1H NMR Urinary Metabolomics Profiling of Newborns with Congenital Human Cytomegalovirus Infection: Insights into Metabolic Alterations

TL;DR

This study uses 1H NMR to identify distinct urine metabolite patterns in newborns with congenital cytomegalovirus infection compared to healthy controls.

Contribution

The study introduces urinary metabolomics as a novel diagnostic and prognostic tool for congenital cytomegalovirus infection in newborns.

Findings

Newborns with cCMV had elevated levels of betaine, citrate, and several other metabolites in urine.

Healthy controls showed higher levels of creatine, creatinine, and taurine in their urine.

Metabolomic profiling accurately distinguished infected and uninfected newborns with high accuracy.

Abstract

Human cytomegalovirus (HCMV) is the leading cause of
congenital
infections resulting in severe morbidity and mortality among newborns
worldwide. Currently, the most significant prognostic factor of congenital
cytomegalovirus (cCMV) infection is the time of maternal infection,
with a more severe clinical phenotype if the mother’s first
outbreak occurs during the first trimester of pregnancy. Nonetheless,
the pathogenesis of cCMV infection has still to be completely characterized.
In particular, little is known about the metabolic response triggered
by HCMV in congenitally infected newborns. As such, urinary metabolic
profiling by 1H nuclear magnetic resonance (NMR) might
represent a promising tool to be exploited in the context of cCMV.
This study aims to investigate the impact of HCMV infection on the
urine metabolome in a population of congenitally infected newborns
and uninfected controls by 1H NMR spectroscopy combined
with multivariate statistical analysis. The 1H NMR spectra
of patients (n = 35) and controls (n = 15) allowed the identification of an overall amount of 55 metabolites.
Principal Component Analysis (PCA) and clustering correctly assigned
49 out of 50 newborns into the infected and control groups. Partial
Least-Squares-Discriminant Analysis (PLS-DA) revealed that newborns
with cCMV resulted in having increased betaine, citrate, 3-hydroxybutyrate,
4-hydroxybutyrate, acetoacetate, formate, glycolate, lactate, succinate,
and threonine levels in the urine. On the other hand, healthy controls
showed increased 4-aminohippurate, creatine, creatinine, fumarate,
mannitol, taurine, and dimethylamine levels. These results showed
a clear difference in metabolomic fingerprint between newborns with
cCMV infection and healthy controls. Thus, metabolomics can be considered
a new, promising diagnostic and prognostic tool in the clinical management
of cCMV patients.

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