Search

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Background: Peer connections in school classrooms play an important role in social–emotional development and mental health. However, research on the association between children's peer relationships and white matter connections in the brain is scarce. We studied associations between peer relationships in the classroom and white matter structural connectivity in a pediatric population-based sample. Methods: Bullying and victimization, as well as rejection and acceptance, were assessed in classrooms in 634 children at age 7. White matter microstructure (fractional anisotropy (FA), mean diffusivity (MD)) was measured with diffusion tensor imaging at age 10. We examined global metrics of white matter microstructure and used Tract-Based Spatial Statistics (TBSS) for voxel-wise associations. Results: Peer victimization was associated with higher global FA and lower global MD and peer rejection was associated with lower global MD; however, these associations did not remain after multiple testing correction. Voxel-wise TBSS results for peer victimization and rejection were in line with global metrics both in terms of direction and spatial extent of the associations, with associated voxels (pFWE

Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6–11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (−1.25; −2.10, −0.40), house crowding (−0.39; −0.62, −0.16), and child environmental tobacco smoke (ETS) (−0.89; −1.42, −0.35), were all associated with lower CPM scores. Indoor PM2.5 exposure was associated with lower N-Back scores (−0.09; −0.16, −0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely and cross-sectionally associate with cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality., Graphical abstract Prenatal and childhood exposome-wide associations with child fluid intelligence (CPM). The exposures selected by Deletion-substitution-addition algorithm are represented by a triangle. Child fluid intelligence is mainly associated with childhood exposome, fast-food (negative association, left sided) and organic food consumption (positive, right sided), house crowding (negative, left sided), and child environmental tobacco smoke (ETS, negative, left sided). Image 1, Highlights • Previous evidence for environmental risk factor associations with neurodevelopment is based on analyses of single exposures. • We systematically analysed multiple environmental exposures in relation to child neurodevelopment. • The findings describe a list of outcome-related exposures: Diet, house crowding, indoor air pollution and tobacco smoke. • The findings show methodological complexities of analysing multiple exposures and their associations with neurodevelopment.

Background There is a need to test the fetal programming theoretical framework in nutritional epidemiology. We evaluated whether maternal seafood intake during pregnancy was associated with 8-year-old attention outcomes after adjusting for previous child seafood intake and cognitive function. We also explored effect modification by several single nucleotide polymorphisms (SNPs) related with polyunsaturated fatty acid (PUFA) metabolism. Methods Our final analyses included 1644 mother-child pairs from the prospective INMA (INfancia y Medio Ambiente) cohort study (Spain, recruitment between 2003 and 2008). We used food frequency questionnaires to assess prenatal and postnatal seafood consumption of the mother-child pairs. We evaluated attention function of the children through the computer-based Attention Network Test (ANT) and we used the number of omission errors and the hit reaction time standard error (HRT-SE). Parents reported child attention deficit hyperactivity disorder (ADHD) symptoms using the Revised Conners’ Parent Rating Scale Short Form (CPRS-R: S). We measured seven candidate SNPs in a subsample of 845 children. We estimated associations using regression models, adjusting for family characteristics, child seafood intake and cognitive functions at early ages, and to explore SNP effect modifications. Results Higher total seafood intake during early pregnancy was associated with a reduction of child ANT omission errors, 5th quintile (median = 854 g/week) vs 1st quintile (median = 195 g/week), incidence risk ratio (IRR) 0.76; 95% CI = 0.61, 0.94. Similar results were observed after adjusting the models for child seafood intake and previous cognitive status. Lean, large and small fatty fish showed similar results, and generally similar but less robust associations were observed with the other attention outcomes. Shellfish and canned tuna showed weaker associations. The association patterns were weaker in late pregnancy and null in child seafood consumption. Child rs1260326 (glucokinase regulator, GCKR) and child/maternal rs2281591 (fatty acid elongase 2, ELOVL2) polymorphisms showed nominal P-value for interactions Conclusions After adjusting for previous child cognitive functions and child seafood intake, high pregnancy consumption (total, lean, small and large fatty fish) was independently associated with improvements of some 8-year-old attention outcomes. Genetic effect modification analyses suggest PUFA intake from seafood as a potential biological mechanism of such association.

