Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4years 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 4. years 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 4. years, children were assessed for motor and cognitive function (McCarthy Scales of Children's 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 4. years olds (N = 244). Among all congeners analyzed only PBDE 47 was quantified in a reasonable number of samples (LOQ = 0.002. ng/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. © 2010 Elsevier Ltd

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

Traffic-related air pollution, APOE ∊4 status, and neurodevelopmental outcomes among school children enrolled in the BREATHE project (Catalonia, spain)

BACKGROUND: Traffic-related air pollution is emerging as a risk factor for Alzheimer's disease (AD) and impaired brain development. Individual differences in vulnerability to air pollution may involve the e4 allele of Apolipoprotein E (APOE) gene, the primary genetic risk factor for AD. OBJECTIVE: We analyzed whether the association between traffic air pollution and neurodevelopmental outcomes is modified by APOE e4 status in children. METHODS: Data on parent-reported behavior problems (total difficulties scores, Strengths and Difficulties Questionnaire), teacher-reported attention-deficit hyperactivity disorder (ADHD) symptom scores, cognitive performance trajectories (computerized tests of inattentiveness and working memory repeated 2–4 times during January 2012–March 2013), and APOE genotypes were obtained for 1,667 children age 7–11 y attending 39 schools in or near Barcelona. Basal ganglia volume (putamen, caudate, and globus pallidum) was measured in 163 of the children by MRI (October 2012–April 2014.) Average annual outdoor polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC), and nitrogen dioxide (NO ) concentrations were estimated based on measurements at each school (two 1-wk campaigns conducted 6 months apart in 2012). RESULTS: APOE e4 allele carriers had significantly higher behavior problem scores than noncarriers, and adverse associations with PAHs and NO were stronger or limited to e4 carriers for behavior problem scores (P-interaction 0.03 and 0.04), caudate volume (P-interaction 0.04 and 0.03), and inattentiveness trajectories (P-interaction 0.15 and 0.08, respectively). Patterns of associations with the same outcomes were similar for EC. CONCLUSION: PAHs, EC, and NO were associated with higher behavior problem scores, smaller reductions in inattentiveness over time, and smaller caudate volume in APOE e4 allele carriers in our study population, and corresponding associations were weak or absent among e4 noncarriers. These findings support a potential role of APOE in biological mechanisms that may contribute to associations between air pollution and neurobehavioral outcomes in children

Green spaces and cognitive development in primary schoolchildren

© 2015, National Academy of Sciences. All rights reserved. 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 x5 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

Air Pollution Exposure during Pregnancy and Childhood Autistic Traits in Four European Population-Based Cohort Studies: The ESCAPE Project

Background: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. Objectives: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. Methods: Ours was a collaborative study of four European population-based birth/child cohorts—CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. Results: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. Conclusions: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies.Funding was provided as follows: ESCAPE Project— European Community’s Seventh Framework Program (FP7/2007-2011-GA#211250). CATSS, Sweden— Swedish Research Council for Health, Working Life and Welfare (FORTE), Swedish Research Council (VR) Formas, in partner hip with FORTE and VINNOVA (cross-disciplinary research program concerning children’s and young people’s mental health); VR through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant 340-2013-5867; HKH Kronprinsessan Lovisas förening för barnasjukvård; and the Strategic Research Program in Epidemiology at Karolinska Institutet. Generation R, the Netherlands—The Generation R Study is conducted by the Erasmus University Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus University Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The Netherlands Organisation for Applied Scientific Research (TNO) received funding from the Netherlands Ministry of Infrastructure and the Environment to support exposure assessment. GASPII, Italy—grant from the Italian Ministry of Health (ex art.12, 2001). INMA, Spain— grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041 FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI041436, FIS-PI081151, FIS-PI06/0867, FIS-PS09/00090), PI13/1944, PI13_02032, PI14/0891, PI14/1687, MS13/00054, UE (FP7-ENV-2011 cod 282957, and HEALTH.2010.2.4.5-1); Generalitat de Catalunya-CIRIT 1999SGR 00241; La Fundació La Marató de TV3 (090430); Conselleria de Sanitat Generalitat Valenciana; Department of Health of the Basque Government (2005111093 and 2009111069); and Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). V.W.V.J. received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw 90700303, 916.10159). A.G.’s work was supported by a research grant from the European Community’s 7th Framework Programme (FP7/2008–2013-GA#212652). A full roster of the INMA project investigators can be found online (http://www. proyectoinma.org/presentacion-inma/listado-investigadores/ en_listado-investigadores.html)

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 children's 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 Children"s 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

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 children's 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 Children"s 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

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

Increased risk of falls and fractures in patients with psychosis and Parkinson disease.

