Small patients, big challenges: navigating the complex world of pediatric reference intervals

With about 60%-70% of medical decisions based on laboratory investigations, modern medicine is increasingly more reliant on laboratory medicine. Pediatric healthcare particularly depends on laboratory testing, with reference intervals (RIs) serving as critical tools for accurate result interpretation. However, establishing pediatric RIs poses distinctive challenges due to developmental, growth, nutritional, and disease-related variations across age groups, along with technical, ethical, and logistical challenges. Despite these limitations, there are several ongoing initiatives for developing pediatric RIs globally, underscoring the importance of developing accurate pediatric RIs. This review outlines the particularities of pediatric laboratory medicine and the specific challenges in establishing pediatric RIs, highlighting the recent initiatives in this area. It also addresses biological and analytical variability issues and explores future perspectives aimed at enhancing diagnostic accuracy and elevating patient care standards.