DAL’s contribution to this paper is supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no 669545) and a UK National Institute of Health Senior Investigator (NF-0616-10102). TC’s contribution is supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle). MLV has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707404. The opinions expressed in this document refect only the author’s view. The European Commission is not responsible for any use that may be made of the information it contains. The INfancia y Medio Ambiente (INMA)-Sabadell cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; CP18/00018; PI041436; PI081151; PI1100610 incl. FEDER funds). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S). SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). JJ holds Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (Co-funded by European Social Fund “Investing in your future”). MC holds a Miquel ServetI cotract (CP16/00128) awarded by the Instituto de Salud Carlos III (co-funded by European Social Fund "Investing in your future"). The INMA-Asturias cohort is funded by grants from Instituto de Salud Carlos III (FISS PI 04/2018, FISS PI09/02311, FISS PI13/02429, FISS PI18/00909 including FEDER funds) and University of Oviedo. This study was funded by Instituto de Salud Carlos III through the projects ‘CP14/00108 & PI16/00261’ (co-funded by European Regional Development Fund ‘A way to make Europe’) (…), Alemany, S., Avella-García, C., Liew, Z., García-Esteban, R., Inoue, K., Cadman, T., López-Vicente, M., González, L., Riaño Galán, I., Andiarena, A., Casas, M., Margetaki, K., Strandberg-Larsen, K., Lawlor, D.A., El Marroun, H., Tiemeier, H., Iñiguez, C., Tardón, A., Santa-Marina, L., Júlvez, J., Porta, D., Chatzi, L., Sunyer, J.

Background The recent evidence of the short-term impact of air pollution on youth cognitive functions is based primarily on observational studies. Objectives We conducted a randomized controlled trial to assess whether purifying the air of the classrooms produced short-term changes in attention processes of adolescents. Methods We recruited a total of 2,123 adolescents (13–16 years old) in 33 high schools in Barcelona metropolitan area (Spain). In each school, adolescents from each class were randomly split into two equal-sized groups and assigned to two different classrooms. A set of two air cleaner devices with the same appearance (one recirculating and filtrating the air and the other only recirculating the air) was used. Each one of the devices was placed at random at one of the two classrooms. Students were masked to intervention allocation and had to complete several computerized activities for 1.5 h, including an attention test (Flanker task) to be performed at baseline and at the end of the intervention. The response speed consistency, expressed as hit reaction time standard error (HRT-SE, in ms), was measured as the primary outcome. Analyses were conducted using conditional linear regressions with classroom as strata, adjusted for variables that may differ from one class to another such as temperature, humidity and carbon dioxide concentration. Results Average levels of PM2.5 and black carbon throughout the 1.5 h of experiment were 89% and 87%, respectively, lower in the classrooms with air cleaner than in the control classrooms. No differences were found in the median of HRT-SE between classrooms with cleaned air and normal air (percent change: 1.37%, 95% confidence interval: −2.81%, 5.56%). Sensitivity analyses with secondary attention outcomes resulted in similar findings. Conclusions Cleaning the air of a classroom to reduce exposure to air pollutants for 1.5 h did not have an impact on the attention function of adolescents. Still, in light of previous evidence suggesting an association between air pollution and attention, further experimental studies should explore other short-term timescales of exposure and age ranges., The research leading to these results has received funding from “la Caixa” Foundation (ID 100010434) under the program RecerCaixa (2017 ACUP 00274). We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Jordi Julvez holds the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund “Investing in your future”). This study has been funded by Instituto de Salud Carlos III through the project “PI16/00261” (Co-funded by European Regional Development Fund “A way to make Europe”). We thank all the professors and students for their time and precious collaboration in this study. We would like to thank the following schools: Col.legi Kostka, Col.legi Padre Damián, Col.legi Sagrada Família-Horta, Col.legi Santíssima Trinitat, Escola Joan Pelegrí, Escola L'Horitzó, Escola Virolai, IES Leonardo da Vinci, IES Montserrat Roig, Institut Barri Besòs, Institut Celestí Bellera, Institut de Cornellà, Institut de la Roca del Vallès, Institut Doctor Puigvert, Institut Hipàtia d'Alexandria, Institut Icària. Institut Isaac Albéniz, Institut Jaume Balmes, Institut Joan Brossa, Institut Juan Manuel Zafra, Institut La Ribera, Institut Les Corts, Institut Marta Estrada, Institut Matadepera, Institut Moisès Broggi, Institut Narcís Monturiol, Institut Pau Claris, Institut Puig Castellar, Institut Sabadell, Institut Secretari Coloma, Institut Valldemossa, Institut Verdaguer, Vedruna Gràcia. Also, our thanks go to our colleagues participating in the fieldwork: Guillermo Rodriguez Gomez, Marta Ensesa Pomarola, Marta Torrens Tomey, Cristina Garcia-Narcué Moreno and Núria Pey.

