Reference intervals for holotranscobalamin and total vitamin B12 in 6-12-year-old children in Norway: the Health Oriented Pedagogical Project (HOPP)

Vitamin B12 (B12) is essential for DNA synthesis in all cells and for the development and maintenance of a healthy nervous system. B12 is transported in the circulation bound to two carrier proteins, haptocorrin and transcobalamin, measured as the biomarkers total B12 and holotranscobalamin (holoTC). The latter measures the fraction of cobalamin available for tissue uptake and is considered to have a better sensitivity and specificity for diagnosing vitamin deficiency. The concentration of both carrier proteins depends on age, but data on paediatric reference values for holoTC are still sparse. Blood samples were obtained from 1320 healthy school children, mainly Caucasians (age 6-12 years old) in three different municipalities in Norway. The holoTC and total B12 levels were determined by chemiluminescent microparticle immunoassay on the Architect 2000 analyser. Age specific paediatric reference intervals (RIs) were estimated by calculating the 2.5 and 97.5 percentiles by the nonparametric method with corresponding 90% confidence intervals, according to the Clinical and Laboratory Standards Institute C28-A3C guidelines. The 95% RIs for total B12 were 295-1066 pmol/L for children 6-8 years old, and 249-879 pmol/L for children 9-12 years old. Reference intervals for holoTC were >= 56 pmol/L for children 6-8 years old, and >= 37 pmol/L for children 9-12 years old. Age specific RIs will aid clinicians in interpretation of cobalamin results in children aged 6-12 years old.