Perinatal role of hepcidin and iron homeostasis in full-term intrauterine growth–restricted infants

Objectives To prospectively investigate iron homeostasis in full-term intrauterine growth–restricted (IUGR) and appropriate-for-gestational-age (AGA) infants at birth, by evaluating cord blood concentrations of hepcidin (a bioactive molecule, principal regulator of iron metabolism, downregulated by hypoxia/iron deficiency and upregulated by inflammation), erythropoietin (EPO, a marker of prolonged fetal hypoxia), soluble transferrin receptor (sTfR, a marker of increased erythropoiesis and tissue iron deficiency), iron, ferritin, and unsaturated iron-binding capacity (UIBC). Methods Serum cord blood samples from 47 well-defined IUGR and 104 AGA singleton, full-term infants were analyzed for concentrations of all the aforementioned parameters by enzyme immunoassays and spectrophotometry. Results Hepcidin concentrations were similar, while EPO concentrations were higher in IUGR cases than in AGA controls (P = 0.047). Cord blood sTfR concentrations were increased in IUGR, compared to AGA infants (P = 0.004), and negatively correlated with their customized centiles and birth weight (r = −0.238, P = 0.003 and r = −0.157, P = 0.050, respectively). Ferritin concentrations were lower in IUGR cases than in AGA controls (P = 0.039). In both groups, no correlations were observed between cord blood hepcidin concentrations and iron status indices. Conclusions Cord blood hepcidin concentrations in term IUGRs may remain unaffected, possibly due to a balance between hepcidin downregulation by chronic fetal hypoxia (indicated by higher EPO concentrations) and impaired iron metabolism (indicated by lower ferritin and higher sTfR concentrations) on the one hand, and hepcidin upregulation by the inflammatory state characterizing IUGRs, on the other. Furthermore, our findings may possibly indicate the need for regular follow-up for detection of iron-deficient anemia, not only in preterm but also in full-term IUGR neonates.