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection. Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment. Data sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018. Study eligibility criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions. Study appraisal and synthesis methods: Studies were evaluated using the Cochrane Collaboration′s risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed. Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout.There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found. Limitations, conclusions, and implications of key findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence. Systematic review registration number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902). Keywords: Ionizing radiation, Low dose, Neurodevelopment, Epidemiology, Child health

Vitamin D deficiency during critical periods of development could lead to persistent brain alterations. We aimed to assess the association between maternal vitamin D-3, the major circulatory form of vitamin D, at pregnancy and neurodevelopmental outcomes during childhood, namely: behavioural problems, Attention Deficit and Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) symptoms, and social competence. This study included 2,107 mother-child pairs of a Spanish population-based birth cohort. Maternal plasma vitamin D-3 was measured in pregnancy. The outcomes were measured through questionnaires at 5, 8, 14, and 18 years old. We ran multivariate regression models adjusted for potential confounding variables. We found that per each 10 ng/mL increment of maternal vitamin D-3, children obtained higher social competence scores (coefficient =0.77; 95% CI=0.19, 1.35) at 5 years old. However, we observed null associations between maternal vitamin D-3 and total behavioural problems and ADHD and ASD symptoms in children from 5 to 18 years old. Further studies carried out in countries where the population is exposed to lower vitamin D levels are needed., The authors are grateful to all the teachers, parents and children who have participated in the INMA project for their generous collaborative efforts. We thank all the investigators who have collected information and samples from the participants. Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2; PI061756; PS0901958; PI14/00677 incl. FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigacion en Enfermedades Neurodegenerativas de La Caixa, and EC Contract No. QLK4-CT-2000-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; CPII/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundacio La marato de TV3 (090430), EU Commission (261357). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and MSII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017. Asturias: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), FIS-PI042018, FIS-PI09/02311, FIS-PI13/02429, FIS-PI18/00909, CIBERESP, Obra Social Cajastur/Fundacion Liberbank and UNIVERSIDAD DE OVIEDO. Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090 and FIS-PI13/02187), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain).

Background: Although previous studies have reported negative associations between exposure to air pollution and cognition, studies of the effects of prenatal and postnatal exposures in early childhood have been limited. Objectives: We sought to assess the role exposure to fine particulate matter ([Formula: see text]) during different prenatal and postnatal windows may play in children's cognitive development at school age. Methods: Within the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) Project, we estimated residential [Formula: see text] exposures by land use regression for the prenatal period and first seven postnatal years of 2,221 children from Barcelona, Spain. The participants ([Formula: see text]) completed computerized tests assessing working memory, attentiveness, and conflict network during four visits in 2012–2013. We used linear mixed effects and distributed lag models to assess the period of exposure to [Formula: see text] in association with cognitive development. Results: Inverse associations were identified between [Formula: see text] exposure during the fifth and sixth postnatal years and working memory, with boys showing much higher vulnerability. Regarding attention functions, exposure to higher [Formula: see text] levels during the prenatal period and from the fourth postnatal year were associated with a reduction in conflict network performance, though we found no association with attentiveness. The overall estimated cumulative effect of a [Formula: see text] increase in [Formula: see text] resulted in a reduction in the working memory [Formula: see text] score of [Formula: see text] [95% confidence interval (CI): [Formula: see text], [Formula: see text]] points and an increase in the conflict attentional network of 11.31 (95% CI: 6.05, 16.57) milliseconds, indicating a poorer performance. Conclusions: Early life exposure to [Formula: see text] was associated with a reduction in fundamental cognitive abilities, including working memory and conflict attentional network. https://doi.org/10.1289/EHP3169. The research leading to these results has received funding from the European Research Council (ERC-Advanced Grant) under grant agreement number 268479—the BREATHE project. We are grateful to A. Dalmau-Bueno for his help in estimating exposure to air pollution. We thank all the families participating in the study and particularly to the schools. P.D. is funded by a Juan de la Cierva fellowship (JCI-2011-09937) awarded by the Spanish Ministry of Science and Innovation.

