Abstract
Objective Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading
to functional hypoferremia through intracellular iron sequestration. We explored hepcidin–ferroportin
interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS).
Study Design Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay
(ELISA) in 92 paired cord blood–maternal blood samples in the following groups: “Yes”
EONS (n = 41, gestational age [GA] 29 ± 1 weeks) and “No” EONS (n = 51, GA 26 ± 1 weeks). Placental hepcidin and ferroportin expression were evaluated
by immunohistochemistry and real-time-polymerase chain reaction (RT-PCR). Liver hepcidin
and ferroportin expression patterns were ascertained in autopsy specimens of neonates
(n = 8) who died secondary to culture-proven sepsis.
Results Cord blood hepcidin was significantly elevated (GA corrected, p = 0.018) and was positively correlated with IL-6 (r = 0.379, p = 0.001) in EONS. Hepcidin localized at syncytiotrophoblast and fetal vascular endothelium.
Placental ferroportin, but not hepcidin mRNA correlated with cord blood hepcidin levels
(r = 0.46, p = 0.039) and funisitis severity (r = 0.50, p = 0.018). Newborns who died from sepsis (n = 4) had higher hepatic hepcidin and iron sequestration, but lower ferroportin staining
than those who died of nonsepsis causes (n = 4).
Conclusion Premature fetuses with EONS have elevated circulating hepcidin, likely related to
lower placenta and liver ferroportin expression. Fetal hepcidin–ferroportin interaction
appears to play a role in EONS pathophysiology independent of maternal response to
intrauterine inflammation.
Keywords
chorioamnionitis - funisitis - placenta - cord blood
