Impact of the Social and Natural Environment on Preschool-Age Children Weight

Background: The complex impact of environmental and social factors on preschool children being overweight/obese is unclear. We examined the associations between the levels of green space exposure and the risk of being overweight/obese for 4-6 year-old children and assessed the impact of maternal education on these associations. Methods: This cross-sectional study included 1489 mother-child pairs living in Kaunas, Lithuania, in 2012-2013. We assessed children overweight/obesity by standardized questionnaires using international body mass index cut-off points, and the level of greenness exposures by satellite-derived normalized difference vegetation index (NDVI) of each child's home and by the distance to a nearest city park. The maternal education was used as the SES indicator. We used logistic regression models to investigate the strength of the associations. Results: Children from families with poorer maternal education, pathological mother-child relations and smoking mothers, and living in areas with less greenness exposure (NDVI-100 m), had significantly higher odds ratios of being overweight/obese. Lower maternal education and distance to a city park modified the effect of greenness cover level exposure on the risk of children being overweight/obese. Conclusions: Higher greenness exposure in the residential settings has beneficial effects on children's physical development. The green spaces exposures for psychosocial stress management is recommended as a measure to prevent overweight/obesity among children

Determinants of the urinary and serum metabolome in children from six European populations

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children

Impact of Psychosocial Environment on Young Children’s Emotional and Behavioral Difficulties

Objective: The impact of maternal psychosocial stress on young children’s mental difficulties is unclear. This study investigated the joint effects of the socioeconomic status and parent-child relationships on emotional and behavioral difficulties in preschool children. Methods: The case-control study included 1416 mothers and their 4–6 year-old children pairs, living in Kaunas city, Lithuania. The parent-child relationships were measured using the Parent-Child Dysfunctional Interaction subscale. Children’s mental health difficulties were assessed by the Strengths and Difficulties Questionnaire. We used logistic regression models to indicate the strength of the associations. Results: Lower socioeconomic status women more often than higher ones reported pathological mother-child relations. Low education level was associated with statistically significant increase adjusted odds ratios for emotional symptoms and total behavioral difficulties. With reference to the group of better-educated mothers and normal mother-child relations, low education and pathological mother-child relations statistically significantly increased the risk of total difficulties in 4–6 year-old children; the adjusted odds ratios were 2.45; 95% CI 1.51–3.99. Conclusions: Pathological mother-child relations strengthened the effect of lower education on the increased risk of emotional and behavioral difficulties in preschool-age children. Measures oriented towards health behavior and psychosocial difficulties management may decrease children’s emotional and behavioral difficulties

Impact of the Social and Natural Environment on Preschool-Age Children Weight

Background: The complex impact of environmental and social factors on preschool children being overweight/obese is unclear. We examined the associations between the levels of green space exposure and the risk of being overweight/obese for 4-6 year-old children and assessed the impact of maternal education on these associations. Methods: This cross-sectional study included 1489 mother-child pairs living in Kaunas, Lithuania, in 2012-2013. We assessed children overweight/obesity by standardized questionnaires using international body mass index cut-off points, and the level of greenness exposures by satellite-derived normalized difference vegetation index (NDVI) of each child's home and by the distance to a nearest city park. The maternal education was used as the SES indicator. We used logistic regression models to investigate the strength of the associations. Results: Children from families with poorer maternal education, pathological mother-child relations and smoking mothers, and living in areas with less greenness exposure (NDVI-100 m), had significantly higher odds ratios of being overweight/obese. Lower maternal education and distance to a city park modified the effect of greenness cover level exposure on the risk of children being overweight/obese. Conclusions: Higher greenness exposure in the residential settings has beneficial effects on children's physical development. The green spaces exposures for psychosocial stress management is recommended as a measure to prevent overweight/obesity among children

Variability of urinary concentrations of non-persistent chemicals in pregnant women and school-aged children

Background: Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions. Objectives: We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children. Methods: 154 pregnant women and 152 children from six European countries were enrolled in 2014–2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80. Results: All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40–0.59) to good (0.60–0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15–20 urines each would be necessary to obtain an ICC above 0.80. Conclusions: This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months.The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 308333 – the HELIX project. Dr. Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). Dr. Regina Grazuleviciene received the grant of the Lithuanian Agency for Science Innovation and Technology (No. 31V-66). Dr. Juan R Gonzalez is supported by Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo (MTM2015-68140-R). The pregnant women recruited in Grenoble are part of SEPAGES mother-child cohort, which has been partly funded by a grant from the European Research Council (ERC, consolidator grant #311765-EDOHaD, PI, R. Slama)

The early-life exposome: Description and patterns in six European countries

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)

Human Early Life Exposome (HELIX) study: a European population-based exposome cohort

PURPOSE: Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. PARTICIPANTS: The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). FINDINGS TO DATE: Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. FUTURE PLANS: HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333—the HELIX project. Dr Maribel Casas and Dr Jordi Julvez received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128, MS14/00108). 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). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), and 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, 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). The work was also supported by MICINN (MTM2015-68140-R) and Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII. CW received funding from the Fondation de France