Hepcidin, an Iron Regulatory Hormone of Innate Immunity, is Differentially Expressed in Premature Fetuses with Early-Onset Neonatal Sepsis

Sammy M. Tabbah; Catalin S. Buhimschi; Katherine Rodewald-Millen; Christopher R. Pierson; Vineet Bhandari; Philip Samuels; Irina A. Buhimschi

doi:10.1055/s-0038-1626711

American Journal of Perinatology, Table of Contents

Am J Perinatol 2018; 35(09): 865-872
DOI: 10.1055/s-0038-1626711

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hepcidin, an Iron Regulatory Hormone of Innate Immunity, is Differentially Expressed in Premature Fetuses with Early-Onset Neonatal Sepsis

Authors

Sammy M. Tabbah

¹Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
Catalin S. Buhimschi

¹Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
Katherine Rodewald-Millen

¹Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
Christopher R. Pierson

²Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio

³Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio

⁴Department of Biomedical Education and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio
Vineet Bhandari

⁵Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania
Philip Samuels

¹Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
Irina A. Buhimschi

⁶Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio

⁷Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio

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

Full Text

References

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