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.

Background: Congenital cytomegalovirus (cCMV) is the most frequent infective cause of morbidity and long-term sequelae in infancy. Despite great attention to this clinical condition, potential prognostic factors for neurodevelopmental sequelae in cCMV patients are poorly understood, therefore hampering optimization of clinical care and management of cCMV patients. Methods: A retrospective single-center cohort study was conducted on 66 infants with congenital CMV infection in order to identify among clinical presentation at birth potential predictors of the absence of neurodevelopmental sequelae at 12 months of age. A logistic regression model was built in order to identify a correlation between potential predictors and neurodevelopmental status at one year of age in the cohort in the study. Results: The results of our study showed a significant correlation between normal neutrophil count and normal audiological assessment at birth in a logistic regression model (p < 0.05) in patients with cCMV with the absence of neurodevelopmental sequelae at M12. Our findings also underlined that normal platelet count and normal cerebral imaging are connected with normal neurodevelopment at one year of age, though not in a statistically significant way. Conclusions: Our findings underscore the need for appropriate assessment at birth in order to improve clinical management of cCMV patients.

Human milk is the optimal standard for neonatal nutrition, particularly for preterm infants. Several conditions associated with oxidative stress (OS) may be transmitted from mother to infant through milk, making the preservation of milk quality essential. When maternal milk is unavailable, donor human milk (DM) is commonly used and treated with Holder pasteurization (HoP) to ensure microbiological safety, although this process may affect bioactive components. This study aimed to evaluate the impact of HoP on OS biomarkers, specifically total antioxidant power (TAP) and 15-F2t-isoprostane, using colorimetric and ELISA methods as cost-effective alternatives to analytical gold standards. Twenty paired DM and HoP samples from the Human Milk Bank of Sant’Anna Hospital (Turin, Italy) were analyzed. No significant differences were observed in TAP levels between DM and HoP samples. In contrast, 15-F2t-isoprostane concentrations were significantly lower in DM compared to pasteurized milk (3.16 (1.59–5.27) vs. 0.76 (0.62–1.54), p-value < 0.001). This reduction remained consistent after stratification by sampling day. These findings suggest that HoP may reduce oxidative stress markers in donor milk, potentially limiting neonatal exposure to maternal oxidative imbalance. Although this effect could offer protective benefits for vulnerable preterm infants, further studies are needed to clarify the clinical implications of HoP on redox status and neonatal outcomes.