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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. We aimed to investigate the associations of exposure to traffic-related air pollutants (TRAPs) and noise at school on behavioral development of schoolchildren. 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. 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. 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. 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.

Traffic-related exposures, such as air pollution and noise, show long-term associations with brain alterations in children and adolescents. The associations with functional connectivity have been studied using static approaches of resting-state functional magnetic resonance imaging (rs-fMRI) (i.e., average connectivity between regions across the scanning session). Our aim was to investigate the long-term association of traffic air pollution and noise during pregnancy and childhood with functional connectivity across adolescence using a dynamic approach, which captures different connectivity patterns across the scanning session. We used data from the Generation R population-based birth cohort. We estimated levels of 14 air pollutants and traffic noise at home addresses during pregnancy and childhood. We acquired rs-fMRI data at the age-10 y and age-14 y visits. We included participants with rs-fMRI data in at least one visit and either air pollution data ( ) or noise data ( ). We used k-means clustering to identify five connectivity patterns, called \"states,\" that reoccur over time and across subjects and visits. We calculated the mean time spent in each state for each participant and visit. We performed multi- and single-pollutant mixed effects models adjusted for socioeconomic and lifestyle variables, including the individual as random effect to test the associations between the exposures and the mean time spent in each state. Exposure to nitrogen oxides, particulate matter (PM), and road-traffic noise was related to differences in the time spent in the connectivity states, both in the multi- and single-pollutant models. For instance, higher levels of exposure to PM with aerodynamic diameter between and ( ) during pregnancy and higher noise exposure during childhood were associated with more time spent in a state in which the default-mode network, related to self-referential processes and mind-wandering, shows high connectivity. Traffic-related exposures might be related to long-term alterations in brain functional network organization in adolescents. Further research should explore the potential impact of these differences on cognition and psychopathology. https://doi.org/10.1289/EHP14525.

Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. General community. 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease. Child nonverbal and verbal IQ assessed at 1.5 to 8 years of age. There was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (-0.6 point; 95% CI: -1.7 to 0.4 points; P = 0.246) or lower verbal IQ (-0.6 point; 95% CI: -1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. Fetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.

Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log -transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log -unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log -unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log -unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log -unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data ( =640). Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062.

Abstract Context Low maternal free T4 (FT4) has been associated with poor child neurodevelopment in some single-center studies. Evidence remains scarce for the potential adverse effects of high FT4 and whether associations differ in countries with different iodine status. Objective To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. Design, Setting, and Participants Meta-analysis of individual participant data from 9036 mother–child pairs from three prospective population-based birth cohorts: INMA [Infancia y Medio Ambiente (Environment and Childhood project) (Spain)], Generation R (Netherlands), and ALSPAC (Avon Longitudinal Study of Parents and Children, United Kingdom). The exclusion criteria were multiple pregnancies, fertility treatments, thyroid-interfering medication usage, and known thyroid disease. Main Outcomes Child nonverbal IQ at 5 to 8 years of age, verbal IQ at 1.5 to 8 years of age, and autistic traits within the clinical range at 5 to 8 years of age. Results FT4 <2.5th percentile was associated with a 3.9-point (95% CI, −5.7 to −2.2) lower nonverbal IQ and a 2.1-point (95% CI, −4.0 to −0.1) lower verbal IQ. A suggestive association of hypothyroxinemia with a greater risk of autistic traits was observed. FT4 >97.5th percentile was associated with a 1.9-fold (95% CI, 1.0 to 3.4) greater risk of autistic traits. No independent associations were found with TSH. Conclusions Low maternal FT4 was consistently associated with a lower IQ across the cohorts. Further studies are needed to replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay. This study confirms that low FT4, but not TSH, during early pregnancy is associated with a lower IQ. We report a suggestive association of hypothyroxinemia and high maternal FT4 with autistic traits.

Background: Although it has been hypothesized that fetal exposure to endocrine-disrupting chemicals may increase obesity risk, empirical data are limited, and it is uncertain how early in life any effects may begin. Objectives: We explored whether prenatal exposure to several organochlorine compounds (OCs) is associated with rapid growth in the First 6 months of life and body mass index (BMI) later in infancy. Methods: Data come from the INMA (Infancia y Medio-Ambiente) Child and Environment birth cohort in Spain, which recruited 657 women in early pregnancy. Rapid growth during the first 6 months was defined as a change in weight-for-age z-scores > 0.67, and elevated BMI at 14 months, as a z-score ≥ the 85th percentile. Generalized linear models were used to estimate the risk of rapid growth or elevated BMI associated with 2,2-bis(p-chlorophenyl)-1, 1-dichloroethylene (DDE), hexachlorobenzene, β-hexachlorohexane, and polychlorinated biphenyls in first-trimester maternal serum. Results: After multivariable adjustment including other OCs, DDE exposure above the first quartile was associated with doubling of the risk of rapid growth among children of normal-weight (BMI < 25 kg/m²), but not overweight, mothers. DDE was also associated with elevated BMI at 14 months (relative risk per unit increase in log DDE = 1.50; 95% confidence interval, 1.11-2.03). Other OCs were not associated with rapid growth or elevated BMI after adjustment. Conclusions: In this study we found prenatal DDE exposure to be associated with rapid weight gain in the first 6 months and elevated BMI later in infancy, among infants of normal-weight mothers. More research exploring the potential role of chemical exposures in early-onset obesity is needed.

