Joan Forns

Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4 years of age.

There are at present very few studies of the effects of polybromodiphenyl ethers (PBDEs), used as flame retardants in consumer products, on neurodevelopment or thyroid hormone levels in humans. The present study aims to examine the association between pre and postnatal PBDE concentrations and neurodevelopment and thyroid hormone levels in children at age 4years and isolate the effects of PBDEs from those of PCBs, DDT, DDE and HCB. A prospective birth cohort in Menorca (Spain) enrolled 482 pregnant mothers between 1997 and 1998. At 4years, children were assessed for motor and cognitive function (McCarthy Scales of Childrens Abilities), attention-deficit, hyperactivity and impulsivity (ADHD-DSM-IV) and social competence (California Preschool Social Competence Scale). PBDE concentrations were measured in cord blood (N=88) and in serum of 4years olds (N=244). Among all congeners analyzed only PBDE 47 was quantified in a reasonable number of samples (LOQ=0.002ng/ml). Exposure to PBDE 47 was analyzed as a dichotomous variable: concentrations above the LOQ (exposed) and concentrations below (referents). Scores for cognitive and motor functions were always lower in children pre and postnatally exposed to PBDE47 than in referents, but none of these associations was statistically significant (β coefficient (95%CI) of the total cognition score: -2.7 (-7.0, 1.6) for postnatal exposure, and -1.4 (-9.2, 6.5) for prenatal exposure). Postnatal exposure to PBDE 47 was statistically significantly related to an increased risk of symptoms on the attention deficit subscale of ADHD symptoms (RR (95%CI)=1.8 (1.0, 3.2)) but not to hyperactivity symptoms. A statistically significant higher risk of poor social competence symptoms was observed as a consequence of postnatal PBDE 47 exposure (RR (95%CI)=2.6 (1.2, 5.9)). Adjustment for other organochlorine compounds did not influence the results. Levels of thyroid hormones were not associated to PBDE exposure. This study highlights the importance of assessing the effects of PBDE exposure not just prenatally but also during the early years of life. In the light of current evidence a precautionary approach towards PBDE exposure of both mothers and children seems warranted.

Mental Health Benefits of Long-Term Exposure to Residential Green and Blue Spaces: A Systematic Review

Many studies conducted during the last decade suggest the mental health benefits of green and blue spaces. We aimed to systematically review the available literature on the long-term mental health benefits of residential green and blue spaces by including studies that used standardized tools or objective measures of both the exposures and the outcomes of interest. We followed the PRISMA statement guidelines for reporting systematic reviews and meta-analysis. In total 28 studies were included in the systematic review. We found limited evidence for a causal relationship between surrounding greenness and mental health in adults, whereas the evidence was inadequate in children. The evidence was also inadequate for the other exposures evaluated (access to green spaces, quality of green spaces, and blue spaces) in both adults and children. The main limitation was the limited number of studies, together with the heterogeneity regarding exposure assessment. Given the increase in mental health problems and the current rapid urbanization worldwide, results of the present systematic review should be taken into account in future urban planning. However, further research is needed to provide more consistent evidence and more detailed information on the mechanisms and the characteristics of the green and blue spaces that promote better mental health. We provide recommendations for future studies in order to provide consistent and evidence-based recommendations for policy makers.

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.

Polybrominated diphenyl ethers (PBDEs) in breast milk and neuropsychological development in infants

Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children’s neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209.

Thyroxine levels during pregnancy in healthy women and early child neurodevelopment.

Background: The fetus depends on maternal thyroid hormones during pregnancy for normal brain development. Little is known about the effects of subclinical hypothyroidism and mild hypothyroxinemia during pregnancy on neurodevelopment of the child. Methods: We evaluated a population-based birth cohort in Spain. A total of 1761 children and their mothers were included in the main analyses. Serum levels of free thyroxine and thyrotropin were measured in pregnant women. Mental and psychomotor development of their children was assessed using the Bayley Scales of Infant Development during the second year of life. Results: Low free thyroxine levels (<5th percentile) and self-reported prepregnancy thyroid disorder without medical treatment were associated with a decrease of mental scores (Beta = −3.4 [95% confidence interval= −6.7 to −0.2]) and −5.5 [−8.9 to −2.0], respectively). No association between thyrotropin levels and mental scores or psychomotor scores was observed. Conclusions: Low free thyroxine levels in healthy pregnant women are related to a moderate delay in child neurodevelopment. The impairment is similar in magnitude to that observed in mothers with untreated prepregnancy thyroid disorder. The value of screening pregnant women for thyroid function requires further assessment, particularly in mildly iodine-deficient areas.

