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Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6–11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (−1.25; −2.10, −0.40), house crowding (−0.39; −0.62, −0.16), and child environmental tobacco smoke (ETS) (−0.89; −1.42, −0.35), were all associated with lower CPM scores. Indoor PM2.5 exposure was associated with lower N-Back scores (−0.09; −0.16, −0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely and cross-sectionally associate with cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality., Graphical abstract Prenatal and childhood exposome-wide associations with child fluid intelligence (CPM). The exposures selected by Deletion-substitution-addition algorithm are represented by a triangle. Child fluid intelligence is mainly associated with childhood exposome, fast-food (negative association, left sided) and organic food consumption (positive, right sided), house crowding (negative, left sided), and child environmental tobacco smoke (ETS, negative, left sided). Image 1, Highlights • Previous evidence for environmental risk factor associations with neurodevelopment is based on analyses of single exposures. • We systematically analysed multiple environmental exposures in relation to child neurodevelopment. • The findings describe a list of outcome-related exposures: Diet, house crowding, indoor air pollution and tobacco smoke. • The findings show methodological complexities of analysing multiple exposures and their associations with neurodevelopment.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho

Introduction: Early onset and high prevalence of allergic diseases result in high individual and socio-economic burdens. Several studies provide evidence for possible effects of environmental factors on allergic diseases, but these are mainly single-exposure studies. The exposome provides a novel holistic approach by simultaneously studying a large set of exposures. The aim of the study was to evaluate the association between a broad range of prenatal and childhood environmental exposures and allergy-related outcomes in children. Material and methods: Analyses of associations between 90 prenatal and 107 childhood exposures and allergy-related outcomes (last 12 months: rhinitis and itchy rash; ever: doctor-diagnosed eczema and food allergy) in 6-11 years old children (n = 1270) from the European Human Early-Life Exposome cohort were performed. Initially, we used an exposome-wide association study (ExWAS) considering the exposures independently, followed by a deletion-substitution-addition selection (DSA) algorithm considering all exposures simultaneously. All the exposure variables selected in the DSA were included in a final multi-exposure model using binomial general linear model (GLM). Results: In ExWAS, no exposures were associated with the outcomes after correction for multiple comparison. In multi-exposure models for prenatal exposures, lower distance of residence to nearest road and higher di-iso-nonyl phthalate level were associated with increased risk of rhinitis, and particulate matter absorbance (PMabs) was associated with a decreased risk. Furthermore, traffic density on nearest road was associated with increased risk of itchy rash and diethyl phthalate with a reduced risk. DSA selected no associations of childhood exposures, or between prenatal exposures and eczema or food allergy. Discussion: This first comprehensive and systematic analysis of many environmental exposures suggests that prenatal exposure to traffic-related variables, PMabs and phthalates are associated with rhinitis and itchy rash. This work was supported by the European Community’s Seventh Framework Programme [grant agreement no 308333—the HELIX project]; Instituto de Salud Carlos III; CIBERESP; Conselleria de Sanitat; Generalitat Valenciana; Department of Health of the Basque Government; Provincial Government of Gipuzkoa; Generalitat de Catalunya-CIRIT; Lithuanian Agency for Science Innovation and Technology [grant number 6-04-2014_31V-66]; Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; Greek Ministry of Health; Ministerio de Ciencia Innovacion y Universidades [grant number MTM2015-68140-R]; Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII; Fondation de France.

Background: Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. Objectives: Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. Methods: The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. Results: The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. Discussion: This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975. This study received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 308333 – the HELIX project for data collection and analyses. The HELIX program built on six existing cohorts that received previous funding, including the major ones listed below. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, National Institutes of Health (NIH)/ National Institute of Environmental Health Sciences (NIEHS) (contract no. N01-ES-75558), and NIH/NINDS (grants 1 UO1 NS 047537-01 and 2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus,” Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). M.C. received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). L.C. was supported by the NIH/NIEHS grants R21ES029681, R01ES030691, R01ES029944, R01 ES030364, R21ES028903, and P30ES007048.

