57, -0.35), respectively. No statistically significant associations were observed between any of the exposures and SBP or DBP. BWQS models showed no evidence of associations between the phthalate and phenol mixture and any of the outcomes. CONCLUSIONS: Our results provide little evidence to suggest that prenatal exposure to phthalates and phenols is associated with macro- or microvascular health during early adolescence, except a few associations with certain compounds. Errors in exposure measurement and reduced variability in cardiovascular measures at this early age limit our ability to draw strong conclusions.

Early-childhood BMI trajectories in relation to preclinical cardiovascular measurements in adolescence.

Cardiovascular diseases are the leading causes of morbidity and mortality. Overweight, obesity, and accelerated growth during early childhood have been associated with adverse cardiovascular outcomes in later life. Few studies have assessed whether trajectories of accelerated growth in early childhood are associated with preclinical cardiovascular measurements. We aimed to evaluate the associations between childhood body mass index (BMI) growth trajectories and measures of macro- and microvascular function in early adolescence. Measurements of macrovascular function (systolic and diastolic blood pressure (SBP and DBP), pulse wave velocity (PWV), and microvascular function (central retinal arteriolar/veinular equivalent) were assessed at 11 years old in a Spanish birth cohort study (n = 489). BMI trajectories from birth to 9 years were identified using latent class growth analysis. Multiple linear regression assessed the associations between the BMI trajectories and macro- and microvascular function. Compared to children with average birth size and slower BMI gain (reference), children with a lower birth size and accelerated BMI gain had increased SBP [ß = 6.57; (95% CI 4.00, 9.15)], DBP [ß = 3.65; (95% CI 1.45, 5.86)], and PWV [ß = 0.14; (95% CI 0.01, 0.27)]. Children with higher birth size and accelerated BMI gain had increased SBP [ß = 4.75; (95% CI 1.79, 7.71) compared to the reference. No significant associations between BMI trajectories and the microvascular measurements were observed. In conclusion, we found that childhood BMI trajectories characterized by accelerated growth are associated with preclinical macrovascular measurements in young adolescents.

Advancing tools for human early lifecourse exposome research and translation (ATHLETE): Project overview.

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE's results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward.

Infection induced SARS-CoV-2 seroprevalence and heterogeneity of antibody responses in a general population cohort study in Catalonia Spain.

Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We applied a well-validated multiplex serology test in 5000 participants of a general population study in Catalonia in blood samples collected from end June to mid November 2020. Based on responses to fifteen isotype-antigen combinations, we detected a seroprevalence of 18.1% in adults (n = 4740), and modeled extrapolation to the general population of Catalonia indicated a 15.3% seroprevalence. Antibodies persisted up to 9 months after infection. Immune profiling of infected individuals revealed that with increasing severity of infection (asymptomatic, 1-3 symptoms, ≥ 4 symptoms, admitted to hospital/ICU), seroresponses were more robust and rich with a shift towards IgG over IgA and anti-spike over anti-nucleocapsid responses. Among seropositive participants, lower antibody levels were observed for those ≥ 60 years vs < 60 years old and smokers vs non-smokers. Overweight/obese participants vs normal weight had higher antibody levels. Adolescents (13-15 years old) (n = 260) showed a seroprevalence of 11.5%, were less likely to be tested seropositive compared to their parents and had dominant anti-spike rather than anti-nucleocapsid IgG responses. Our study provides an unbiased estimate of SARS-CoV-2 seroprevalence in Catalonia and new evidence on the durability and heterogeneity of post-infection immunity.

Prenatal and postnatal exposure to PFAS and cardiometabolic factors and inflammation status in children from six European cohorts.

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.

Urban environment and obesity and weight-related behaviours in primary school children.

BACKGROUND: Urban environments are characterised by many factors that may influence children's lifestyle and increase the risk of childhood obesity, but multiple urban exposures have scarcely been studied. OBJECTIVE: We evaluated the association between multiple urban exposures and childhood obesity outcomes and weight-related behaviours. METHODS: We conducted a cross-sectional study including 2213 children aged 9-12 years in Sabadell, Spain. We estimated ambient air pollution, green spaces, built and food environment, road traffic and road traffic noise at residential addresses through a total of 28 exposure variables in various buffers. Childhood obesity outcomes included body mass index (BMI), waist circumference and body fat. Weight-related behaviours included diet (fast food and sugar-sweetened beverage consumption), physical activity, sedentary behaviour, sleep duration and well-being. Associations between exposures (urban environment) and outcomes (obesity and behaviours) were estimated in single and multiple-exposure regression models and in a hierarchical clustering on principal components (HCPC) analysis. RESULTS: Forty percent of children were overweight or obese. In single exposure models, very few associations were observed between the urban exposures and obesity outcomes or weight-related behaviours after correction for multiple testing. In multiple exposure models, PMcoarse, denser unhealthy food environment and land use mix were statistically significant associated with childhood obesity outcomes (e.g 17.7 facilities/km2 increase of unhealthy food environment (OR overweight/obesity status) = 1.20 [95% CI: 1.01; 1.44]). Cluster analysis identified 5 clusters of urban exposures. Compared to the most neutral cluster, the cluster with high air pollution, road traffic, and road noise levels was associated with a higher BMI and higher odds of overweight and obesity (ß (zBMI) = 0.17, [95% CI: 0.01, 0.17]; OR (overweight/obesity) = 1.36, [95% CI: 0.99, 1.85]); the clusters were not associated with the weight-related behaviours. CONCLUSIONS: This systematic study of many exposures in the urban environment suggests that an exposure pattern characterised by higher levels of ambient air pollution, road traffic and road traffic noise is associated with increased childhood obesity risk and that PMcoarse, land use mix and food environment are separately associated with obesity risk. These findings require follow-up in longitudinal studies and different settings.

Prenatal and childhood exposure to air pollution and traffic and the risk of liver injury in European children.

Nonalcoholic fatty liver disease is the most prevalent pediatric chronic liver disease. Experimental studies suggest effects of air pollution and traffic exposure on liver injury. We present the first large-scale human study to evaluate associations of prenatal and childhood air pollution and traffic exposure with liver injury. METHODS: Study population included 1,102 children from the Human Early Life Exposome project. Established liver injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and cytokeratin-18, were measured in serum between ages 6-10 years. Air pollutant exposures included nitrogen dioxide, particulate matter <10 µm (PM10), and <2.5 µm. Traffic measures included traffic density on nearest road, traffic load in 100-m buffer, and inverse distance to nearest road. Exposure assignments were made to residential address during pregnancy (prenatal) and residential and school addresses in year preceding follow-up (childhood). Childhood indoor air pollutant exposures were also examined. Generalized additive models were fitted adjusting for confounders. Interactions by sex and overweight/obese status were examined. RESULTS: Prenatal and childhood exposures to air pollution and traffic were not associated with child liver injury biomarkers. There was a significant interaction between prenatal ambient PM10 and overweight/obese status for alanine aminotransferase, with stronger associations among children who were overweight/obese. There was no evidence of interaction with sex. CONCLUSION: This study found no evidence for associations between prenatal or childhood air pollution or traffic exposure with liver injury biomarkers in children. Findings suggest PM10 associations maybe higher in children who are overweight/obese, consistent with the multiple-hits hypothesis for nonalcoholic fatty liver disease pathogenesis.

In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. APPROACH AND RESULTS: We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 µg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1ß, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSIONS: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.