Mikel Esnaola

Green spaces and cognitive development in primary schoolchildren

Significance Green spaces have a range of health benefits, but little is known in relation to cognitive development in children. This study, based on comprehensive characterization of outdoor surrounding greenness (at home, school, and during commuting) and repeated computerized cognitive tests in schoolchildren, found an improvement in cognitive development associated with surrounding greenness, particularly with greenness at schools. This association was partly mediated by reductions in air pollution. Our findings provide policymakers with evidence for feasible and achievable targeted interventions such as improving green spaces at schools to attain improvements in mental capital at population level. Exposure to green space has been associated with better physical and mental health. Although this exposure could also influence cognitive development in children, available epidemiological evidence on such an impact is scarce. This study aimed to assess the association between exposure to green space and measures of cognitive development in primary schoolchildren. This study was based on 2,593 schoolchildren in the second to fourth grades (7–10 y) of 36 primary schools in Barcelona, Spain (2012–2013). Cognitive development was assessed as 12-mo change in developmental trajectory of working memory, superior working memory, and inattentiveness by using four repeated (every 3 mo) computerized cognitive tests for each outcome. We assessed exposure to green space by characterizing outdoor surrounding greenness at home and school and during commuting by using high-resolution (5 m × 5 m) satellite data on greenness (normalized difference vegetation index). Multilevel modeling was used to estimate the associations between green spaces and cognitive development. We observed an enhanced 12-mo progress in working memory and superior working memory and a greater 12-mo reduction in inattentiveness associated with greenness within and surrounding school boundaries and with total surrounding greenness index (including greenness surrounding home, commuting route, and school). Adding a traffic-related air pollutant (elemental carbon) to models explained 20–65% of our estimated associations between school greenness and 12-mo cognitive development. Our study showed a beneficial association between exposure to green space and cognitive development among schoolchildren that was partly mediated by reduction in exposure to air pollution.

Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study.

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.

A Common 16p11.2 Inversion Underlies the Joint Susceptibility to Asthma and Obesity

The prevalence of asthma and obesity is increasing worldwide, and obesity is a well-documented risk factor for asthma. The mechanisms underlying this association and parallel time trends remain largely unknown but genetic factors may be involved. Here, we report on a common ~0.45 Mb genomic inversion at 16p11.2 that can be accurately genotyped via SNP array data. We show that the inversion allele protects against the joint occurrence of asthma and obesity in five large independent studies (combined sample size of 317 cases and 543 controls drawn from a total of 5,809 samples; combined OR = 0.48, p = 5.5 × 10(-6)). Allele frequencies show remarkable worldwide population stratification, ranging from 10% in East Africa to 49% in Northern Europe, consistent with discordant and extreme genetic drifts or adaptive selections after human migration out of Africa. Inversion alleles strongly correlate with expression levels of neighboring genes, especially TUFM (p = 3.0 × 10(-40)) that encodes a mitochondrial protein regulator of energy balance and inhibitor of type 1 interferon, and other candidates for asthma (IL27) and obesity (APOB48R and SH2B1). Therefore, by affecting gene expression, the ~0.45 Mb 16p11.2 inversion provides a genetic basis for the joint susceptibility to asthma and obesity, with a population attributable risk of 39.7%. Differential mitochondrial function and basal energy balance of inversion alleles might also underlie the potential selection signature that led to their uneven distribution in world populations.

Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consumption Levels

Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype. We evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004-2008. Bayley and McCarthy scales and the Childhood Asperger Syndrome Test were used to assess neuropsychological development. Results from multivariate linear regression models were adjusted for sociodemographic characteristics and further adjusted for umbilical cord blood mercury or long-chain polyunsaturated fatty acid concentrations. Overall, consumption of seafood above the recommended limit of 340 g/week was associated with 10-g/week increments in neuropsychological scores. By subtype, in addition to lean fish, consumption of large fatty fish showed a positive association; offspring of persons within the highest quantile (>238 g/week) had an adjusted increase of 2.29 points in McCarthy general cognitive score (95% confidence interval: 0.42, 4.16). Similar findings were observed for the Childhood Asperger Syndrome Test. Beta coefficients diminished 15%-30% after adjustment for mercury or long-chain polyunsaturated fatty acid concentrations. Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits.

Traffic-Related air pollution, noise at school, and behavioral problems in barcelona schoolchildren: A cross-sectional study

