Regression-based Reference Limits for Serum Transferrin Receptor in Children 6 Months to 16 Years of Age

Abstract

Serum soluble transferrin receptor (sTfR) has been established in recent years as a powerful tool for detecting iron deficiency (ID) in adults, especially in distinguishing between iron deficiency anemia (IDA) and anemia of chronic disease (1)(2)(3)(4)(5)(6)(7)(8). Investigations regarding sTfR as a measure of iron status in infants and children have provided promising results, including evidence that, in infants, sTfR concentrations may be superior to ferritin measurements in diagnosing ID (9). However, to date, concrete reference values and other decision-supporting limits for the commercially available methods have been virtually absent, and the age-relatedness of sTfR concentrations, although introduced as a concept, has not been unequivocally modeled statistically (10)(11)(12)(13)(14)(15). In this study we measured the sTfR concentrations from a selection of 301 healthy children, 6 months to 18 years of age, using a commercially available automated immunoturbidimetric assay. We then used a regression-based method to construct age-dependent 2.5% and 97.5% reference limits for sTfR as well as 95% confidence intervals for these limits in our population (16). The purpose was to demonstrate consistent age-dependent changes in sTfR concentrations and to establish appropriate reference limits to enable the use of sTfR measurements in routine pediatric clinical practice. A total of 301 children (130 boys and 171 girls; age range, 6 months to 18 years) were included in the healthy population of this study. The selection was made on the basis of detailed anamnesis and laboratory tests. Febrile episodes during the preceding 6 weeks, diet restrictions, chronic inflammatory or renal diseases, hematological diseases, recent iron supplementation, ongoing inflammation (C-reactive protein >10 mg/L; erythrocyte sedimentation rate >6 mm/h), anemia or abnormal red cell indices (17), and low ferritin concentrations (<10 …