Post-transfusion changes in serum hepcidin and iron parameters in
and Lydia Kossiva
Neonatal Intensive Care Unit and
Research Laboratory of Clinical Biochemistry–Molecular Diagnostics,
Department of Pediatrics, National and Kapodistrian University of Athens, P&A Kyriakou Children’s Hospital and
Laboratory of Biochemistry, P&A Kyriakou Children’s Hospital, Athens, Greece
Abstract Background: Packed red blood cell transfusion is common in preterm neonates. Hepcidin acts as a negative feed-
back iron regulator. Iron parameters such as immature reticulocyte fraction (IRF) and high-light-scatter reticulocytes
(HLR) are used to clarify iron metabolism. Very little is known about the regulation of hepcidin in preterm infants
because most reports have evaluated prohepcidin. The aim of this study was therefore to evaluate serum hepcidin
and establish hematological parameters in preterm infants after transfusion.
Methods: The subjects consisted of 19 newborns (10 boys) with mean gestational age 29.1 Æ 2.0 weeks, who had
been transfused at the chronological age of 44.84 Æ 19.61 days. Blood sample was collected before the transfusion
and thereafter at 5 days and at 1 month. Serum hepcidin and other iron parameters were evaluated.
Results: Mean serum hepcidin before and 5 days after transfusion was signiﬁcantly different (5.5 Æ 5.1 vs 10 Æ
7.9 ng/mL respectively, P = 0.005). IRF and % HLR were also decreased signiﬁcantly, 5 days after transfusion (0.4
Æ 0.2 vs 0.2 Æ 0.1, P = 0.009; 1.4 Æ 1.5% vs 0.5 Æ 0.4%, P = 0.012, respectively). Changes in hepcidin 5 days
after transfusion were correlated signiﬁcantly with changes in mean corpuscular hemoglobin (b, 0.13; SE, 0.05; P =
0.017), total iron binding capacity (b, 3.74; SE, 1.56; P = 0.016) and transferrin (b, 2.9, SE, 1.4; P = 0.039).
Conclusions: Serum hepcidin concentration, along with IRF and HLR, are potentially useful in estimating pre- and
post-transfusion iron status. Larger studies are needed to evaluate the sensitivity and speciﬁcity of hepcidin com-
pared with ordinary iron parameters in premature infants.
Key words anemia, hepcidin, iron metabolism, prematurity, transfusion.
Iron is an essential micronutrient that plays a signiﬁcant role
in critical cellular functions. Anemia and iron deﬁciency are
very common in neonatal intensive care units. Compromised
iron stores combined with rapid growth, accelerated erythro-
poiesis and frequent blood sampling render preterm neonates
at high risk for iron deﬁciency and consequent anemia. Even
though most hospitalized premature infants require red blood
cell (RBC) transfusions, little is known about the way transfu-
sions alter the iron status in those newborns.
Hepcidin acts as a negative feedback regulator of iron
homeostasis by binding to ferroportin, inducing internaliza-
tion and degradation of ferroportin, leading to limited iron
entry into the extracellular ﬂuid. Several factors are known
to inﬂuence hepcidin expression such as inﬂammatory
cytokines, plasma iron level, anemia and hypoxia.
of our knowledge on iron homeostasis is based on studies of
animal models or adult humans. Currently very little is
known about the regulation of hepcidin production in neo-
nates, especially preterm ones. Immature reticulocyte fraction
(IRF) and high-light-scatter reticulocytes (HLR) are two rela-
tively new reticulocyte parameters that reﬂect potential bone
marrow erythropoiesis. IRF is a reliable indicator of erythro-
poietic rate because it refers to more immature reticulocytes
with higher RNA content.
tion. The higher the light scatter, the more immature the
The aim of this study was therefore to measure serum hep-
cidin in preterm neonates with anemia of prematurity before
and after a single erythrocyte transfusion and explore the pos-
sible relationships between hepcidin level, serum iron, com-
plete blood count (CBC) and other parameters involved in
iron metabolism in those infants.
This prospective study was carried out in the neonatal unit of
P&A Kyriakou Children’s Hospital in Athens, during a 1 year
period (2013). The Hospital’s Ethics Committee approved the
study protocol. Written informed consent was obtained from
the parents of all participants.
Correspondence: Lydia Kossiva, MD PhD, Second Department of
Pediatrics, National and Kapodistrian University of Athens, P&A
Kyriakou Children’s Hospital, Thevon and Levadias Street, Goudi
11527, Athens, Greece. Email: email@example.com
Received 2 March 2017; revised 16 July 2017; accepted 22
© 2017 Japan Pediatric Society
Pediatrics International (2018) 60, 148–152 doi: 10.1111/ped.13478