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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

Sammy M. Tabbah
1   Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
,
Catalin S. Buhimschi
1   Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
,
Katherine Rodewald-Millen
1   Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
,
Christopher R. Pierson
2   Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio
3   Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio
4   Department of Biomedical Education and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio
,
Vineet Bhandari
5   Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania
,
Philip Samuels
1   Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
,
Irina A. Buhimschi
6   Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio
7   Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio
› Author Affiliations Funding This work was supported by grants from National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD062007 (C.S.B. and I.A.B.) and R01HD047321 (I.A.B.). In addition, the Division of Maternal Fetal Medicine of The Ohio State University College of Medicine and The Center for Perinatal Research of The Research Institute at Nationwide Children's Hospital participated with funds allocated for MFM fellow research projects. The funding sources had no involvement in study design, interpretation of data, writing of the report, or decision to submit the paper for publication.
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Publication History

19 December 2017

29 December 2017

Publication Date:
02 February 2018 (online)

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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
 

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