Background/objectivesA higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8.Subjects/methodsWe analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0–6), medium (7–10), and high (11–16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4–8 years of age.ResultsIn cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21–0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05–0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12–0.73; p = 0.008) at the age of 8.ConclusionThis study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood. According to a recent systematic review, the worldwide estimate of ADHD prevalence is 7.2% in children. This study aims to assess the prevalence of ADHD diagnoses in 2017 and the incidence of ADHD diagnoses in 2009–2017 in children living in Catalonia, Spain, as well as their temporal and geographical variability, and stratifying by sex and age. We used administrative data for all children aged 4 to 17 years who were insured in the public Catalan Health System in 2009–2017. We identified all ADHD cases diagnosed in 2009–2017 (ICD-9 code 314). We estimated the prevalence of ADHD diagnoses in 2017 and the overall annual incidence of ADHD diagnoses in 2009–2017. We used Poisson regression models to assess temporal trends in the incidence. We estimated a prevalence of ADHD diagnoses of 4.06% (95%CI 4.03, 4.10) in 2017, being 5.81% (95%CI 5.75, 5.87) for boys and 2.20% (95%CI 2.16, 2.24) for girls, the highest prevalence being in 13-to-17-year-olds (7.28% (95%CI 7.20, 7.36)). We did not observe a statistically significant increase of the incidence of ADHD diagnoses during the study period. Geographical differences were found across the healthcare areas in both prevalence and annual incidence and constant during the study period. In conclusion, the prevalence of ADHD diagnoses observed in this study was 4.06%, which was lower than the estimates reported in previous systematic reviews, but in line with the prevalence estimates from other recent European studies. The prevalence was higher in boys than girls, with a sex ratio consistent with previous studies. We did not observe an increase in the temporal trend of incidence of ADHD diagnoses in recent years, but we found geographical differences.

Prenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact. We aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight. Within the Generation R Study, a population-based cohort in Netherlands ( ), urinary concentrations of 11 phthalate metabolites, 3 bisphenols, and 5 dialkylphosphate (DAP) metabolites were measured at , 18-25, and of gestation and averaged. Ultrasound measures of head circumference, femur length, and estimated fetal weight (EFW) were taken at 18-25 and of gestation, and measurements of head circumference, length, and weight were performed at delivery. We estimated the difference in each fetal measurement per quartile increase in all exposures within the mixture with quantile g-computation. The average EFW at 18-25 wk and was 369 and , respectively, and the average birth weight was . Higher exposure was associated with smaller fetal and newborn growth parameters in a nonlinear fashion. At 18-25 wk, fetuses in the second, third, and fourth quartiles of exposure (Q2-Q4) had [ , ], ( , ), and ( , 1) lower EFW compared with those in the first quartile (Q1). A similar dose-response pattern was observed at , but all effect sizes were smaller, and no association was observed comparing Q4 to Q1. At birth, we observed no differences in weight between Q1-Q2 or Q1-Q3. However, fetuses in Q4 had ( , 76) lower birth weight in comparison with those in Q1. Results observed at 18-25 and were similar for femur length; however, no differences were observed at birth. No associations were observed for head circumference. Higher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial. https://doi.org/10.1289/EHP9178.

Prenatal life and childhood represent periods that are vulnerable to environmental exposures. Both cold and heat may have negative impacts on children’s mental health and cognition, but the underlying neural mechanisms are unknown. Here, by a magnetic resonance imaging assessment of 2,681 children from the Netherlands Generation R birth cohort, we show that heat exposure during infancy and toddlerhood as well as cold exposure during pregnancy and infancy are associated with higher mean diffusivity at preadolescence, indicative of reduced myelination and maturation of white matter microstructure. No associations for fractional anisotropy were observed. Children living in poorer neighbourhoods were more vulnerable to cold and heat exposure. Our findings suggest that cold and heat exposure in periods of rapid brain development may have lasting impacts on children’s white matter microstructure, a risk that must be considered in the context of ongoing climate change.Using magnetic resonance imaging assessment of 2,681 children from the Netherlands, the authors investigate effects of cold and heat exposure during pregnancy, infancy and childhood. They found that these exposures can have lasting impacts on white matter microstructure at preadolescence.