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities. This work was supported by the European Commission Seventh Framework Programme (FP7/2007–2013) [grant number: 308333–the HELIX project]. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7-HEALTH-2012 Proposal No 308333 HELIX, FP7 European Union project, No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15).

FI=3.835 (año 2016), Q1 Background: Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed. Objectives: To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case-control study of childhood renal cancer in Spain, including 213 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 1278 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries, the 30 urban areas with ≥75,000 inhabitants, and the agricultural crops located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. Results: Excess risk (OR; 95%CI) of childhood renal tumors was observed for children living near (≤2.5km) industrial installations as a whole (1.97; 1.13-3.42) - particularly glass and mineral fibers (2.69; 1.19-6.08), galvanization (2.66; 1.14-6.22), hazardous waste (2.59; 1.25-5.37), ceramic (2.35; 1.06-5.21), surface treatment of metals (2.25; 1.24-4.08), organic chemical industry (2.22; 1.15-4.26), food and beverage sector (2.19; 1.18-4.07), urban and waste-water treatment plants (2.14; 1.07-4.30), and production and processing of metals (1.98; 1.03-3.82) -, and in the proximity of agricultural crops (3.16; 1.54-8.89 for children with percentage of crop surface ≥24.35% in a 1-km buffer around their residences). Conclusions: Our study provides some epidemiological evidence that living near certain industrial areas and agricultural crops may be a risk factor for childhood renal cancer. This study was funded by Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416 and FIS CP11/00112). No

BACKGROUND: Environmental exposures are related to the risk of some types of cancer, and children are the most vulnerable group of people. This study seeks to present the methodological approaches used in the papers of our group about risk of childhood cancers in the vicinity of pollution sources (industrial and urban sites). A population-based case-control study of incident childhood cancers in Spain and their relationship with residential proximity to industrial and urban areas was designed. Two methodological approaches using mixed multiple unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) were developed: (a) "near vs. far" analysis, where possible excess risks of cancers in children living near ("near") versus those living far ("far") from industrial and urban areas were assessed; and (b) "risk gradient" analysis, where the risk gradient in the vicinity of industries was assessed. For each one of the two approaches, three strategies of analysis were implemented: "joint", "stratified", and "individualized" analysis. Incident cases were obtained from the Spanish Registry of Childhood Cancer (between 1996 and 2011). RESULTS: Applying this methodology, associations between proximity (≤ 2 km) to specific industrial and urban zones and risk (OR; 95% CI) of leukemias (1.31; 1.04-1.65 for industrial areas, and 1.28; 1.00-1.53 for urban areas), neuroblastoma (2.12; 1.18-3.83 for both industrial and urban areas), and renal (2.02; 1.16-3.52 for industrial areas) and bone (4.02; 1.73-9.34 for urban areas) tumors have been suggested. CONCLUSIONS: The two methodological approaches were used as a very useful and flexible tool to analyze the excess risk of childhood cancers in the vicinity of industrial and urban areas, which can be extrapolated and generalized to other cancers and chronic diseases, and adapted to other types of pollution sources. This study was funded by Carlos III Institute of Health, Spain Grand EPY1344/16, Spain’s Health Research Fund (Fondo de Investigación Sanitaria—FIS 12/01416), and Scientific Foundation of the Spanish Association Against Cancer, Spain (Fundación Científica de la Asociación Española Contra el Cáncer (AECC)—EVP-1178/14). This article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health. Sí

