The Utility of Serum Hepcidin as a Biomarker for Late-Onset Neonatal Sepsis

Division of Neonatology, University of Southern California Keck School of Medicine, Los Angeles, CA.
The Journal of pediatrics (Impact Factor: 3.79). 07/2012; 162(1). DOI: 10.1016/j.jpeds.2012.06.010
Source: PubMed


To assess the utility of hepcidin, a potent regulator of host defense and inflammation, in the diagnosis of late-onset sepsis in very low birth weight infants.

Study design:
We compared the diagnostic performance of hepcidin with C-reactive protein from the serum concentrations in acute and convalescent blood specimens obtained from 44 infants suspected of late-onset sepsis. The predictive accuracies were assessed from the areas under receiver operating characteristic curves and the cutoffs that differentiated infants with and without sepsis were identified using classification and regression tree analysis.

Seventeen of the enrolled infants in this study were bacteremic and/or received antibiotics for neonatal sepsis for ≥ 5 days (infants with sepsis). The concentrations of hepcidin were increased 4-fold in infants with compared with infants without sepsis (P < .0001) and returned to similar levels following therapy. The areas under receiver operating characteristic curves of hepcidin was 0.93 compared with 0.83 for C-reactive protein, P = .06. Hepcidin concentration >92.2 ng/mL correctly classified 91% of all infants (positive predictive value: 100%, negative predictive value: 87%, specificity: 100%, and sensitivity: 76%).

Serum hepcidin concentration may be a useful adjunct test, in addition to blood culture and other markers of infection, in the evaluation of late-onset sepsis in very low birth weight infants.

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Available from: Tai-Wei Wu, Aug 21, 2014
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    • "The use of serum hepcidin level as an index for ID has been tested in adult populations [8-11]. However, very few studies have investigated the effectiveness of serum hepcidin measurements in children [12-14]. Furthermore, the sensitivities and specificities of various serum hepcidin cutoff levels in the diagnosis of ID have not been determined in either adults or children. "
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    ABSTRACT: Iron deficiency (ID) and iron deficiency anemia (IDA) are common nutritional disorders in children. Hepcidin, a peptide hormone produced in the liver, is a central regulator of systemic iron metabolism. We evaluated whether serum hepcidin levels can diagnose ID in children. Sera from 59 children (23 males and 36 females; 5 months to 17 years) were analyzed for hepcidin-25 by ELISA. Patients were classified according to hemoglobin level and iron parameters as: IDA, (N=17), ID (N=18), and control (N=24). Serum hepcidin, ferritin, soluble transferrin receptor (sTfR), transferrin saturation, and hemoglobin levels differed significantly between groups (P<0.0001). Serum hepcidin and ferritin levels (mean±SD) were 2.01±2.30 and 7.00±7.86, 7.72±8.03 and 29.35±24.01, 16.71±14.74 and 46.40±43.57 ng/mL in the IDA, ID, and control groups, respectively. The area under the receiver operating characteristic curve for serum hepcidin as a predictor of ID was 0.852 (95% CI, 0.755-0.950). Hepcidin ≤6.895 ng/mL had a sensitivity of 79.2% and specificity of 82.8% for the diagnosis of ID. Serum hepcidin levels were significantly correlated with ferritin, transferrin saturation, and hemoglobin levels and significantly negatively correlated with sTfR level and total iron binding capacity (P<0.0001). Serum hepcidin levels are significantly associated with iron status and can be a useful indicator of ID. Further studies are necessary to validate these findings and determine a reliable cutoff value in children.
    The Korean journal of hematology 12/2012; 47(4):286-92. DOI:10.5045/kjh.2012.47.4.286
  • C L Liu · H W Ai · W P Wang · L Chen · H B Hu · T Ye · X H Zhu · F Wang · Y L Liao · Y Wang · [...] · L Xu · M Sun · C Jian · Z J Chen · L Li · B Zhang · L Tian · B Wang · S Yan · Z Y Sun
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    ABSTRACT: Septicemia is a common cause of morbidity and mortality among newborns in the developing world. However, accurate clinical diagnosis of neonatal sepsis is often difficult because symptoms and signs are often nonspecific. Blood culture has been the gold standard for confirmation of the diagnosis. However, the sensitivity is low and results are usually not promptly obtained. Therefore, the diagnosis of sepsis is often based on clinical signs in association with laboratory tests such as platelets count, immature/total neutrophils ratio (I/T), and a rise in C-reactive protein (CRP). Polymerase chain reaction (PCR) methods for the detection of neonatal sepsis represent new diagnostic tools for the early identification of pathogens. During a 4-month prospective study, 16S rRNA PCR was compared with conventional blood culture for the diagnosis of neonatal bacterial sepsis. In addition, the relationship between known risk factors, clinical signs, laboratory parameters, and the diagnosis of sepsis was considered. Sepsis was suspected in 706 infants from the intensive neonatal care unit. They all were included in the study. The number of positive cultures and positive PCR results were 95 (13.5%) and 123 (17.4%), respectively. Compared with blood culture, the diagnosis of bacterial sepsis by PCR revealed a 100.0% sensitivity, 95.4% specificity, 77.2% positive predictive value, and 100.0% negative predictive value. In this study, Apgar scores at 5min, weight, icterus, irritability, feeding difficulties, gestational age (GA), premature rupture of membrane (PRM), platelets count, I/T, and a marked rise in CRP were important in establishing the diagnosis of sepsis in the newborn. In addition, weight, GA, PRM, irritability, duration of antibiotic usage, mortality rate, and number of purulent meningitis cases were significantly different between early-onset sepsis and late-onset sepsis. 16S rRNA PCR increased the sensitivity in detecting bacterial DNA in newborns with signs of sepsis, allowed a rapid detection of the pathogens, and led to shorter antibiotic courses. However, uncertainty about the bacterial cause of sepsis was not reduced by this method. 16S rRNA PCR needs to be further developed and improved. Blood culture is currently irreplaceable, since pure isolates are essential for antimicrobial drug susceptibility testing.
    Archives de Pédiatrie 12/2013; 21(2). DOI:10.1016/j.arcped.2013.11.015 · 0.41 Impact Factor
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    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 recognition 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: 118.1-8400ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis.
    Medical Hypotheses 12/2013; 82(3). DOI:10.1016/j.mehy.2013.12.017 · 1.07 Impact Factor
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