This study was funded by Grants from Spanish Institute of Health Carlos III-Ministry of Economy and Competitiveness (INMA Network G03/176, CB06/02/0041, and FIS-FEDER: PI03/1615, PI04/1436, PI08/1151, PI04/2018, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI09/02647, PS09/00090, PI09/02311, MS11/0178, PI13/1944, PI13/2032, PI13/02429, PI16/1288, and PI17/00663), Generalitat de CatalunyaCIRIT 1999SGR 00241, JCI-2011–09771–MICINN, Generalitat Valenciana (Conselleria de Sanitat-048/2010 and 060/2010 and FISABIO-UGP 15-230, 15-244, and 15-249), Alicia Koplowitz Foundation, Universidad de Oviedo, Fundación Cajastur-Liberbank, Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and the Fundación Roger Torné. This study has been funded by Instituto de Salud Carlos III through the projects “CP14/00108 & PI16/00261” (Co-funded by European Regional Development Fund “A way to make Europe”). Jordi Julvez, Mònica Guxens and MariaJose Lopez-Espinosa hold a Miguel Servet contract (MS14/00108, MS13/00054 and MSII16/00051, respectively) awarded by the Spanish Institute of Health Carlos III (Ministry of Economy and Competitiveness)., Gignac, F., Romaguera, D., Fernández-Barrés, S., Phillipat, C., Garcia Esteban, R., López-Vicente, M., Vioque, J., Fernández-Somoano, A., Tardón, A., Iñiguez, C., Lopez-Espinosa, M.-J., García de la Hera, M., Amiano, P., Ibarluzea, J., Guxens, M., Sunyer, J., Julvez, J.

The human brain develops over an extended period; its maturation continues through adolescence and young adulthood. Studying trajectories of brain development in representative samples of the general population is important in order to understand exposures and stressors in the child’s and adult’s physical and social environment that shape human brain development. Early environments may be particularly important in their impact on mental health, learning and behavior in human societies. In this context, it is important – for both theoretical and practical reasons – to measure trajectories of brain development in large population-based epidemiological studies.[...]

Objective: To analyze associations between time spent sleeping, watching TV, engaging in cognitively stimulating activities, and engaging in physical activity, all at 4 years, and (1) attention-deficit/hyperactivity disorder (ADHD) symptoms and (2) behavior problems, both assessed at 7 years, in ADHD-free children at baseline. Method: In total, 817 participants of the Infancia y Medio Ambiente birth cohort, without ADHD at baseline, were included. At the 4-year follow-up, parents reported the time that their children spent sleeping, watching TV, engaging in cognitively stimulating activities, and engaging in physical activity. At the 7-year follow-up, parents completed the Conners' Parent Rating Scales and the Strengths and Difficulties Questionnaire, which measure ADHD symptoms and behavior problems, respectively. Negative binomial regression models were used to assess associations between the activities at 4 years and ADHD symptoms and behavior problems at 7 years. Results: Children (48% girls) spent a median (p25–p75) of 10 (10–11) hours per day sleeping, 1.5 (0.9–2) hours per day watching TV, 1.4 (0.9–1.9) hours per day engaging in cognitively stimulating activities, and 1.5 (0.4–2.3) hours per day engaging in physical activity. Longer sleep duration (>10 hours per day) was associated with a lower ADHD symptom score (adjusted incidence rate ratio = 0.97, 95% confidence interval, 0.95–1.00). Longer time spent in cognitively stimulating activities (>1 hours per day) was associated with lower scores of both ADHD symptoms (0.96, 0.94–0.98) and behavior problems (0.89, 0.83–0.97). Time spent watching TV and engaging in physical activity were not associated with either outcomes. Conclusion: A shorter sleep duration and less time spent in cognitively stimulating activities were associated with an increased risk of developing ADHD symptoms and behavior problems.

