The aim of HELIX is to exploit novel tools and methods (remote sensing/GIS-based spatial methods, omics-based approaches, biomarkers of exposure, exposure devices and models, statistical tools for combined exposures, novel study designs, and burden of disease methodologies), to characterise early-life exposure to a wide range of environmental hazards, and integrate and link these with data on major child health outcomes (growth and obesity, neurodevelopment, immune system), thus developing an “Early-Life Exposome” approach.HELIX uses six existing, prospective birth cohort studies as the only realistic and feasible way to obtain the comprehensive, longitudinal, human data needed to build this early-life exposome. These cohorts have already collected large amounts of data as part of national and EU-funded projects. Results will be integrated with data from European cohorts (>300,000 subjects) and registers, to estimate health impacts at the large European scale.HELIX will make a major contribution to the integrated exposure concept by developing an exposome toolkit and database that will: 1) measure a wide range of major chemical and physical environmental hazards in food, consumer products, water, air, noise, and the built environment, in pre and postnatal periods; 2) integrate data on individual, temporal, and toxicokinetic variability, and on multiple exposures, which will greatly reduce uncertainty in exposure estimates; 3) determine molecular profiles and biological pathways associated with multiple exposures using omics tools; 4) provide exposure-response estimates and thresholds for multiple exposures and child health; and 5) estimate the burden of childhood disease in Europe due to multiple environmental exposures. This integration of the chemical, physical and molecular environment during critical early-life periods will lead to major improvements in health risk and impact assessments and thus to improved prevention strategies for vulnerable populations.