Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (ß = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (ß = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (ß = -0.04; 95 %CI: -0.07, -0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Urban environment exposures, energy balance-related behaviors and their combination in preschoolers from three European countries.

BACKGROUND: Urban environments are characterized by many factors that may influence children's energy balance-related behaviors (EBRBs), but there is limited research on the impact of prospective exposure to multiple urban factors in preschoolers. We evaluated prospective associations between various urban exposures and EBRBs in preschoolers across Europe, with EBRBs considered both individually and combined into lifestyle patterns. METHODS: We used data from 4,073 preschoolers (aged 3-4 years) participating in three European cohorts from the EU Child Cohort Network: BiB (United Kingdom), EDEN (France), and INMA (Spain). Eighteen built and food environment, green spaces, road traffic and ambient air pollution exposures were characterized at residential addresses. Various EBRBs were considered as the outcomes including screen time, sleep duration and diet (fruit, vegetables, discretionary sweet foods, sweet beverages) individually and combined into unhealthy lifestyle patterns, using principal components analysis. Associations between urban exposures and outcomes were estimated using a single-exposure analysis and the deletion-substitution-addition algorithm was used to construct multi-exposure models. RESULTS: In multi-exposure models, greater walkability and smaller distance to the nearest road were associated with higher scores on the unhealthy lifestyle patterns. Likewise, greater walkability was associated with higher screen time and more frequent discretionary sweet food consumption. A smaller distance to the nearest road was also associated with lower sleep duration and more frequent sweet beverages consumption. On the other hand, higher levels of street connectivity showed an inverse association with the unhealthy lifestyle patterns. In the same vein, greater street connectivity was associated with decreased screen time. CONCLUSION: This comprehensive examination of multiple urban exposures indicates that residing in walkable environments and in close proximity to roads in densely-populated areas may not be advantageous for children EBRBs, while residing in neighborhoods with higher street connectivity appears to supposedly be beneficial.

Changes in prevalence and socioeconomic inequalities in secondhand smoke exposure in Spanish children, 2016-2019.

INTRODUCTION: Children are vulnerable to secondhand smoke (SHS) exposure, especially those with lower socioeconomic status. This study assesses the changes in prevalence and socioeconomic inequalities in SHS exposure in children younger than 12 years old in Spain between 2016 and 2019. METHODS: We conducted two cross-sectional studies among representative samples of households with children aged <12 years in Spain, in 2016 (n=2411) and 2019 (n=2412). Families were interviewed to assess children's SHS exposure in private settings and outdoor public venues and their adoption of home and car smoke-free rules. We used the education level of the home main earner as a proxy for socioeconomic position. Changes over time in the prevalence and socioeconomic inequalities of SHS exposure and smoke-free rules were estimated through adjusted Poisson regression models with robust variance according to sociodemographic covariates (adjusted prevalence ratios, APRs). RESULTS: In 2019, 70.5% of children were exposed to SHS in Spain. No changes between 2016 and 2019 were found for overall SHS exposure, exposure at home, and at school entrances. SHS exposure increased at public transport stations (APR=1.24; 95% CI: 1.03-1.49) and outdoor hospitality venues (APR=1.17; 95% CI: 1.07-1.29) while it decreased in cars (APR=0.74; 95% CI: 0.56-0.98) and parks (APR=0.87; 95% CI: 0.77-0.98). Households with lower education level had higher prevalence of SHS exposure at home in 2019 compared with those with university studies (primary: APR=1.30; 95% CI: 1.11-1.51; secondary: APR=1.12; 95% CI: 1.00-1.25) and were less likely to adopt home indoor smoke-free rules (primary: APR=0.88; 95% CI: 0.79-0.99; secondary: APR=0.95; 95% CI: 0.89-1.02). Socioeconomic inequalities in SHS exposure at home persisted between 2016 and 2019 (p>0.05), while decreased in smoke-free rules in cars (p=0.039). CONCLUSIONS: Reported SHS exposure among children in Spain remained high between 2016 and 2019. Inequalities persisted at home, highlighting the need for measures to reduce such exposure with an equity perspective.

Associations of gestational exposure to air pollution with maternal vitamin D levels: a meta-analysis.

OBJECTIVE: Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce. We investigated the association between air pollution during pregnancy and maternal vitamin D levels. METHODS: A total of 15,935 pregnant women from 5 birth cohorts in Europe and U.S were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants' residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception. RESULTS: We found an association between PM2.5 and higher odds of suboptimal vitamin D levels (i.e., below 20 ng/mL) (odds ratio per 5 µg/m3 increase in PM2.5, 1.43 95%CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels. CONCLUSIONS: PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.