BACKGROUND: Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure. OBJECTIVE: We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school. METHODS: We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across 100-m buffers around all residential addresses since birth to estimate each participant's lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory (d' from computerized n-back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores. RESULTS: Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness. CONCLUSION: Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876. The research leading to these results received funding from the European Community’s Seventh Framework Program (ERCAdvanced Grant) under grant agreement number 268479: The BREATHE project. The research leading to the methodology used for the exposure assessment in this study received funding from the European Community’s Seventh Framework Program (FP7/2007-2013) under grant agreement number 282996: The PHENOTYPE project. P.D. is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness. The sponsors and funding organizations had no role in the design or conduct of this research.

C.T. is a recipient of a European Respiratory Society Fellowship (RESPIRE2–2015–7251) P.D. is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness. S.L. is funded by a Miguel Servet-FEDER fellowship (MS15/0025) awarded by the Spanish Ministry of Economy and Competitiveness. M.G. is funded by a Miguel Servet-FEDER fellowship (MS13/00054) awarded by the Spanish Ministry of Economy and Competitiveness, Dadvand, P., Tischer, C., Estarlich, M., Llop, S., Dalmau-Bueno, A., López-Vicente, M., Valentín, A., de Keijzer, C., Fernández-Somoano, A., Lertxundi, N., Rodriguez-Dehli, C., Gascon, M., Guxens, M., Zugna, D., Basagaña, X., Nieuwenhuijsen, M.J., Ibarluzea, J., Ballester, F., Sunyer, J.

Introduction Recently, we showed that exposure to traffic-related air pollutants (TRAPs) at school was negatively associated with cognitive development, specifically working memory and inattentiveness, in primary schoolchildren during a course of 12 months. The persistence of such associations over longer periods remains as an open question. Objective To study the longitudinal association between TRAPs at school and cognitive development over a period of 3.5 years. Methods Indoor and outdoor levels of TRAPs (elemental carbon (EC), dioxide nitrogen (NO 2 ), particulate matter (PM 2.5 ) from traffic sources and ultrafine particles (UFP)) were measured at 39 schools across Barcelona during 2012/2013. Working memory, as a measure of cognitive development, was evaluated 4 times in 2012/2013 assessment and was re-evaluated one more time in 2015 using computerized n-back test (3-back d′ as main outcome). Linear mixed effects models were used to test the association between TRAPs and 3-back d′, adding child and school as random effects to account for the multilevel nature of the data, and school air pollutants levels (one at a time) as predictor. Results We found detrimental associations between all TRAPs and annual change in 3-back d′ (working memory) (i.e. slower development of working memory in children attending schools with higher levels of air pollution). The associations (per one interquartile range increase in exposure) were strongest for outdoor NO 2 (Coefficient (Coef) = − 4.22, 95% confidence interval (CI), − 6.22, − 2.22) and indoor UFP (Coef = − 4.12, 95%CI, − 5.68, − 1.83). These reductions were equivalent to − 20% (95%CI, − 30.1, − 10.7) and − 19.9% (95%CI, − 31.5, − 8.4) change in annual working memory development associated with one interquartile range increase in outdoor NO 2 and indoor UFP, respectively. Conclusion Our findings suggest the persistence of the negative association between TRAPs exposure at school and cognitive trajectory measured by n-back test over a period of 3.5 years.

