Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

Nutrients. 2017 Mar 30;9(4):343. doi: 10.3390/nu9040343.


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.

Keywords: C reactive protein; ceruloplasmin; interleukin-6; micronutrient.; preterm.

Publication types

  • Observational Study

MeSH terms

  • Biomarkers / blood*
  • Birth Weight
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Ceruloplasmin / metabolism
  • Copper / blood*
  • Female
  • Gestational Age
  • Homeostasis
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / blood*
  • Infant, Newborn, Diseases / diagnosis
  • Interleukin-6 / blood
  • Linear Models
  • Male
  • Prospective Studies
  • Trace Elements / blood
  • Zinc / blood*


  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Trace Elements
  • Copper
  • C-Reactive Protein
  • Ceruloplasmin
  • Zinc