Abstract
Background: The exposome encompasses the totality of environmental exposures from conception onwards. The Human Early Life Exposome (HELIX) project offers a unique opportunity to explore the interplay between the early-life exposome and the molecular responses in childhood.Method: HELIX consists of 1,300 children aged 6-11 years from 6 European cohorts (BIB in UK, EDEN in France, KANC in Lithuania, INMA in Spain, MOBA in Norway, and RHEA in Greece). The child’s prenatal and early life exposome included >200 variables: air pollution, build environment, noise, cotinine, metals, POPs, PFAS, phthalates, phenols, and organophosphates, and life-style factors (socio-economic capital, diet and physical activity). Cross-sectional molecular measurements were obtained, including blood DNA methylation, gene and miRNA transcription, serum and urinary metabolites and plasma proteins. The exposome was related to the molecular marks through linear regression models.Results: During the prenatal period, exposure to tobacco (maternal active smoking, urinary cotinine and cadmium) was associated with DNA methylation at age 6-11 years. Moreover, maternal levels of essential metals and elements (i.e. zinc) were also associated with DNA methylation. During the postnatal period, child PFAS, mercury, arsenic and selenium were associated with metabolites derived from fish intake (i.e. polyunsaturated fatty acids (PUFA)); and child organophosphate pesticides were associated with urine metabolites related to fruit consumption (i.e. proline betaine). Further associations were found with copper and persistent pollutants across several omics suggesting a link to systemic inflammation and adiposity.Conclusion: While main associations of the prenatal exposome were with childhood DNA methylation, cross-sectional exposures were more related to metabolic profiles and proteins. Molecular biomarkers informed about source of exposure (i.e. fish) and about molecular mechanisms (i.e. inflammation).
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