From genes to environment: A life-course approach to prevent pediatric autoimmune diseases

Autoimmune diseases in children, including type 1 diabetes, celiac disease, and juvenile arthritis, represent a growing global health challenge. This surge, too rapid to be explained by genetic shifts alone, highlights the critical role of environmental factors and underscores the urgent need for proactive prevention. This review presents an integrated, evidence-based framework for preventing pediatric autoimmune diseases across the care spectrum, from primordial to tertiary prevention. We define high-risk pediatric populations using a multidimensional approach that integrates family history, genetic data (e.g. , polygenic risk scores), and preclinical biomarkers. The review details a multi-tiered prevention strategy: Primordial prevention focuses on optimizing maternal and early-life health to establish immune tolerance in the first 1000 days; primary prevention targets at-risk children with personalized nutritional and lifestyle interventions; secondary prevention uses early screening and surveillance to identify preclinical autoimmunity, allowing for targeted immunomodulatory therapies that can delay or prevent disease onset; and tertiary prevention employs early aggressive therapy to limit long-term complications in children with established disease. By synthesizing epidemiological data, mechanistic understanding, and a comprehensive prevention framework, this article aims to inform clinical practice, guide research priorities, and support public health policies to combat the increasing incidence of pediatric autoimmunity.