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Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections
Monika Wisniewska1, Malte Cremer2, Lennart Wiehe3
1Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany. Monika.Wisniewska@charite.de.
Insights
Infections alter newborn trace element levels, reducing zinc and increasing copper. The copper/zinc ratio may serve as a key biomarker for early-onset infections in neonates.
Area of Science:
- Neonatal Medicine
- Trace Element Metabolism
- Biochemistry
Background:
- Copper (Cu) and zinc (Zn) are vital trace elements for infant development.
- Metabolic changes in these elements occur during acute infections, and deficiencies can heighten infection susceptibility.
Purpose of the Study:
- To investigate the impact of acute infections on copper and zinc homeostasis in newborns.
- To evaluate the potential of the copper/zinc ratio as a diagnostic biomarker for early-onset infections.
Main Methods:
- Prospective observational case-control study involving infected (n=21) and control (n=23) neonates.
- Analysis of trace element concentrations using X-ray fluorescence.
- Quantification of ceruloplasmin (CP) via Western blot.
Main Results:
- Copper levels increased in infected newborns from day 1 to day 3.
- A higher copper/zinc ratio was observed in infected newborns.
- The copper/zinc ratio correlated positively with C-reactive protein (CRP) levels.
Conclusions:
- Infections disrupt trace element balance in newborns, decreasing serum zinc while elevating copper and ceruloplasmin.
- The copper/zinc ratio effectively captures these alterations, showing independence from gestational age.
- This ratio shows promise as a diagnostic biomarker for early-onset neonatal 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.