ObjectiveEvaluate whether the risk of falls and fractures differs between patients with Parkinson disease with psychosis (PDP) and patients with Parkinson disease (PD) without psychosis at similar disease stages.MethodsPatients with PD without psychosis were identified in the Medicare claims databases (2008-2018) and followed from the first PD diagnosis date during the study period. Patients with a subsequent diagnosis of psychosis were included in the PDP group. Patients with PDP and PD without psychosis were propensity score-matched based on characteristics within blocks of time since cohort entry. The incidence rates (IRs), expressed per 100 person-years, and 95% confidence intervals (CIs) of falls and fractures were evaluated as composite and separate outcomes. Incidence rate ratios (IRRs) were used to compare patients with PDP and PD without psychosis in the matched cohort.Results154,306 patients had PD without psychosis and no falls or fractures before cohort entry; the IR for falls and fractures was 11.41 events (95% CI, 11.29-11.53). 12,127 patients (7.8%) had a subsequent PDP diagnosis. PDP patients had a higher prevalence of most comorbidities and risk factors for falls and fractures than those without psychosis. The crude IR for falls and fractures among PDP patients was 29.03 events (95% CI, 28.27-29.81). PD without psychosis and PDP groups had more falls than fractures. After matching, 24,144 PD patients without psychosis (15.6%) and 12,077 PDP patients (99.6%) were retained. Matched PDP patients had a higher incidence of falls and fractures than PD patients without psychosis (IRR = 1.44; 95% CI, 1.39-1.49). The higher increased rate was noted separately for falls (IRR = 1.48; 95% CI, 1.43-1.54) and any fractures (IRR = 1.17; 95% CI, 1.08-1.27) as well as within specific types of fracture, including pelvis and hip fractures.ConclusionsOur findings suggest a modest but consistently higher increased risk of falls and fractures in PDP patients compared with PD patients without psychosis

Air Pollution Exposure during Pregnancy and Childhood Autistic Traits in Four European Population-Based Cohort Studies: The ESCAPE Project.

BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. OBJECTIVES: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. METHODS: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. RESULTS: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. CONCLUSIONS: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies.Funding was provided as follows: ESCAPE Project— European Community’s Seventh Framework Program (FP7/2007-2011-GA#211250). CATSS, Sweden— Swedish Research Council for Health, Working Life and Welfare (FORTE), Swedish Research Council (VR) Formas, in partner hip with FORTE and VINNOVA (cross-disciplinary research program concerning children’s and young people’s mental health); VR through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant 340-2013-5867; HKH Kronprinsessan Lovisas förening för barnasjukvård; and the Strategic Research Program in Epidemiology at Karolinska Institutet. Generation R, the Netherlands—The Generation R Study is conducted by the Erasmus University Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus University Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The Netherlands Organisation for Applied Scientific Research (TNO) received funding from the Netherlands Ministry of Infrastructure and the Environment to support exposure assessment. GASPII, Italy—grant from the Italian Ministry of Health (ex art.12, 2001). INMA, Spain— grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041 FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI041436, FIS-PI081151, FIS-PI06/0867, FIS-PS09/00090), PI13/1944, PI13_02032, PI14/0891, PI14/1687, MS13/00054, UE (FP7-ENV-2011 cod 282957, and HEALTH.2010.2.4.5-1); Generalitat de Catalunya-CIRIT 1999SGR 00241; La Fundació La Marató de TV3 (090430); Conselleria de Sanitat Generalitat Valenciana; Department of Health of the Basque Government (2005111093 and 2009111069); and Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). V.W.V.J. received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw 90700303, 916.10159). A.G.’s work was supported by a research grant from the European Community’s 7th Framework Programme (FP7/2008–2013-GA#212652). A full roster of the INMA project investigators can be found online (http://www. proyectoinma.org/presentacion-inma/listado-investigadores/ en_listado-investigadores.html)