Proteomic Data Underscore Need for Age-Specific Pediatric Reference Ranges

Yet pediatric interpretation often relies on adult reference intervals, which may not reflect developmental biology. Establishing age- and sex-specific norms is therefore a practical need for clinical laboratories. New findings highlight this gap by demonstrating pronounced, longitudinal shifts in circulating proteins from early childhood through young adulthood.

Karolinska Institutet (Stockholm, Sweden), in collaboration with SciLifeLab and KTH Royal Institute of Technology, conducted longitudinal protein profiling to characterize age- and sex-related trajectories in the circulating proteome. Investigators analyzed serial blood samples using advanced protein technology to quantify thousands of proteins and assess temporal patterns. The study indicates that adult reference values are inadequate for interpreting protein levels in children and adolescents.

The analysis included 100 participants from the population-based BAMSE cohort with blood samples collected at ages 4, 8, 16, and 24 years. More than 5,000 proteins were measured, of which just over 3,500 could be tracked over time. More than half of these proteins changed with age during childhood, with the greatest shifts between 8 and 16 years, a period coinciding with puberty; many proteins rose sharply during this interval and declined in early adulthood, while others changed more gradually.

Clear sex differences also emerged. In early childhood the differences were few, but they increased markedly from adolescence onward. By age 24, around 30% of proteins differed between women and men, including proteins linked to growth, metabolism, the immune system, and reproductive processes. Given that blood proteins are widely used as biomarkers, the authors note that differing levels in children may represent normal development rather than disease. They also acknowledge the limited sample size and that findings primarily apply to a relatively homogeneous population.

The work, published in Nature Communications, is part of the Human Disease Blood Atlas within the Human Protein Atlas and is based on the Swedish BAMSE cohort. Together, these resources provide a framework for mapping proteomic development across key life stages.

“Our study shows that reference values from adults cannot be used when interpreting protein levels in children and adolescents. Protein levels are strongly age-dependent even early in life,” said Sophia Björkander, assistant professor and docent at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.

“By mapping protein development, we are creating a reference that can be used to identify early deviations. This opens up possibilities for risk assessment of chronic diseases and more personalized medicine,” said Erik Melén, project leader at BAMSE and professor at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.

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