Background: The available evidence of the effects of air pollution and noise on behavioral development is limited, and it overlooks exposure at schools, where children spend a considerable amount of time. Objective: We aimed to investigate the associations of exposure to traffic-related air pollutants (TRAPs) and noise at school on behavioral development of schoolchildren. Methods: We evaluated children 7–11 years of age in Barcelona (Catalonia, Spain) during 2012–2013 within the BREATHE project. Indoor and outdoor concentrations of elemental carbon (EC), black carbon (BC), and nitrogen dioxide (NO2) were measured at schools in two separate 1-week campaigns. In one campaign we also measured noise levels inside classrooms. Parents filled out the strengths and difficulties questionnaire (SDQ) to assess child behavioral development, while teachers completed the attention deficit/hyperactivity disorder criteria of the DSM-IV (ADHD-DSM-IV) list to assess specific ADHD symptomatology. Negative binomial mixed-effects models were used to estimate associations between the exposures and behavioral development scores. Results: Interquartile range (IQR) increases in indoor and outdoor EC, BC, and NO2 concentrations were positively associated with SDQ total difficulties scores (suggesting more frequent behavioral problems) in adjusted multivariate models, whereas noise was significantly associated with ADHD-DSM-IV scores. Conclusion: In our study population of 7- to 11-year-old children residing in Barcelona, exposure to TRAPs at school was associated with increased behavioral problems in schoolchildren. Noise exposure at school was associated with more ADHD symptoms. Citation: Forns J, Dadvand P, Foraster M, Alvarez-Pedrerol M, Rivas I, López-Vicente M, Suades-Gonzalez E, Garcia-Esteban R, Esnaola M, Cirach M, Grellier J, Basagaña X, Querol X, Guxens M, Nieuwenhuijsen MJ, Sunyer J. 2016. Traffic-related air pollution, noise at school, and behavioral problems in Barcelona schoolchildren: a cross-sectional study. Environ Health Perspect 124:529–535; http://dx.doi.org/10.1289/ehp.1409449

Background: A few studies have reported associations between traffic-related air pollution exposure at schools and cognitive development. The role of PM components or sources other than traffic on cognitive development has been little explored. Objectives: We aimed to explore the role of PM sources in school air on cognitive development. Methods: A cohort of 2,618 schoolchildren (average age, 8.5 years) belonging to 39 schools in Barcelona (Spain) was followed up for a year. Children completed computerized tests assessing working memory, superior working memory, and inattentiveness during four visits. Particulate matter ≤ 2.5 μm (PM2.5) was measured during two 1-week campaigns in each school, both outdoors and in the classroom. Source apportionment resulted in nine sources: mineral, organic/textile/chalk, traffic, secondary sulfate and organics, secondary nitrate, road dust, metallurgy, sea spray, and heavy oil combustion. Differences in cognitive growth trajectories were assessed with mixed models with age-by-source interaction terms. Results: An interquartile range increase in indoor traffic-related PM2.5 was associated with reductions in cognitive growth equivalent to 22% (95% CI: 2%, 42%) of the annual change in working memory, 30% (95% CI: 6%, 54%) of the annual change in superior working memory, and 11% (95% CI: 0%, 22%) of the annual change in the inattentiveness scale. None of the other PM2.5 sources was associated with adverse effects on cognitive development. Conclusions: Traffic was the only source of fine particles associated with a reduction in cognitive development. Reducing air pollution from traffic at primary schools may result in beneficial effects on cognition. © 2016, Public Health Services, US Dept of Health and Human Services. All rights reserved., This work was supported by the European Research Council (ERC; grant no. 268479: the BREATHE project). F.A. is beneficiary of the Juan de la Cierva postdoctoral grant (JCI-2012-13473) from the Spanish Ministry of Economy and Competitiveness.

