Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis Mehmet Nevzat Cizmeci a,⇑ , Semra Kara a , Mehmet Kenan Kanburoglu a , Serap Simavli b , Candan Iltemur Duvan b , Mustafa Mansur Tatli a a Fatih University Medical School, Department of Pediatrics, Division of Neonatology, Turkey b Fatih University Medical School, Department of Obstetrics and Gynecology, Turkey article info Article history: Received 1 September 2013 Accepted 20 December 2013 abstract Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early rec- ognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism’s access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min–max: 118.1–8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysio- logic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis. Ó 2013 Elsevier Ltd. All rights reserved. Introduction Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity [1]. Although there is no single definition of the condition, EONS refers to an infection of the blood stream or meninges proven by culture. It is usually acquired vertically from the mother and manifests shortly after birth [2]. In very low birth weight infants, the rates of mortality due to EONS are as high as 40% [3]. However, symp- toms and laboratory markers of this serious condition are nonspe- cific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality [4]. Hepcidin, the key regulator of iron homeostasis, is a 25-amino- acid peptide molecule that is synthesized mainly by liver and excreted in urine [5]. It acts by modulating cellular iron export through an iron exporter, namely ferroportin, to plasma [6]. Hepci- din is homeostatically stimulated by iron excess and increased concentrations of this molecule block dietary iron absorption thus preventing iron loading [5,7]. Hepcidin is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism’s access to iron [4,8]. Since hepcidin is ex- pressed by macrophages and neutrophils in response to bacterial pathogens and its expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system [9–11]. Hypothesis The synthesis of hepcidin is induced by inflammation and infec- tion, and interleukin-6 was shown to be the major trigger for hep- cidin through a STAT3-dependent transcriptional mechanism [5]. An increase in urinary hepcidin concentration was demonstrated 2 h after infusion of IL-6 in human subjects [12]. Moreover, IL-1 was also shown to increase hepcidin mRNA in mouse hepatocytes 0306-9877/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mehy.2013.12.017 ⇑ Corresponding author. Address: Fatih University Medical School, Department of Pediatrics, Division of Neonatology, Alparslan Turkes Cad. No: 57, 06510 Emek, Ankara, Turkey. Tel.: +90 505 6576539; fax: +90 312 2213670. E-mail address: nevzatcizmeci@gmail.com (M.N. Cizmeci). Medical Hypotheses 82 (2014) 310–312 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy