title: Fetal and early neonatal interleukin-6 response.
abstract: In 1998, a systemic fetal cytokine response, defined as a plasma interleukin-6 (IL-6) value above 11 pg/mL, was reported to be a major independent risk factor for the subsequent development of neonatal morbid events even after adjustments for gestational age and other confounders. Since then, the body of literature investigating the use of blood concentrations of IL-6 as a hallmark of the fetal inflammatory response syndrome (FIRS), a diagnostic marker of early-onset neonatal sepsis (EONS) and a risk predictor of white matter injury (WMI), has grown rapidly. In this article, we critically review: IL-6 biological functions; current evidence on the association between IL-6, preterm birth, FIRS and EONS; IL-6 reference intervals and dynamics in the early neonatal period; IL-6 response during the immediate postnatal period and perinatal confounders; accuracy and completeness of IL-6 diagnostic studies for EONS (according to the Standards for Reporting of Diagnostic Accuracy statement); and recent breakthroughs in the association between fetal blood IL-6, EONS, and WMI.
authors.affiliation: Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy. Electronic address: claudio.chiesa@ift.cnr.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Chiesa
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pacifico
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Natale
authors.affiliation: Research Unit for Neonatal Infectious Diseases and Epidemiology, Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, AT-8036 Graz, Austria.
authors.forename: Nora
authors.initials: N
authors.lastname: Hofer
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: John F
authors.initials: JF
authors.lastname: Osborn
authors.affiliation: Research Unit for Neonatal Infectious Diseases and Epidemiology, Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, AT-8036 Graz, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Resch
mesh_terms: D000068598:Data Accuracy; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005333:Fetus / Q000276:immunology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology / Q000502:physiology*; D056784:Leukoencephalopathies / Q000209:etiology; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology; D012016:Reference Values; D018805:Sepsis / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Diagnostic accuracy; Early-onset neonatal sepsis; Fetal inflammatory response syndrome; Interleukin-6; Reference intervals