Ambient air temperature exposure and foetal size and growth in three European birth cohorts.

INTRODUCTION: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. METHODS: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). RESULTS: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. CONCLUSIONS: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.

Nitrogen dioxide exposure, attentional function, and working memory in children from 4 to 8 years: Periods of susceptibility from pregnancy to childhood.

BACKGROUND: Air pollution exposure during pregnancy and childhood has been linked to executive function impairment in children, however, very few studies have assessed these two exposure periods jointly to identify susceptible periods of exposure. We sought to identify potential periods of susceptibility of nitrogen dioxide (NO2) exposure from conception to childhood on attentional function and working memory in school-aged children. METHODS: Within the Spanish INMA Project, we estimated residential daily NO2 exposures during pregnancy and up to 6 years of childhood using land use regression models (n = 1,703). We assessed attentional function at 4-6 years and 6-8 years, using the Conners Kiddie Continuous Performance Test and the Attention Network Test, respectively, and working memory at 6-8 years, using the N-back task. We used distributed lag non-linear models to assess the periods of susceptibility of each outcome, adjusting for potential confounders and correcting for multiple testing. We also stratified all models by sex. RESULTS: Higher exposure to NO2 between 1.3 and 1.6 years of age was associated with higher hit reaction time standard error (HRT-SE) (0.14 ms (95 % CI 0.05; 0.22) per 10 µg/m3 increase in NO2) and between 1.5 and 2.2 years of age with more omission errors (1.02 (95 % CI 1.01; 1.03) of the attentional function test at 4-6 years. Higher exposure to NO2 between 0.3 and 2.2 years was associated with higher HRT-SE (10.61 ms (95 % CI 3.46; 17.75) at 6-8 years only in boys. We found no associations between exposure to NO2 and working memory at 6-8 years. CONCLUSION: Our findings suggest that NO2 exposure during the first two years of life is associated with poorer attentional function in children from 4 to 8 years of age, especially in boys. These findings highlight the importance of exploring long-term effects of traffic-related air pollution exposure in older age groups.

The impact of prenatal mercury on neurobehavioral functioning longitudinally assessed from a young age to pre-adolescence in a Spanish birth cohort.

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. METHODS: The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. RESULTS: The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 µg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. CONCLUSION: Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted.

Pro-vegetarian dietary patterns and essential and heavy metal exposure in children of 4-5-years from the INfancia y medio Ambiente cohort (INMA).

Dietary patterns provide a comprehensive assessment of food consumption, including essential nutrients and potential exposure to environmental contaminants. While pro-vegetarian (PVG) dietary patterns have shown health benefits in adults, their effects on children are less well studied. This study aims to explore the association between children's adherence to the most common PVG dietary patterns and their exposure to metals, assessed through urine concentration. In our study, we included a population of 723 children aged 4-5-years from the INfancia y Medio Ambiente (INMA) cohort in Spain. We calculated three predefined PVG dietary patterns, namely general (gPVG), healthful (hPVG), and unhealthful (uPVG), using dietary information collected through a validated Food Frequency Questionnaire. Urinary concentrations of various essential and heavy metals (Co, Cu, Zn, Se, Mo, Pb, and Cd) were measured using mass spectrometry. Additionally, urinary arsenic speciation, including arsenobetaine (AsB), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and inorganic arsenic (iAs), was measured. The sum of urinary MMA and iAs was used to assess iAs exposure. We estimated primary (PMI) and secondary iAs methylation (SMI) indices. To explore the association between PVG dietary patterns in quintiles and metal exposure, we utilized multiple-adjusted linear regression models and the quantile g-computation approach. Compared with the lowest quintile, participants in the highest quintile of gPVG showed a 22.7% lower urinary Co (95% confidence interval (CI): -38.7; -1.98) and a 12.6% lower Se (95%CI: -22.9; -1.00) concentrations. Second quintile of adherence to hPVG was associated with a 51.7% lower urinary iAs + MMA concentrations (95%CI: -74.3; -8.61). Second quintile of adherence to an uPVG was associated with a 13.6% lower Se levels (95%CI: -22.9; -2.95) while the third quintile to this pattern was associated with 17.5% lower Mo concentrations (95%CI: -29.5; -2.95). The fourth quintile of adherence to gPVG was associated with a 68.5% higher PMI and a 53.7% lower SMI. Our study showed that adherence to a gPVG dietary pattern in childhood may modestly reduce the intakes of some essential metals such as Co and Se. Further investigations are warranted to explore any potential health implications.

Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Association of exposure to mixture of chemicals during pregnancy with cognitive abilities and fine motor function of children.

Chemical exposures often occur in mixtures and exposures during pregnancy may lead to adverse effects on the fetal brain, potentially reducing lower cognitive abilities and fine motor function of the child. We investigated the association of mothers exposure to a mixture of chemicals during pregnancy (i.e., organochlorine compounds, per- and polyfluoroalkyl substances, phenols, phthalates, organophosphate pesticides) with cognitive abilties and fine motor function in their children. We studied 1097 mother-child pairs from five European cohorts participating in the Human Early Life Exposome study (HELIX). Measurement of 26 biomarkers of exposure to chemicals was performed on urine or blood samples of pregnant women (mean age 31 years). Cognitive abilities and fine motor function were assessed in their children (mean age 8 years) with a battery of computerized tests administered in person (Ravens Coloured Progressive Matrices, Attention Network Test, N-back Test, Trail Making Test, Finger Tapping Test). We estimated the joint effect of prenatal exposure to chemicals on cognitive abilities and fine motor function using the quantile-based g-computation method, adjusting for sociodemographic characteristics. A quartile increase in all the chemicals in the overall mixture was associated with worse fine motor function, specifically lower scores in the Finger Tapping Test [-8.5 points, 95 % confidence interval (CI) -13.6 to -3.4; -14.5 points, 95 % CI -22.4 to -6.6, and -18.0 points, 95 % CI -28.6 to -7.4) for the second, third and fourth quartile of the overal mixture, respectively, when compared to the first quartile]. Organochlorine compounds, phthalates, and per- and polyfluoroalkyl substances contributed most to this association. We did not find a relationship with cognitive abilities. We conclude that exposure to chemical mixtures during pregnancy may influence neurodevelopment, impacting fine motor function of the offspring.

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

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

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

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

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

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

Association between residential exposure to road traffic noise and cognitive and motor function outcomes in children and preadolescents.

BACKGROUND: Exposure to environmental noise is increasing in recent years but most of the previous literature in children has evaluated the effect of aircraft noise exposure at schools on cognition. OBJECTIVE: To assess whether residential exposure to road traffic noise during pregnancy and childhood is associated with cognitive and motor function in children and preadolescents. METHODS: The study involved 619 participants from the Spanish INMA-Sabadell cohort and 7,115 from the Dutch Generation R Study. We used noise maps to estimate the average day-evening-night road traffic noise levels at each participant's residential address during pregnancy and childhood periods. Validated tests were administered throughout childhood in both cohorts to assess non-verbal and verbal intelligence, memory, processing speed, attentional function, working memory, cognitive flexibility, risky decision-making, and fine and gross motor function. Linear models, linear mixed models, and negative binomial models were run depending on the outcome in cohort-specific analysis and combined with a random-effects meta-analysis. All models were adjusted for several socioeconomic and lifestyle variables and results corrected for multiple testing. RESULTS: Average road traffic noise exposure levels during pregnancy and childhood were 61.3 (SD 6.0) and 61.5 (SD 5.4) dB for the INMA-Sabadell cohort and 54.6 (SD 7.9) and 53.5 (SD 6.5) dB for the Generation R Study, respectively. Road traffic noise exposure during pregnancy and childhood was not related to any of the cognitive and motor function outcomes examined in this study (e.g. -0.92 (95 % CI -2.08; 0.24) and 0.20 (95 % CI -0.96; 1.35) in overall estimates of memory and fine motor function, respectively, when road traffic noise increases by 10 dB during childhood). CONCLUSIONS: These findings suggest that child's cognitive or motor functions are not affected by residential exposure to road traffic noise. However, more studies evaluating this association at school and home settings as well as noise events are needed.

Relation of prenatal and postnatal PM2.5 exposure with cognitive and motor function among preschool-aged children.

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 µg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative ß (ßcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1-9 (ßcum = -2.55, 95%CrI = -3.53,-1.56) and on gross motor scores in weeks 7-17 (ßcum = -2.27,95%CrI = -3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (ßcum = -0.17, 95%CrI = -0.26,-0.09). In the postnatal period (from age 0.5-1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (ß = -2.42, 95%CrI = -3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.