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. Objective: We evaluated the association of the urban exposome with birth weight. Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures. Results: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis. Conclusion: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement No. 308333—the HELIX project—for data collection and analyses. The HELIX program built on six existing cohorts that received previous funding, including the major cohorts listed here. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, the Conselleria de Sanitat, Generalitat Valenciana, Department of Health of the Basque Government; the Provincial Government of Gipuzkoa, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). MoBa (Norwegian Mother and Child Cohort Study) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (Contract No. N01-ES-75558), and the U.S. National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS; Contract No. N01-ES-75558), and National Institute of Neurological Disorders and Stroke (Grant No. 1 UO1 NS 047537-01 and Grant No. 2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects (EU FP6–2003-Food-3-NewGeneris, EU FP6.STREP Hiwate, EU FP7 ENV.2007·1.2.2.2, Project No. 211250 Escape, EU FP7–2008-ENV-1·2.1·4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6, Proposal No. 226285 ENRIECO, EUFP7-HEALTH-2012 Proposal No. 308333 HELIX, FP7 European Union Project No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). L.C. received additional funding from the Southern California Environmental Health Sciences Center (Grant No. P30ES007048) funded by NIEHS. We acknowledge the support of the program for international scientific collaborations of Région Rhône-Alpes-Auvergne.

Background: Several environmental contaminants were reported to possibly influence fetal growth, generally from single exposure family studies, which are prone to publication bias. The exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. Objectives: We aimed to assess the association of the pregnancy chemical and external exposomes with fetal growth. Methods: Within HELIX project, 131 prenatal exposures were assessed using biomarkers and environmental models in 1,287 mother-child pairs from six European cohorts. We investigated their associations with fetal growth using a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering each exposure independently. We corrected for exposure misclassification, and tested for exposure-exposure and sex-exposure interactions. Findings: Lead blood level was the only exposure associated with fetal growth in the DSA model (97g weight decrease for each doubling in lead concentration). No exposure passed the multiple testing-corrected significance threshold of ExWAS; without multiple testing correction, this model was in favor of a negative association of fine particulate matter concentration with birth weight; and of a positive sex-specific association of parabens with birth weight in boys only. No two-way interaction between exposure variables was identified. Interpretation: This first large-scale exposome study of fetal growth simultaneously considered over 100 environmental exposures. Compared to single exposure studies, our approach allowed making all tests (usually reported in successive publications) explicit. Lead exposure is still a health concern in Europe and parabens health effects warrant further investigation. Funding Statement: FP7/2007-2013, HELIX project (no 308333). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the relevant ethical committees from each country and an informed consent form was assigned from all participants, or the parents of the children.

BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women. METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts - Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2:5 μm, ≤10 μm, and 2:5–10 μm in diameter (PM2:5, PM10, and PMcoarse, respectively); PM2:5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2:5 {hazard ratio (HR) =1:08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m3 }, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m3 ], PMcoarse [1.20 (95% CI: 0.96, 1.49 per 5 μg/m3 ], and NO2 [1.02 (95% CI: 0.98, 1.07 per 10 μg/m3 ], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m3, p =0:04]. CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women. © 2017, Public Health Services, US Dept of Health and Human Services. All rights reserved. Chemicals/CAS: copper, 15158-11-9, 7440-50-8; iron, 14093-02-8, 53858-86-9, 7439-89-6; nickel, 7440-02-0; nitrogen oxide, 11104-93-1; potassium, 7440-09-7; silicon, 7440-21-3; sulfur, 13981-57-2, 7704-34-9; vanadium, 7440-62-2; zinc, 7440-66-6, 14378-32-6

Urban rat infestations have multifactorial causes and may result in severe public health and environmental problems, as well as heavy economic losses. The identification of putative environmental determinants of urban rat infestations and the mapping of areas prone to experiencing such infestations (hot spots) are crucial for effectively addressing intervention efforts. We investigated the associations between a selection of environmental factors and the occurrence of rat infestations in the city of Madrid, Spain. This was done by modelling 10,956 citizen-reported rat sightings from 2002 to 2008 using generalized additive models, both at municipality (Madrid) and district (Latina) levels. Increased age and density of housing, and decreased distance to vegetated areas, markets and cat feeding stations were factors associated with an increased risk of rat infestations. Risk maps for rat infestations were also developed and recurrent hot spots of rat activity were identified. Although a better fit to the data was obtained in the model for the smaller scale and possibly more environmentally homogenous study area of Latina, modelling the spatial distribution of rat sightings was useful for identifying factors associated with an increased risk of urban rat infestations, as well as for identifying hot spots of rat activity, providing local authorities with a practical tool for effectively targeting intervention efforts to high-risk situations based on the local environmental contexts.

