Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3-15 Years

Background: Reference values of ferritin and transferrin for European children do not exist. Objective: We aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15- y-old children based on cohort data and to investigate determinants of iron status. Methods: A total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using crosssectional and longitudinal data. Results: The age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 mu g/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: beta = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: beta = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 mu g/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin crosssectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. Conclusions: Age-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.