Infant reference intervals - Steps towards improving the supportive data for result interpretation

Aim
To fully take advantage of blood test results, comparative data are required. Today, the reference interval is a commonly used concept. This review aims to summarise the current state of reference intervals, focusing on infants.

Methods
Literature on reference percentiles (birth to 12 months of age) published from January 1950 until November 2024 was reviewed. Search terms comprised paediatric, infant, or neonatal reference intervals and similar terminology. Furthermore, reference interval data in current clinical use were investigated by searching 7 Nordic laboratory websites for three routinely used biomarkers.

Results
During infancy, the levels of several biomarkers change rapidly with development and growth. Conventionally used techniques for deriving reference intervals have limitations and require extensive blood samplings. New approaches basing reference limits on mathematically trimmed data from laboratory systems have emerged. Due to the risk of modelling pathological data, the results of these studies need verification. Recently published Nordic reference interval data, based on healthy infants and defined on specified time points, could present new opportunities.

Conclusion
Infant reference interval methodology requires particular consideration. The currently observed heterogeneity in this area calls for further methodological investigations, improved concepts, harmonisation activities, and software development.