Metabolomics Highlights Reduced Glutamate and Acetylcarnitine in the Amniotic Fluid of Cytomegalovirus-Infected Pregnant Women

Cytomegalovirus (CMV) is a major cause of morbidity in immunocompromised individuals and represents the leading infectious cause of neonatal congenital deafness. When acquired during pregnancy, CMV can be vertically transmitted to the fetus, potentially resulting in permanent sequelae characterized by intellectual and neurosensory impairments. To investigate metabolic alterations associated with primary maternal CMV infection, we conducted a metabolomics-based analysis of amniotic fluid (AF) from pregnant women who acquired CMV infection during the first trimester, as confirmed by IgG seroconversion, IgM positivity, and low-to-moderate IgG avidity indices. Our findings revealed that the AF metabolomic profiles from CMV transmitter and nontransmitter mothers were remarkably similar. In contrast, both the CMV-exposed groups showed profound metabolic dysregulation compared to uninfected controls, suggesting that CMV-related metabolic disparities may persist irrespective of vertical transmission. Specifically, we observed a significant downregulation of glutamate (<i>p</i> < 0.0001) and acetylcarnitine (<i>p</i> < 0.0001) in CMV groups compared to control AF samples. Notably, the combined reduction of these two metabolites emerged as a surrogate biomarker signature of recent primary CMV infection of the mother, indicating that AF from both transmitting and nontransmitting pregnancies may share common metabolic adaptations. These alterations may reflect early perturbations of neurobiochemical pathways with unknown effects on babies negative at birth, supporting the need for risk assessment and clinical monitoring even in the absence of congenital CMV infection.