title: Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections.
abstract: Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n= 21) and control (n= 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1-679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Monika.Wisniewska@charite.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Wisniewska
authors.affiliation: Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Malte.Cremer@charite.de.
authors.forename: Malte
authors.initials: M
authors.lastname: Cremer
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Lennart.Wiehe@charite.de.
authors.forename: Lennart
authors.initials: L
authors.lastname: Wiehe
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Niels-Peter.Becker@charite.de.
authors.forename: Niels-Peter
authors.initials: NP
authors.lastname: Becker
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Eddy.Rijntjes@charite.de.
authors.forename: Eddy
authors.initials: E
authors.lastname: Rijntjes
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Janine.Martitz@charite.de.
authors.forename: Janine
authors.initials: J
authors.lastname: Martitz
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Kostja.Renko@charite.de.
authors.forename: Kostja
authors.initials: K
authors.lastname: Renko
authors.affiliation: Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. christoph.buehrer@charite.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. lutz.schomburg@charite.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001724:Birth Weight; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006706:Homeostasis; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood* / Q000175:diagnosis; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D011446:Prospective Studies; D014131:Trace Elements / Q000097:blood; D015032:Zinc / Q000097:blood*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D014131:Trace Elements; D003300:Copper; D002097:C-Reactive Protein; D002570:Ceruloplasmin; D015032:Zinc
keywords: C reactive protein; ceruloplasmin; interleukin-6; micronutrient.; preterm