Association between telomere length and neuropsychological function at 4-5 years in children from the INMA project: a cross-sectional study.

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4-5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children's Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (ß = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (ß = 3.85; 95% CI = -0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child's health, including cognitive functions such as working memory.

Childhood exposure to outdoor air pollution in different microenvironments and cognitive and fine motor function in children from six European cohorts.

BACKGROUND: Exposure to air pollution during childhood has been linked with adverse effects on cognitive development and motor function. However, limited research has been done on the associations of air pollution exposure in different microenvironments such as home, school, or while commuting with these outcomes. OBJECTIVE: To analyze the association between childhood air pollution exposure in different microenvironments and cognitive and fine motor function from six European birth cohorts. METHODS: We included 1301 children from six European birth cohorts aged 6-11 years from the HELIX project. Average outdoor air pollutants concentrations (NO2, PM2.5) were estimated using land use regression models for different microenvironments (home, school, and commute), for 1-year before the outcome assessment. Attentional function, cognitive flexibility, non-verbal intelligence, and fine motor function were assessed using the Attention Network Test, Trail Making Test A and B, Raven Colored Progressive Matrices test, and the Finger Tapping test, respectively. Adjusted linear regressions models were run to determine the association between each air pollutant from each microenvironment on each outcome. RESULTS: In pooled analysis we observed high correlation (rs = 0.9) between air pollution exposures levels at home and school. However, the cohort-by-cohort analysis revealed correlations ranging from low to moderate. Air pollution exposure levels while commuting were higher than at home or school. Exposure to air pollution in the different microenvironments was not associated with working memory, attentional function, non-verbal intelligence, and fine motor function. Results remained consistently null in random-effects meta-analysis. CONCLUSIONS: No association was observed between outdoor air pollution exposure in different microenvironments (home, school, commute) and cognitive and fine motor function in children from six European birth cohorts. Future research should include a more detailed exposure assessment, considering personal measurements and time spent in different microenvironments.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts.

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: - 1.27, 95% CI [- 2.22, - 0.32] / - 2.39, 95% CI [- 3.04, - 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: - 0.28, 95% CI [- 0.83, 0.27] / - 0.42, 95% CI [- 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Susceptible windows of prenatal and postnatal fine particulate matter exposures and attention-deficit hyperactivity disorder symptoms in early childhood.

Few prior studies have explored windows of susceptibility to fine particulate matter (PM2.5) in both the prenatal and postnatal periods and children's attention-deficit/hyperactivity disorder (ADHD) symptoms. We analyzed data from 1416 mother-child pairs from the Spanish INMA (INfancia y Medio Ambiente) Study (2003-2008). Around 5 years of age, teachers reported the number of ADHD symptoms (i.e., inattention, hyperactivity/impulsivity) using the ADHD Diagnostic and Statistical Manual of Mental Disorders. Around 7 years of age, parents completed the Conners' Parent Rating Scales, from which we evaluated the ADHD index, cognitive problems/inattention, hyperactivity, and oppositional subscales, reported as age- and sex-standardized T-scores. Daily residential PM2.5 exposures were estimated using a two-stage random forest model with temporal back-extrapolation and averaged over 1-week periods in the prenatal period and 4-week periods in the postnatal period. We applied distributed lag non-linear models within the Bayesian hierarchical model framework to identify susceptible windows of prenatal or postnatal exposure to PM2.5 (per 5-µg/m3) for ADHD symptoms. Models were adjusted for relevant covariates, and cumulative effects were reported by aggregating risk ratios (RRcum) or effect estimates (ßcum) across adjacent susceptible windows. A similar susceptible period of exposure to PM2.5 (1.2-2.9 and 0.9-2.7 years of age, respectively) was identified for hyperactivity/impulsivity symptoms assessed ~5 years (RRcum = 2.72, 95% credible interval [CrI] = 1.98, 3.74) and increased hyperactivity subscale ~7 years (ßcum = 3.70, 95% CrI = 2.36, 5.03). We observed a susceptibility period to PM2.5 on risk of hyperactivity/impulsivity symptoms ~5 years in gestational weeks 16-22 (RRcum = 1.36, 95% CrI = 1.22, 1.52). No associations between PM2.5 exposure and other ADHD symptoms were observed. We report consistent evidence of toddlerhood as a susceptible window of PM2.5 exposure for hyperactivity in young children. Although mid-pregnancy was identified as a susceptible period of exposure on hyperactivity symptoms in preschool-aged children, this association was not observed at the time children were school-aged.