Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic profiles: A panel study.

BACKGROUND: Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs. METHODS: We used data from the HELIX Child Panel Study, which included 156 children aged 6 to 11. Children were followed for one week, in two time periods. Twenty-two non-persistent EDCs (10 phthalate, 7 phenol, and 5 organophosphate pesticide metabolites) were measured in two weekly pools of 15 urine samples each. Multi-omic profiles (methylome, serum and urinary metabolome, proteome) were measured in blood and in a pool urine samples. We developed visit-specific Gaussian Graphical Models based on pairwise partial correlations. The visit-specific networks were then merged to identify reproducible associations. Independent biological evidence was systematically sought to confirm some of these associations and assess their potential health implications. RESULTS: 950 reproducible associations were found among which 23 were direct associations between EDCs and omics. For 9 of them, we were able to find corroborating evidence from previous literature: DEP - serotonin, OXBE - cg27466129, OXBE - dimethylamine, triclosan - leptin, triclosan - serotonin, MBzP - Neu5AC, MEHP - cg20080548, oh-MiNP - kynurenine, oxo-MiNP - 5-oxoproline. We used these associations to explore possible mechanisms between EDCs and health outcomes, and found links to health outcomes for 3 analytes: serotonin and kynurenine in relation to neuro-behavioural development, and leptin in relation to obesity and insulin resistance. CONCLUSIONS: This multi-omics network analysis at two time points identified biologically relevant molecular signatures related to non-persistent EDC exposure in childhood, suggesting pathways related to neurological and metabolic outcomes.

Evaluation of a child food reward task and its association with maternal feeding practices.

Food reward is defined as the momentary value of a food to the individual at the time of ingestion and is characterised by two psychological processes-"liking" and "wanting". We aimed to validate an age-appropriate food reward task to quantify implicit wanting of children from the GUSTO cohort (n = 430). At age 5 years, child appetitive traits and maternal feeding practices were reported by mothers via questionnaires. At age 6, a write-for-food task based on the child's preference for food or toy rewards was undertaken in laboratory conditions. Child BMI and skinfold measurements were taken at age 7. Convergent validity of the food reward task was assessed by associating with child appetitive traits, where enjoyment of food/food responsiveness (OR: 1.51; 95% CI: 1.06, 2.15) and emotional overeating (OR: 1.64; 95% CI: 1.09, 2.48) were positively associated with high food reward in children. Criterion validity was tested by associating with child BMI, however no significant relationships were observed. Multivariable logistic regression analysis with maternal feeding practices revealed that children whose mother tend to restrict unhealthy food (OR: 1.37; 95% CI: 1.03, 1.82) and girls whose mothers taught them about nutrition (OR: 2.09; 95% CI: 1.19, 3.67) were more likely to have high food reward. No further significant associations were observed between food reward, other appetitive traits and feeding practices. Despite the lack of association with child weight status, this study demonstrated the value of the write-for-food task to assess food reward in children and presented sex-specific associations with maternal feeding practices.