Designing a childrens health exposomics study protocol: The CHILDREN_FIRST multi-country prospective cohort using multi-omics and personalized prevention approache

1Non-communicable diseases (NCDs) account for [~]71% of all deaths globally, including 15 million premature deaths each year (deaths between 30-69 years of age). Instead of waiting until the disease manifestation, focusing on the origins of NCDs during childhood offers a critical window of disease prevention and control for effective interventions. The CHILDREN_FIRST study aims to investigate how the spatio-temporal evolution of the childrens exposome profiles in the Mediterranean region influences the early-life programming of chronic disease risk during the unique critical window of susceptibility in the primary school years (6-11 years of age). The study protocol adopts the human exposome framework integrated with a personalized prevention approach using multi-omics platforms and advanced machine learning algorithms implemented across five Mediterranean countries, namely Cyprus, Greece, Spain, Israel, and Albania. The cohort will consist of children enrolled in the first grade of primary school, who will undergo annual follow-up assessments until completion of primary education. During the annual assessments, childrens exposome parameters from the three main exposome domains will be evaluated using different assessment types i.e., biospecimen, sensors, questionnaires. Standardized human sample and data collection methods will be employed following harmonized standardized operating procedures. The reference model of Observational Medical Outcomes Partnership - Common Data Model part of the Observational Health Data Sciences and Informatics will be used to conduct federated data analysis. This CHILDREN_FIRST study protocol is a human exposome-based initiative to establish a long-term prospective cohort infrastructure for biomedical research on childrens health within the Mediterranean region. The cohorts exposome-based findings will systematically feed into the evaluation and design of chronic disease prevention programs. Expected results would inform evidence-based policy making and the development of health interventions for reducing the risk of NCDs.