Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess ...whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development.
We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon EC, nitrogen dioxide NO2, and ultrafine particle number UFP; 10-700 nm) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% 95% CI 5.6%-8.8% versus 11.5% 95% CI 8.9%-12.5% improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%-23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation.
Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.
Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions.
We evaluated the variability of ...urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children.
154 pregnant women and 152 children from six European countries were enrolled in 2014–2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80.
All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40–0.59) to good (0.60–0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15–20 urines each would be necessary to obtain an ICC above 0.80.
This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months.
•Urinary measurement variability can bias dose-response functions.•We evaluated the variability of 24 metabolites in pregnant women and children.•An alternative sampling strategy based on pooled urine is proposed.•The pooling strategy does not solve variability for most of these metabolites.
Characterization of the “exposome”, the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on ...chronic diseases.
Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6–11 years in 6 European birth cohorts.
Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures.
In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities.
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•The early-life exposome is high dimensional and not easily reducible to fewer components.•Correlations between exposures within the same exposure group can be high.•Correlations between exposures in different exposure groups are low.•The exposome varies strongly by location and by life period.
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.
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 (
mothers and 1,288 children).
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).
Maternal high (
) versus low (
) fish consumption was associated with 15% higher PCBs geometric mean (GM)
; 95% confidence interval (CI): 1.02, 1.29, 42% higher perfluoroundecanoate (PFUnDA) (
; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (
; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (
; 95% CI: 2.57, 9.23) levels. In children, high (
) versus low (
) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (
; 95% CI: 1.08, 1.40), 36% higher PFUnDA (
; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (
; 95% CI: 1.22, 1.54), and
higher Hg and As
(95% CI: 1.91, 4.31) and
(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.
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/10.1289/EHP5324.
The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for ...disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
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.
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•A wide range of pre- and postnatal environmental exposures affects child behavior.•The exposome includes outdoor, indoor, chemical, lifestyle and social exposures.•Maternal tobacco ...smoke and car traffic increased behavioural problems in children.•Child sleep, healthy diet and higher family social capital reduced symptoms.•Child exposure to lead, copper, indoor air pollution, increased symptoms.
Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior.
We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6–11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner’s Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent’s reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 1.09; 1.59) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides.
Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk.
En aquest article es descriu el problema de la contaminació atmosfèrica centrant-se en els efectes que produeix en la salut humana. Així, descriu breument què és la contaminació, per què ens pot ...afectar, i quina evidència hi ha dels problemes de salut que pot causar. L'article resumeix efectes establerts, com els respiratoris i cardiovasculars, i d'altres que són àrees actives de recerca, com els possibles efectes cognitius. En aquest darrer cas, es resumeixen els resultats d'un estudi que es va dur a terme recentment a Barcelona i es descriuen els objectius d'un nou projecte que està en fase de preparació.
•PFAS mixture exposure was associated with higher HDL cholesterol and lower waist circumference.•Postnatal PFAS were the main contributors to the identified mixtures.•Prenatal PFOA was positively ...related with the pro-inflammatory biomarker IL-1beta.
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.
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