Genetic Variants of the FADS Gene Cluster and ELOVL Gene Family, Colostrums LC-PUFA Levels, Breastfeeding, and Child Cognition

Introduction Breastfeeding effects on cognition are attributed to long-chain polyunsaturated fatty acids (LC-PUFAs), but controversy persists. Genetic variation in fatty acid desaturase (FADS) and elongase (ELOVL) enzymes has been overlooked when studying the effects of LC-PUFAs supply on cognition. We aimed to: 1) to determine whether maternal genetic variants in the FADS cluster and ELOVL genes contribute to differences in LC-PUFA levels in colostrum; 2) to analyze whether these maternal variants are related to child cognition; and 3) to assess whether childrens variants modify breastfeeding effects on cognition. Methods Data come from two population-based birth cohorts (n = 400 mother-child pairs from INMA-Sabadell; and n = 340 children from INMA-Menorca). LC-PUFAs were measured in 270 colostrum samples from INMA-Sabadell. Tag SNPs were genotyped both in mothers and children (13 in the FADS cluster, 6 in ELOVL2, and 7 in ELOVL5). Child cognition was assessed at 14 mo and 4 y using the Bayley Scales of Infant Development and the McCarthy Scales of Childrens Abilities, respectively. Results Children of mothers carrying genetic variants associated with lower FADS1 activity (regulating AA and EPA synthesis), higher FADS2 activity (regulating DHA synthesis), and with higher EPA/AA and DHA/AA ratios in colostrum showed a significant advantage in cognition at 14 mo (3.5 to 5.3 points). Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. Moreover, not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele. Conclusion Genetically determined maternal supplies of LC-PUFAs during pregnancy and lactation appear to be crucial for child cognition. Breastfeeding effects on cognition are modified by child genetic variation in fatty acid desaturase and elongase enzymes.

Breastfeeding, Long-Chain Polyunsaturated Fatty Acids in Colostrum, and Infant Mental Development

BACKGROUND: Breastfeeding has been associated with improved neurodevelopment in children. However, it remains unknown to what extent nutritional advantages of breast milk may explain this relationship. OBJECTIVE: We assessed the role of parental psychosocial factors and colostrum long-chain polyunsaturated fatty acid (LC-PUFA) levels in the relationship between breastfeeding and childrens neurodevelopment. METHODS: A population-based birth cohort was established in the city of Sabadell (Catalonia, Spain) as part of the INMA-INfancia y Medio Ambiente Project. A total of 657 women were recruited during the first trimester of pregnancy. Information about parental characteristics and breastfeeding was obtained by using a questionnaire, and trained psychologists assessed mental and psychomotor development by using the Bayley Scales of Infant Development in 504 children at 14 months of age. RESULTS: A high percentage of breastfeeds among all milk feeds accumulated during the first 14 months was positively related with child mental development (0.37 points per month of full breastfeeding [95% confidence interval: 0.06–0.67]). Maternal education, social class, and intelligence quotient only partly explained this association. Children with a longer duration of breastfeeding also exposed to higher ratios between n-3 and n-6 PUFAs in colostrum had significantly higher mental scores than children with low breastfeeding duration exposed to low levels. CONCLUSIONS: Greater levels of accumulated breastfeeding during the first year of life were related to higher mental development at 14 months, largely independently from a wide range of parental psychosocial factors. LC-PUFA levels seem to play a beneficial role in childrens mental development when breastfeeding levels are high.

Green and blue spaces and behavioral development in Barcelona schoolchildren: 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. Citation: Amoly E, Dadvand P, Forns J, López-Vicente M, Basagaña X, Julvez J, Alvarez-Pedrerol M, Nieuwenhuijsen MJ, Sunyer J. 2014. Green and blue spaces and behavioral development in Barcelona schoolchildren: the BREATHE Project. Environ Health Perspect 122:1351–1358; http://dx.doi.org/10.1289/ehp.1408215

Air pollution during pregnancy and childhood cognitive and psychomotor development: six European birth cohorts.

Background: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. Methods: We analyzed data from 6 European population-based birth cohorts—GENERATION R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)—that recruited mother–infant pairs from 1997 to 2008. Air pollution levels—nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5–10 &mgr;m (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup—at birth addresses were estimated by land-use regression models, based on monitoring campaigns performed primarily between 2008 and 2011. Levels were back-extrapolated to exact pregnancy periods using background monitoring sites. Cognitive and psychomotor development was assessed between 1 and 6 years of age. Adjusted region-specific effect estimates were combined using random-effects meta-analysis. Results: A total of 9482 children were included. Air pollution exposure during pregnancy, particularly NO2, was associated with reduced psychomotor development (global psychomotor development score decreased by 0.68 points [95% confidence interval = −1.25 to −0.11] per increase of 10 &mgr;g/m3 in NO2). Similar trends were observed in most regions. No associations were found between any air pollutant and cognitive development. Conclusions: Air pollution exposure during pregnancy, particularly NO2 (for which motorized traffic is a major source), was associated with delayed psychomotor development during childhood. Due to the widespread nature of air pollution exposure, the public health impact of the small changes observed at an individual level could be considerable.