Reference intervals for iron-related blood parameters: results from a population-based cohort study (LIFE Child)

Abstract

Background: Pediatric reference intervals for iron-related parameters are determined continuously over time from a highly standardized sample collection by application of the R-package generalized additive models for location, scale and shape (GAMLSS), which is little known in laboratory medicine. Methods: Two thousand seven hundred and seventy-eight samples from Leipzig research center for civilization diseases (LIFE) Child participants at the age of 2.5–19 years were analyzed on a Sysmex XN-9000 for hemoglobin and reticulocytes and on a Roche Cobas 8000 for transferrin and ferritin. Reference intervals were established by repeated model calculation by use of the LMS (λ-µ-σ) method from Cole with specifically weighted subsamples. Results: Continuous and gender-specific reference intervals as well as smoothed percentile curves were established for hemoglobin, ferritin, reticulocytes and transferrin. In the case of repeated model calculations, single curves and averaged percentile curves were shown. The single curves outlined potential variations of the different parameter trends. The averaged percentile curves submitted a stable assessment of curve trends over time for iron-related parameters in childhood and adolescence. Conclusions: For the first time current age- and gender- specific reference intervals are available by application of the R-package GAMLSS and the laboratory techniques applied here. Compared to earlier studies, previous findings can be completed and discrepancies related to different methodical approaches, can be pointed out. Relevant findings for the diagnosis of iron deficiency anemia, such as gender-dependent assessment of hemoglobin starting at the age of 11 instead of 15 [according to the World Health Organization (WHO)], are presented.