Standardized serum hepcidin values in Dutch children: Set point relative to body iron changes during childhood

Abstract

Background: Use of serum hepcidin measurements in pediatrics would benefit from standardized age-and sex-specific reference ranges in children, in order to enable the establishment of clinical decision limits that are universally applicable. Procedure:We measured serum hepcidin-25 levels in 266 healthy Dutch children aged 0.3-17 years, using an isotope dilution mass spectrometry assay, standardized with our commutable secondary reference material (RM), assigned by a candidate primary RM. Results:We constructed age-and sex-specific values for serum hepcidin and its ratio with ferritin and transferrin saturation (TSAT). Serum hepcidin levels and hepcidin/ferritin and TSAT/hepcidin ratios were similar for both sexes. Serum hepcidin and hepcidin/ferritin ratio substantially declined after the age of 12 years and TSAT/hepcidin ratio gradually increased with increasing age. Serum hepcidin values for Dutch children <12 years (n = 170) and >12 years (n = 96) were 1.9 nmol/L (median); 0.1-13.1 nmol/L (p2.5-p97.5) and 0.9 nmol/L; 0.0-9.1 nmol/L, respectively. Serum ferritin was the most significant correlate of serum hepcidin in our study population, explaining 15.1% and 7.9% of variance in males and females, respectively. Multivariable linear regression analysis including age, blood sampling time, iron parameters, ALT, CRP, and body mass index as independent variables showed a statistically significant negative association between age as a dichotomous variable (≤12 vs >12 years) and log-transformed serum hepcidin levels in both sexes. Conclusions:We demonstrate that serum hepcidin relative to indicators of body iron is age dependent in children, suggesting that the set point of serum hepcidin relative to stored and circulating iron changes during childhood. K E Y W O R D Schild, ferritin, hepcidin, pediatric reference ranges, transferrin saturation

Plasma levels of osteopontin from birth to adulthood

“…Besides gender and age, factors during childhood development are well known to influence blood parameters 23 . Biomarkers and laboratory values in children are subject to age‐specific variability 24 …”

“…23 Biomarkers and laboratory values in children are subject to age-specific variability. 24 The availability of age-specific reference values is indispensable for a valid interpretation of the results of laboratory tests in children, since many biomarkers vary during the physiological development of a healthy child. [25][26][27] Most of the challenges encountered when establishing pediatric reference values are related to a growing and developing immune system that influences concentrations of various analytes routinely measured in clinical diagnostic laboratory.…”

Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia

“…Third, the sample size was restricted and there was a significant age difference between the IRIDA group and IDA control group, in which no children were included. In healthy non-iron deficient and non-anemic adults and children, the TSAT/hepcidin ratio seems to be comparable between adults and children <12 years, with a temporary increase in the ratio after the age of 12 years [29,30]. We hypothesized that this is due to a decrease in hepcidin levels in response to the increased production of gonadal hormones during adolescence, which might reflect a regulatory mechanism to adapt to the increased iron demands needed for rapid growth during puberty and to compensate for iron losses during menstrual bleeding in girls [30].…”

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes

“…In both groups, FID-patients were considerably younger and counted more non-Caucasians than patients with normal iron status. Since significant lower hepcidin concentrations were described in children older than 12 years, 31 it seems unlikely that a younger age contributed to not finding increased hepcidin concentrations in T1D children with FID. Lower hemoglobin concentrations and TSAT have been described in African-Americans compared to Caucasians, 32,33 and might explain why more non-Caucasians were found among FID-patients in the PHA-1 and PHA-2 group.…”