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

A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments

BackgroundHigh-throughput RNA sequencing (RNA-seq) offers unprecedented power to capture the real dynamics of gene expression. Experimental designs with extensive biological replication present a unique opportunity to exploit this feature and distinguish expression profiles with higher resolution. RNA-seq data analysis methods so far have been mostly applied to data sets with few replicates and their default settings try to provide the best performance under this constraint. These methods are based on two well-known count data distributions: the Poisson and the negative binomial. The way to properly calibrate them with large RNA-seq data sets is not trivial for the non-expert bioinformatics user.ResultsHere we show that expression profiles produced by extensively-replicated RNA-seq experiments lead to a rich diversity of count data distributions beyond the Poisson and the negative binomial, such as Poisson-Inverse Gaussian or Pólya-Aeppli, which can be captured by a more general family of count data distributions called the Poisson-Tweedie. The flexibility of the Poisson-Tweedie family enables a direct fitting of emerging features of large expression profiles, such as heavy-tails or zero-inflation, without the need to alter a single configuration parameter. We provide a software package for R called tweeDEseq implementing a new test for differential expression based on the Poisson-Tweedie family. Using simulations on synthetic and real RNA-seq data we show that tweeDEseq yields P-values that are equally or more accurate than competing methods under different configuration parameters. By surveying the tiny fraction of sex-specific gene expression changes in human lymphoblastoid cell lines, we also show that tweeDEseq accurately detects differentially expressed genes in a real large RNA-seq data set with improved performance and reproducibility over the previously compared methodologies. Finally, we compared the results with those obtained from microarrays in order to check for reproducibility.ConclusionsRNA-seq data with many replicates leads to a handful of count data distributions which can be accurately estimated with the statistical model illustrated in this paper. This method provides a better fit to the underlying biological variability; this may be critical when comparing groups of RNA-seq samples with markedly different count data distributions. The tweeDEseq package forms part of the Bioconductor project and it is available for download at http://www.bioconductor.org.

Neurodevelopmental deceleration by urban fine particles from different emission sources: A longitudinal observational study

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. Citation: Basagaña X, Esnaola M, Rivas I, Amato F, Alvarez-Pedrerol M, Forns J, López-Vicente M, Pujol J, Nieuwenhuijsen M, Querol X, Sunyer J. 2016. Neurodevelopmental deceleration by urban fine particles from different emission sources: a longitudinal observational study. Environ Health Perspect 124:1630–1636; http://dx.doi.org/10.1289/EHP209

Spatiotemporally resolved black carbon concentration, schoolchildren's exposure and dose in Barcelona

Abstract At city level, personal monitoring is the best way to assess peoples exposure. However, it is usually estimated from a few monitoring stations. Our aim was to determine the exposure to black carbon (BC) and BC dose for 45 schoolchildren with portable microaethalometers and to evaluate the relationship between personal monitoring and fixed stations at schools (indoor and outdoor) and in an urban background (UB) site. Personal BC concentra‐tions were 20% higher than in fixed stations at schools. Linear mixed‐effect models showed low R 2 between personal measurements and fixed stations at schools (R 2 ≤ 0.28), increasing to R 2 ≥ 0.70 if considering only periods when children were at schools. For the UB station, the respective R 2 were 0.18 and 0.45, indicating the importance of the distance to the monitoring station when assessing exposure. During the warm season, the fixed stations agreed better with personal measurements than during the cold one. Children spent 6% of their time on commuting but received 20% of their daily BC dose, due to co‐occurrence with road traffic rush hours and the close proximity to the source. Children received 37% of their daily‐integrated BC dose at school. Indoor environments (classroom and home) were responsible for the 56% BC dose.

Developmental Trajectories in Primary Schoolchildren Using n-Back Task

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.

Green spaces and spectacles use in schoolchildren in Barcelona.

Abstract Myopia is one of the major causes of low visual acuity during childhood, and hence of the need for spectacles. It is generally more prevalent in urban areas where children are often less exposed to green spaces than in rural areas. This study evaluated the association between exposure to green space and use of spectacles (as a surrogate measure for myopia) in a cohort of 2727 schoolchildren (7–10 years old) recruited from 39 primary schools in Barcelona (2012–2015). We assessed exposure to green spaces by characterizing outdoor surrounding greenness at home and school and during commuting using satellite data on greenness (Normalized Difference Vegetation Index). We also obtained data on the annual average time children spent playing in green spaces through questionnaires. Cross‐sectional analyses were conducted based on prevalent cases of spectacles use at baseline data collection campaign and longitudinal analyses based on incident cases of spectacles use during the three‐year period between the baseline and last data collection campaigns. An interquartile range (IQR) increase in exposure to green space at home (500 m buffer) and school and during commuting was associated with respectively 14% (95% CI: 2%, 26%), 27% (95% CI: 6%, 44%), and 20% (95% CI: 5%, 33%) decrease in spectacles use in cross‐sectional analyses. In longitudinal analyses, we observed a reduction of 23% (95% CI: 4%, 39%) and 34% (95% CI: 2%, 55%) associated with an IQR increase in greenness at home and school, respectively. Moreover, an IQR increase in time playing in green spaces was associated with a 28% (95% CI: 7%, 45%) reduction in the risk of spectacles use in the longitudinal analysis. Our observed reduced risk of spectacles use associated with higher contact with green space calls for more refined studies of the association between green spaces and refractive errors of visions. HighlightsThe cause(s) of rapid increase in the global prevalence of myopia is unclear.Myopia is consistently reported to be more prevalent in urban areas.Urban residents often have limited access to green spaces.Higher greenness exposure was associated with lower spectacles use in children.Our findings require further confirmation by more refined studies.