Background 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. Methods and Findings 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. Conclusions Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development., In a prospective cohort study, Jordi Sunyer and colleagues examine the association between traffic-related air pollution and 12 month cognitive development trajectories in primary school children in Barcelona., Editors' Summary Background Human brain development is a complex and lengthy process. During pregnancy, the basic structures of the brain are formed, and the neural circuits that will eventually control movement, speech, memory, and other cognitive (thinking) functions, as well as the function of many organs, begin to be established. By the time of birth, the brain is about a quarter of its adult size, and the neural circuits that control vital bodily functions such as breathing are well developed. By contrast, the cerebral cortex—the brain region that is involved in thought and action—is poorly developed. Much of the development of the cerebral cortex happens during the first two years of life. For example, babies usually learn to crawl at about nine months. Other aspects of brain function take longer to develop. Thus, the cognitive functions that are essential for learning undergo considerable development between the ages of 6 and 10 years, and further brain changes occur during adolescence. Why Was This Study Done? Exposure to the air pollutants produced by the combustion of fossil fuels by vehicles during pregnancy or infancy has been associated with delays in cognitive development. Moreover, experiments in animals suggest that traffic-related air pollution is a developmental neurotoxicant—a factor that disrupts brain development. However, although many schools are located next to busy roads and although traffic-related air pollution levels peak during school hours, it is not known whether exposure of school-age children to traffic-related air pollutants impairs their cognitive development and thus their ability to learn. Here, in a prospective cohort study (the BREATHE study), the researchers assess whether exposure of children aged 7–10 years to traffic-related air pollutants in schools in Barcelona, Spain, is associated with impaired cognitive development. A prospective cohort study is an observational investigation that studies groups (cohorts) of individuals who differ with respect to a specific factor to determine how exposure to this factor affects specific outcomes. What Did the Researchers Do and Find? The researchers used computerized tests to measure the development of working memory (the system that holds multiple pieces of transitory information in the mind where they can be manipulated), superior working memory (working memory that involves continuous updating of the working memory buffer), and attentiveness every three months over a 12-month period in 2,715 primary school children attending 39 schools exposed to high or low levels of traffic-related air pollution and paired by socioeconomic index. That is, the researchers compared three cognitive development outcomes in the children attending each school where exposure to air pollution was high with the same outcomes in children attending a school with a similar socioeconomic index where exposure to pollution was low; school pairing was undertaken to avoid “confounding” by social class, a factor that is known to affect cognitive development. Statistical analyses of these data indicated that the increase in cognitive development over time among children attending highly polluted schools was less than that among children attending paired lowly polluted schools, even after adjusting for additional factors that affect cognitive development. Thus, for example, there was an 11.5% 12-month increase in working memory at the lowly polluted schools but only a 7.4% 12-month increase in working memory at the highly polluted schools. Other analyses indicated that children attending schools with higher levels of traffic-related air pollutants in either the courtyard or in the classroom experienced a substantially smaller increase over the 12-month study in all three cognitive measurements than those attending schools with lower levels of pollutants. What Do These Findings Mean? These findings suggest that, compared with attendance at schools exposed to low levels of traffic-related air pollution, attendance at schools exposed to high levels of traffic-related air pollution is associated with a smaller increase in cognitive development over a 12-month period among 7- to 10-year-old children in Barcelona. The accuracy of these findings may be limited by residual confounding. That is, the children attending schools where traffic-related pollution is high might have shared other unknown characteristics that affected their cognitive development. Importantly, these findings do not prove that traffic-related air pollution causes impairment of cognitive development. Rather, they suggest that the developing brain may be vulnerable to traffic-related air pollution well into middle childhood, a conclusion that has implications for the design of air pollution regulations and for the location of new schools. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001792. The US Centers for Disease Control and Prevention provides information about child development, including information about middle childhood (in English and Spanish) Tox Town is an interactive site that provides information about toxic chemicals and environmental health risks, including air pollution The US Environmental Protection Agency provides information about air pollution near roadways and health Wikipedia has pages on cognitive development and on air pollution (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) MedlinePlus provides links to additional resources about air pollution (in English and Spanish) The Centre for Research in Environmental Epidemiology website provides more information about the BREATHE study

Objective To evaluate the role of extracurricular physical activity and sedentary behavior at preschool and primary school age on working memory at primary school age and adolescence, respectively. Study design This prospective study was based on a birth cohort across 4 Spanish regions. In the 3 younger subcohorts (n = 1093), parents reported lifestyle habits of child at age 4 years of age on a questionnaire, and children performed a computerized working memory task at 7 years of age. In the older subcohort (n = 307), the questionnaire was completed at 6 years of age and working memory was tested at 14 years of age. Adjusted regression models were developed to investigate the associations between lifestyle habits and working memory. Results Low extracurricular physical activity levels at 4 years of age were associated with a nonsignificant 0.95% (95% CI −2.81 to 0.92) reduction of correct responses in the working memory task at age 7 years of age. Low extracurricular physical activity levels at 6 years of age were associated with a 4.22% (95% CI −8.05 to −0.39) reduction of correct responses at age 14 years. Television watching was not associated with working memory. Other sedentary behaviors at 6 year of age were associated with a 5.07% (95% CI −9.68 to −0.46) reduction of correct responses in boys at 14 years of age. Conclusion Low extracurricular physical activity levels at preschool and primary school ages were associated with poorer working memory performance at primary school age and adolescence, respectively. High sedentary behavior levels at primary school age were related negatively to working memory in adolescent boys.

