AUTHOR=Maccarini Beatrice , Loperfido Federica , Bianco Irene , Sottotetti Francesca , El Masri Dana , Ferrara Chiara , Verme Federica , Cangelosi Erika , Meriggi Niccolò , De Filippo Carlotta , Cena Hellas , De Giuseppe Rachele TITLE=Offspring's exposome: a narrative review on the influence of early-life factors on childhood obesity risk JOURNAL=Frontiers in Nutrition VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1597746 DOI=10.3389/fnut.2025.1597746 ISSN=2296-861X ABSTRACT=Childhood obesity has emerged as a global health challenge, with significant long-term health consequences, including an increased risk of non-communicable diseases. The “first 1,000 days” period of life is a critical window for shaping long-term health outcomes. This narrative review aims to explore the role of environmental exposures, categorized within the exposome framework, in developing childhood obesity. The exposome encompasses three domains: general external exposures (e.g., air pollution, urbanization), specific external exposures [e.g., nutrition, physical activity, socioeconomic status (SES)], and internal exposures (e.g., metabolic responses, oxidative stress). Evidence identifies risk factors such as maternal smoking during pregnancy, early-life exposure to endocrine-disrupting chemicals, and air pollution, which contribute to obesogenic processes. In contrast, protective factors include access to green and blue spaces, exclusive breastfeeding, adequate complementary feeding, regular physical activity, limited screen time, and sufficient sleep, which support healthy growth trajectories. Findings regarding SES, perfluoroalkyl and polyfluoroalkyl substances exposure, and human breast milk macronutrient composition remain heterogeneous and context-dependent. The findings highlight the need to integrate public health strategies addressing modifiable environmental and lifestyle factors. Identifying a “healthy exposome” that protects against obesity risk can steer the development of personalized prevention strategies, ultimately reducing the burden of obesity and associated diseases.