Albertine Donker

Standardized Pediatric Hepcidin Values 235 7 RESULTS Characteristics of the study population Characteristics of the study population are described in Table 1 . Fifty-nine percent (n=157) of the total study population was male. Median age of males was 9 years (range 4 months – 17 years); median age of females 11 years (range 1 – 17 years). Hb, CRP and iron indicators for the different age groups (0 - < 2 years, 2 - < 6 years, 6 - < 12 years, 12-<18 years) are presented in Supplemental Table 1 . Data on blood sampling time of hepcidin and BMI of the participants are presented and discussed in Supplemental Figure 1 and Supplemental Figure 2 . Age- and sex-specific reference ranges for serum hepcidin concentrations Reference ranges (p25- p75) for serum hepcidin remained constant until the age of 12 years (independent median sample test, males p 0.886, females p 0.712) but were substantially lower after the age of 12 years in both males and females (independent sample median test, males p 0.003; females p 0.016) ( Table 2 and Supplemental Table 2 ). These results were confirmed with unadjusted univariable linear regression analysis for <12 years versus >12 years (males: β= -0.49; 95 % confidence interval [CI] -0.66– -0.31, females: β= -0.26; 95% CI -0.46– -0.05) ( Supplemental Table 3 ). Hepcidin concentration was below the detection limit of 0.5 nmol/l in 26 out of 157 males (17%) and 19 out of 109 females (17%) ( Table 2 ). The wide reference ranges reflect the substantial inter-individual variation of serum hepcidin concentrations. Because of the earlier described sex-specific differences in both adults and children 20,26,27,30,39 regarding serum hepcidin levels, all analyses were stratified for sex. As shown in Table 2 and Supplemental Table 2 , we did not observe a difference in serum hepcidin levels between males and females. Multivariate analysis including age, sampling time, BMI, sex, iron parameters, CRP and ALT confirmed that sex was not an independent correlate of serum hepcidin ( p 0.127).