Primary HCMV infection in pregnancy from classic data towards metabolomics: An exploratory analysis.
BACKGROUND
Human cytomegalovirus (HCMV) is one of the most frequent risk of viral infections during pregnancy. The aim of this study was to evaluate the metabolic profile in amniotic fluid (AF) samples obtained from HCMV-infected, and uninfected fetuses in order to elucidate changes in metabolic pathways during congenital HCMV infection and to recognize new potential diagnostic and/or prognostic biomarkers.


METHODS
A retrospective cohort study was conducted on 63 pregnant women: 20 contracted primary HCMV infection during pregnancy and, subsequently, transmitted the virus to the fetus (transmitters); 20 contracted the infection without transmitting the virus to the fetus (non-transmitters); 23 who underwent amniocentesis for cytogenetic-based diagnosis were considered controls. Metabolomics analysis was performed by using the hyphenated technique Gas chromatography-mass spectrometry (GC-MS) followed by a multivariate statistical approach. Four PLS-DA models were generated: controls vs. transmitters; controls vs. non-transmitters; transmitters vs. non-transmitters; and asymptomatic infected vs. symptomatic infected newborns. Subsequently, these models were exploited for network mapping.


RESULTS
Compared with controls, HCMV transmitters showed significantly increased levels in glutamine, glycine, serine, pyruvic acid, threonine, threonic acid, and cystine; conversely, unknown U1715 and U1804, glutamic acid, U1437, fructose, sugar-like A203003 and A203005, and tyrosine levels were found decreased. In non-transmitters, glutamine, serine, glycine, threonic acid, threonine, 1-monostearin, urea, and cystine were found increased, while sorbitol, unknown U1804, sugar-like A203003, U1751, xylitol, leucine and fructose were decreased. The comparison between transmitters and non-transmitters did not produce a statistically significant model. Unlike controls' profile, a common feature of HCMV infected subjects (transmitters and non-transmitters) was the activation of glutamine-glutamate and pyrimidine metabolic pathways. In addition, a clusterization for asymptomatic vs. symptomatic outcome was also observed due to alteration of fatty acids biosynthesis.


CONCLUSIONS
Metabolomics approach could highlight the significant modification of maternal and placental status during HCMV infection for both transmitter and non-transmitter subjects. A further separation was observed for asymptomatic vs. symptomatic HCMV congenital infections model. Therefore, metabolomics may be a promising tool to improve the accuracy of an early diagnosis, and the management of HCMV pregnancy-related infections.
Department of Chemical and Geological Sciences, University of Cagliari, Cagliari I-09042, Italy.
Claudia
C
Fattuoni
Department of Chemical and Geological Sciences, University of Cagliari, Cagliari I-09042, Italy.
Francesco
F
Palmas
Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari I-09042, Italy.
Antonio
A
Noto
Department of Public Health Clinical and Molecular Medicine, University of Cagliari, Cagliari I-09042, Italy.
Luigi
L
Barberini
Laboratory Medicine Service, IRCCS AOU San Martino-IST, University-Hospital, Genoa, Italy. Electronic address: michele.mussap@hsanmartino.it.
Michele
M
Mussap
CDS Creative Data Solutions, Ballwin, MO, USA.
Dmitry
D
Grapov
Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari I-09042, Italy.
Angelica
A
Dessì
Department of Chemical and Geological Sciences, University of Cagliari, Cagliari I-09042, Italy.
Mariano
M
Casu
Department of Public Health Clinical and Molecular Medicine, University of Cagliari, Cagliari I-09042, Italy.
Andrea
A
Casanova
Molecular Virology Unit, Microbiology and VirologyDepartment, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Milena
M
Furione
Departments of Obstetrics and Gynecology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Alessia
A
Arossa
Departments of Obstetrics and Gynecology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Arsenio
A
Spinillo
Molecular Virology Unit, Microbiology and VirologyDepartment, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Fausto
F
Baldanti
Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari I-09042, Italy.
Vassilios
V
Fanos
Molecular Virology Unit, Microbiology and VirologyDepartment, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Maurizio
M
Zavattoni
D000328:Adult; D000653:Amniotic Fluid / Q000821:virology; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005260:Female; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism* / Q000821:virology; D012189:Retrospective Studies
Amniotic fluid; Biomarkers; Gas chromatography-mass spectrometry (GC–MS); Human cytomegalovirus (HCMV); Metabolomics; Network analysis