BACKGROUND: Neuropsychological instruments to assess cognitive trajectories during childhood in epidemiological studies are needed. This would improve neurodevelopment characterization in order to identify its potential determinants. We aimed to study whether repeated measures of n-back, a working memory task, detect developmental trajectories in schoolchildren during a 1-year follow-up. METHODS: We administered the n-back task to 2897 healthy children aged 7-11 years old from 39 schools in Barcelona (Spain). The task consisted of 2 levels of complexity or loads (2- and 3-back) and 2 different stimuli (numbers and words). Participants performed the task four times from January 2012 to March 2013. To study the trajectories during the follow-up, we performed linear mixed-effects models including school, individual and age as random effects. RESULTS: We observed improvements related to age in n-back outcomes d', HRT and accuracy, as well as reduced cognitive growth at older ages in d' and HRT. Greater improvements in performance were observed at younger ages, in 2-back, in verbal rather than numerical stimuli and in girls compared to boys. Boys responded faster at baseline, while girls showed increased growth in 2-back numbers. Children with ADHD (Attention Deficit and Hyperactivity Disorder) symptoms (15% of boys and 6% of girls) had a lower working memory at baseline, but they showed similar cognitive growth trajectories in numbers variants of the task, as compared to children without ADHD symptoms. However, the age-related improvement in response speed was not observed in children with ADHD symptoms. CONCLUSIONS: Changes in n-back outcomes reflected developmental trajectories in 1-year follow-up. The present results suggest that the repeated administration of this task can be used to study the factors that may alter the cognitive development during childhood.

A few studies have found associations between the exposure to traffic-related air pollution at school and/or home and cognitive development. The impact on cognitive development of the exposure to air pollutants during commuting has not been explored. We aimed to assess the role of the exposure to traffic-related air pollutants during walking commute to school on cognitive development of children. We performed a longitudinal study of children (n = 1,234, aged 7-10 y) from 39 schools in Barcelona (Catalonia, Spain) who commuted by foot to school. Children were tested four times during a 12-month follow-up to characterize their developmental trajectories of working memory (d' of the three-back numbers test) and inattentiveness (hit reaction time standard error of the Attention Network Test). Average particulate matter ≤2.5 μm (PM2.5), Black Carbon (BC) and NO2 concentrations were estimated using Land Use Regression for the shortest walking route to school. Differences in cognitive growth were evaluated by linear mixed effects models with age-by-pollutant interaction terms. Exposure to PM2.5 and BC from the commutes by foot was associated with a reduction in the growth of working memory (an interquartile range increase in PM2.5 and BC concentrations decreased the annual growth of working memory by 5.4 (95% CI [-10.2, -0.6]) and 4.6 (95% CI [-9.0, -0.1]) points, respectively). The findings for NO2 were not conclusive and none of the pollutants were associated with inattentiveness. Efforts should be made to implement pedestrian school pathways through low traffic streets in order to increase security and minimize children's exposure to air pollutants. The research leading to these results has received funding from the European Community's Seventh Framework Program (ERC-Advanced Grant) under grant agreement number 268479 - the BREATHE project

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. The research leading to these results has received funding from the European Community’s Seventh Framework Program (ERC-Advanced Grant) under grant 268479—the BREATHE project. It was also partly funded by the European Commission Seventh Framework Programme (grant 282996) for the PHENOTYPE (Positive Health Effects of the Natural Outdoor Environment in Typical /nPopulations in Different Regions in Europe) project. P.D. was funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness.

Graphical abstract, Highlights • 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., Background 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. Methods and findings 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. Conclusions 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.