Prohepcidin concentrations and erythroid progenitors in cord blood of appropriate versus small for gestational age neonates

Abstract

Objective: Prohepcidin (Pro-Hep), synthesized in the liver, is the prohormone of hepcidin (Hep), which reduces iron absorption in the gut; its synthesis is enhanced by inflammation and is reduced during hypoxia. We aimed to study the hypothesis that infants born small for gestational age (SGA) have reduced cord blood concentrations of Pro-Hep.Study Design: Cord blood was collected from 20 SGA (term and near term >35 week gestation) infants and 20 appropriate for gestational age (AGA) controls. We excluded infants exposed to maternal chronic diseases, smoking, diabetes, alcohol or drug use. Both groups had a 1 min Apgar score above or equal to 7 and had normal cord blood pH (above 7.25). ELISA was used to determine serum concentrations of Pro-Hep and erythropoietin (EPO). Circulating CD71 þ /CD45 À /SSC low cells were measured by flow cytometry as an index of erythroid progenitors.Result: There were no significant differences between groups in terms of hemoglobin concentrations, and Pro-Hep. In contrast, EPO levels and circulating CD71 þ /CD45 À /SSC low erythroid progenitors were significantly higher in the SGA group. These differences remained significant even after controlling for gestational age and gravidity.Conclusion: Contrary to EPO upregulation during intrauterine growth restriction (IUGR), and higher concentrations of circulating erythroid progenitors, Pro-Hep concentration is not affected by IUGR.

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

“… reported that small‐for‐gestational‐age (SGA) infants present with increased erythropoiesis, presumably due to hypoxia‐induced EPO production, but their cord blood pro‐hepcidin levels appear not to be affected by IUGR, despite higher concentrations of erythroid progenitors in the latter. The authors speculate that although fetal renal hypoxia in IUGR leads to EPO secretion, there might be no sufficient liver hypoxia to downregulate pro‐hepcidin production . Moreover, another study showed a positive correlation between pro‐hepcidin levels and birth weight in AGA, but not in SGA preterm infants.…”

Maternal iron status: relation to fetal growth, length of gestation, and iron endowment of the neonate

“…Mild maternal anemia is associated with increased serum erythropoietin in the mother 41,42 and in the cord 41,44 . Chronic fetal hypoxia from reduced uteroplacental blood flow increases hemoglobin production in the fetus via increased erythropoietin 45 and has been documented to occur in SGA infants 46 . Greater erythropoietin production may be the underlying reason for similar levels of hemoglobin in the cords of infants born to anemic and non‐anemic women, i.e., the erythropoietin enhances oxygen delivery and promotes the growth of fetal organs and tissues in a hypoxic environment.…”

“…41,44 Chronic fetal hypoxia from reduced uteroplacental blood flow increases hemoglobin production in the fetus via increased erythropoietin 45 and has been documented to occur in SGA infants. 46 Greater erythropoietin production may be the underlying reason for similar levels of hemoglobin in the cords of infants born to anemic and non-anemic women, i.e., the erythropoietin enhances oxygen delivery and promotes the growth of fetal organs and tissues in a hypoxic environment. Infants born at term with an appropriate weight for gestation have iron stores that are adequate for approximately 6 months, while those born preterm or who are SGA have smaller stores.…”

Hepcidin and Iron Metabolism in Pregnancy: Correlation with Smoking and Birth Weight and Length

“…The decreased concentration of this hormone in chronic obstructive pulmonary disease (CODP) patients and in healthy volunteers exposed to hypobaric hypoxia at high altitude was observed [ 35 , 36 ]. The remaining two suggested that prenatal, utero-placental chronic hypoxia reduced pro-hepcidin synthesis in the fetus [ 37 , 38 ]. Animal models demonstrate that increasing reactive oxygen species, especially H 2 O 2 , reduced expression of hepcidin mRNA as well as hepatic iron concentration [ 39 , 40 ].…”