Tortora, Mario (2025) Serial prenatal MR imaging evaluation in valacyclovir-treated vs untreated CMV-infected fetuses. [Tesi di dottorato]

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Abstract

Introduction: A few studies have suggested modest benefits of reducing the severity of fetal infection when 8g/d of valacyclovir is administered during pregnancy from amniocentesis through delivery and found that valacyclovir increased the rate of asymptomatic neonates. We evaluated serial prenatal MR imaging data of infected fetuses who underwent in utero therapy to determine its possible effect on the appearance and progression of isolated brain “minor lesions”. Methods: Groups of in utero treated and untreated CMV-proven infected cases (diagnosed by using virus isolation and PCR technique in amniotic fluid) from mothers who seroconverted from the periconceptional period to 18 weeks GA, were selected. Two senior neuroradiologists with expertise in fetal MR imaging, reviewed all examinations together by consensus checking for the presence/absence of “minor polar temporal lesions". MRI data from treated and untreated fetuses were then compared considering the absence/presence of MRI signs of infection (Fisher exact test) and the time of appearance of the lesions (X2 test). Results: Among untreated fetuses (n=62), 23 (37.1%) never had any signs of infection (1st and 2nd negative MRIs), 32 showed signs of infection only on the 2nd MRI and 7 showed signs of infection already on the 1st MRI. Among treated fetuses (n=15) 11 (73.3%) never had any signs of infection, 4 showed signs of infection only on the 2nd MRI. The binary analysis (absence vs. presence of signs of infection) showed an absolute statistically significant difference (Fisher exact test p < 0.05) between the two groups: +36.2% in favor of the treated group. Treated fetuses were significantly more likely to not develop radiological signs than untreated fetuses (73.3% vs 37.1%; OR: 4.67, 95% CI 1.29-16.9; p=0.018). The three-category analysis (no lesions, early lesions, late lesions at MRI) confirmed the significant difference in distribution between the two groups (X2 p=0.02). Conclusions: Our preliminary data, although based on a limited number of cases, demonstrated a higher proportion of cases with consistently negative MR imaging findings and absence of early positivity in the group of treated fetuses, suggesting a beneficial effect of in utero treatment on the appearance of mild neuroradiological signs of infection.

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