Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome. Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ. 2014. The Human Early-Life Exposome (HELIX): project rationale and design. Environ Health Perspect 122:535–544; http://dx.doi.org/10.1289/ehp.1307204

Background: Green spaces have been associated with improved mental health in children; however, available epidemiological evidence on their impact on child behavioral development is scarce. Objectives: We investigated the impact of contact with green spaces and blue spaces (beaches) on indicators of behavioral development and symptoms of attention deficit/hyperactivity disorder (ADHD) in schoolchildren. Methods: This study was based on a sample of 2,111 schoolchildren (7–10 years of age) from 36 schools in Barcelona in 2012. We obtained data on time spent in green spaces and beaches and Strengths and Difficulties Questionnaires (SDQ) from parents, and ADHD/DSM-IV questionnaires from teachers. Surrounding greenness was abstracted as the average Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, and 500 m around each home address. Proximity to green spaces was defined as living within 300 m of a major green space (≥ 0.05 km2). We applied quasi-Poisson mixed-effects models (with school random effect) to separately estimate associations between indicators of contact with green spaces and SDQ and ADHD total and subscale scores. Results: We generally estimated beneficial associations between behavioral indicators and longer time spent in green spaces and beaches, and with residential surrounding greenness. Specifically, we found statistically significant inverse associations between green space playing time and SDQ total difficulties, emotional symptoms, and peer relationship problems; between residential surrounding greenness and SDQ total difficulties and hyperactivity/inattention and ADHD/DSM-IV total and inattention scores; and between annual beach attendance and SDQ total difficulties, peer relationship problems, and prosocial behavior. For proximity to major green spaces, the results were not conclusive. Conclusion: Our findings support beneficial impacts of contact with green and blue spaces on behavioral development in schoolchildren. Citation: Amoly E, Dadvand P, Forns J, López-Vicente M, Basagaña X, Julvez J, Alvarez-Pedrerol M, Nieuwenhuijsen MJ, Sunyer J. 2014. Green and blue spaces and behavioral development in Barcelona schoolchildren: the BREATHE Project. Environ Health Perspect 122:1351–1358; http://dx.doi.org/10.1289/ehp.1408215

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 31 472 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 signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.

Background: Air pollution from traffic has been associated with cardiorespiratory diseases in children and adults, but there is little information on its potential neurotoxic effects. This study aimed to investigate the association between exposure to nitrogen dioxide (NO ₂ ), as a marker of traffic-related air pollution, and cognitive development in children. Methods: A population-based birth cohort from southern Spain was followed from the age of 4 years for 1 year. Complete data for analyses were gathered on 210 children living in urban and rural areas. NO ₂ exposure was predicted by means of land use regression models. A standardised version of the McCarthy Scales of Children's Abilities (MSCA) was used to assess children's motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between exposure to NO ₂ and MSCA outcomes, adjusting for potential confounders. Results: A negative effect of NO ₂ was found across all MSCA subscales, despite low predicted NO ₂ exposure levels (5–36 μg/m ³ ). Children exposed to higher NO ₂ (>24.75 μg/m ³ ) showed a decrease of 4.19 points in the general cognitive score and decreases of 6.71, 7.37 and 8.61 points in quantitative, working memory and gross motor areas, respectively. However, except for gross motor function, associations were not statistically significant. Conclusion: Although results were not statistically significant, the associations found between exposure to NO ₂ and cognitive functions suggest that traffic-related air pollution may have an adverse effect on neurodevelopment, especially early in life, even at low exposure levels.

Background Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children, but a few cohort studies measuring smoking data prospectively have studied its specific effects on the cognitive abilities of pre-schoolers. Method A birth cohort was set up in Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A total of 420 (87% of those eligible) children had complete data for final analyses at age 4 years. Interviewer-administered questionnaires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child. A standardized version of the McCarthy Scales of Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive capabilities. Multivariable regressions were used with MCSA's assessed outcomes adjusting for: home location, maternal alcohol consumption, mother's social class and level of education during pregnancy, parity, marital status, father's education level, child's gender, birth weight and height, breastfeeding duration, passive smoking, school season, age during test administration and evaluator (psychologist). Results A high global consistency in maternal smoking habits was found (total agreement = 88.7%). Maternal social class and education level were inversely associated with maternal smoking behaviour. Maternal smoking during pregnancy (in cig./day) was associated with a decrease (in points) of children's global cognitive score [β = −0.60, (95% CI: −1.10; −0.09)]; as well as global cognitive sub-areas like verbal score [β = −0.59, (95% CI: −1.11; −0.07)]; quantitative score [β = −0.57, (95% CI: −1.08; −0.06)]; executive function score [β = −0.71, (95% CI: −1.23; −0.20)]; and working memory score [β = –0.46, (95% CI: −0.92; −0.01)]. Conclusion Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years.

p,p′-DDT (bis[p-chlorophenyl]-1,1,1-trichloroethane) is a persistent organochlorine compound that has been used worldwide as an insecticide. The authors evaluated the association of cord serum levels of DDT and its metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), with neurodevelopment at age 4 years. Two birth cohorts in Ribera d'Ebre and Menorca (Spain) were recruited between 1997 and 1999 (n = 475). Infants were assessed at age 4 years by using the McCarthy Scales of Children's Abilities. Organochlorine compounds were measured in cord serum. Children's diet and parental sociodemographic information was obtained through questionnaire. Results showed that DDT cord serum concentration at birth was inversely associated with verbal, memory, quantitative, and perceptual-performance skills at age 4 years. Children whose DDT concentrations in cord serum were >0.20 ng/ml had mean decreases of 7.86 (standard error, 3.21) points in the verbal scale and 10.86 (standard error, 4.33) points in the memory scale when compared with children whose concentrations were <0.05 ng/ml. These associations were stronger among girls. Prenatal exposure to background, low-level concentrations of DDT was associated with a decrease in preschoolers' cognitive skills. These results should be considered when evaluating the risk and benefits of spraying DDT during antimalaria and other disease-vector campaigns.