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 ). 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). 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. 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.

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.

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.