Few epidemiologic studies have explored risk factors for bone tumors in children, and the role of environmental factors needs to be analyzed. Our objective was to ascertain the association between residential proximity to industrial plants and urban areas and risk of bone tumors in children, taking into account industrial groups and toxic pollutants released. A population-based case-control study of childhood bone cancer in Spain was carried out, covering 114 incident cases obtained from the Spanish Registry of Childhood Tumors (between 1996 and 2011), and 684 controls individually matched by sex, year of birth, and autonomous region of residence. Distances from the subject's residences to the 1271 industries and the 30 urban areas (towns) with ≥75,000 inhabitants located in the study area were computed. Unconditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1km to 3km) to industrial and urban areas, with adjustment for matching variables and sociodemographic indicators. Excess risk (OR; 95%CI) of bone tumors in children was detected for children close to industrial facilities as a whole (2.33; 1.17-4.63 at 3km) - particularly surface treatment of metals (OR=2.50; 95%CI=1.13-5.56 at 2km), production and processing of metals (OR=3.30; 95%CI=1.41-7.77 at 2.5km), urban waste-water treatment plants (OR=4.41; 95%CI=1.62-11.98 at 2km), hazardous waste (OR=4.63; 95%CI=1.37-15.61 at 2km), disposal or recycling of animal waste (OR=4.73; 95%CI=1.40-15.97 at 2km), cement and lime (OR=3.89; 95%CI=1.19-12.77 at 2.5km), and combustion installations (OR=3.85; 95%CI=1.39-10.66 at 3km)-, and urban areas (4.43; 1.80-10.92). These findings support the need for more detailed exposure assessment of certain toxics released by these facilities. Fondo de Investigación Sanitaria y Asociación Española Contra el Cáncer (AECC) Sí

Background: We define the 'Outdoor Exposome' as the complex mixture of environmental factors that individuals are exposed to in the outdoor environment, which may be determined by socio-demographic...

Background: Few epidemiologic studies have explored risk factors for rare tumors in children, and the role of environmental factors needs to be assessed. Objectives: To ascertain the effect of residential proximity to both industrial and urban areas on childhood cancer risk, taking industrial groups into account. Methods: We conducted a population-based case-control study of five childhood cancers in Spain (retinoblastoma, hepatic tumors, soft tissue sarcomas, germ cell tumors, and other epithelial neoplasms/melanomas), including 557 incident cases from the Spanish Registry of Childhood Tumors (period 1996-2011), and 3342 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. Results: Children living near industrial and urban areas as a whole showed no excess risk for any of the tumors analyzed. However, isolated statistical associations (OR; 95%CI) were found between retinoblastoma and proximity to industries involved in glass and mineral fibers (2.49; 1.01-6.12 at 3km) and organic chemical industries (2.54; 1.10-5.90 at 2km). Moreover, soft tissue sarcomas registered the lower risks in the environs of industries as a whole (0.59; 0.38-0.93 at 4km). Conclusions: We have found isolated statistical associations between retinoblastoma and proximity to industries involved in glass and mineral fibers and organic chemical industries. This study was funded by Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416) and Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14). No

Background: Neuroblastoma is the most common extracranial solid tumor in children but its etiology is not clearly understood. While a small fraction of cases might be attributable to genetic factors, the role of environmental pollution factors needs to be assessed. Objectives: To ascertain the effect of residential proximity to both industrial and urban areas on neuroblastoma risk, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case-control study of neuroblastoma in Spain, including 398 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996–2011), and 2388 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 5 km) to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. Results: Excess risk (OR; 95%CI) of neuroblastoma was detected for the intersection between industrial and urban areas: (2.52; 1.20–5.30) for industrial distance of 1 km, and (1.99; 1.17–3.37) for industrial distance of 2 km. By industrial groups, excess risks were observed near ‘Production of metals’ (OR = 2.05; 95%CI = 1.16–3.64 at 1.5 km), ‘Surface treatment of metals’ (OR = 1.89; 95%CI = 1.10–3.28 at 1 km), ‘Mines’ (OR = 5.82; 95%CI = 1.04–32.43 at 1.5 km), ‘Explosives/pyrotechnics’ (OR = 4.04; 95%CI = 1.31–12.42 at 4 km), and ‘Urban waste-water treatment plants’ (OR = 2.14; 95%CI = 1.08–4.27 at 1.5 km). Conclusions: These findings support the need for more detailed exposure assessment of certain substances released by these industries. Keywords: Neuroblastoma, Industrial pollution, Urban pollution, Case-control study, Residential proximity, Pollutant release and transfer register

This study aimed to describe the degree of annoyance among pregnant women in a Spanish cohort and to examine associations with proximity to traffic, NO2 and benzene exposure. We included 2457 participants from the Spanish Childhood and Environment study. Individual exposures to outdoor NO2 and benzene were estimated, temporally adjusted for pregnancy. Interviews about sociodemographic variables, noise and air pollution were carried out. Levels of annoyance were assessed using a scale from 0 (none) to 10 (strong and unbearable), a level of 8 to 10 was considered high. The reported prevalence of high annoyance levels from air pollution was 11.2% and 15.0% from noise, the two variables were moderately correlated (0.606). Significant correlations between NO2 and annoyance from air pollution (0.154) and that from noise (0.181) were observed. Annoyance owing to noise and air pollution had a low prevalence in our Spanish population compared with other European populations. Both factors were associated with proximity to traffic. In multivariate models, annoyance from air pollution was related to NO2, building age, and country of birth, annoyance from noise was only related to the first two. The health burden of these exposures can be increased by stress caused by the perception of pollution sources.

Background Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer. The difficulty of collecting personal environmental exposure data is an important limitation; this lack of information about pesticides motivates the development of new methods to subrogate this exposure. We developed a crop exposure index based on geographic information to study the relationship between exposure to different types of crops and risk of childhood tumors. Methods We conducted a population-based case–control study of childhood cancer covering 3350 cases and 20,365 controls in two Spanish regions. We used CORINE Land Cover to obtain data about agricultural land use. We created a 1 km buffer around every child and calculated the percentage of crop surface within the buffer (Global Crop Index) for total crops and for individual types of crops. We fitted mixed multiple unconditional logistic regression models by diagnostic group. Results We found excess of risk among children living in the proximity of crops. For total crops our results showed excesses of risk for almost all diagnostic groups and increasing risk with increasing crop index value. Analyses by region and individual type of crop also showed excess of risk. Conclusion The results suggest that living in the proximity of cultivated land could be a risk factor for several types of cancer in children. This study was funded by Spain’s Health Research Fund (Fondo de Investigación Sanitaria—FIS 12/01416) and Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC)—EVP-1178/14). Sí

Graphical abstract, Highlights • A wide range of pre- and postnatal environmental exposures affects child behavior. • The exposome includes outdoor, indoor, chemical, lifestyle and social exposures. • Maternal tobacco smoke and car traffic increased behavioural problems in children. • Child sleep, healthy diet and higher family social capital reduced symptoms. • Child exposure to lead, copper, indoor air pollution, increased symptoms., Background Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior. Methods and findings We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6–11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner’s Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent’s reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides. Conclusions Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk.