Cytomegalovirus in pregnancy: 20-year experience of a southern italy centre on diagnosis, prenatal surveillance, and neonatal outcomes

Objective: To evaluate the epidemiology, diagnostic pathway, prenatal surveillance, and pregnancy outcomes of women referred for suspected cytomegalovirus (CMV) infection during pregnancy in a population-based cohort. Methods: This population-based cohort study included women counselled for suspected CMV infection during pregnancy between January 2002 and December 2021 in Campania, Italy. Maternal infection was classified as primary infection (documented seroconversion), suspected infection (IgG-positive/IgM-positive at first sample), or no infection during pregnancy, based on serial serology and IgG avidity testing. Prenatal diagnosis by amniocentesis for CMV DNA detection and serial ultrasound surveillance were offered in accordance with a standardized local protocol. Pregnancy and neonatal outcomes were recorded. Results: A total of 716 women were included. Primary CMV infection was documented in 320 women (44.7%), suspected infection in 58 (8.1%), and no CMV infection during pregnancy in 294 (41.1%); 44 cases (6.1%) were not classifiable due to incomplete follow-up. IgG avidity testing, available in 211 women, supported diagnosis but showed limited specificity for recent infection. Amniocentesis was performed in 209 cases (29.2%), with CMV DNA detected in 40 (19.1%); all PCR-positive cases were confirmed as congenital CMV infection at birth. Overall, 45 (6.3%) neonates were diagnosed with congenital CMV infection. The majority of infections (84.4%) occurred following early maternal primary infection. Prenatal ultrasound abnormalities were infrequent and heterogeneous; most infected neonates had negative prenatal scans. Several clinically significant neonatal sequelae, including sensorineural hearing loss and neurodevelopmental impairment, occurred in the absence of prenatal ultrasound findings. Conclusion: In this large population-based cohort, a substantial proportion of women referred for suspected CMV infection did not acquire infection during pregnancy, highlighting the need for careful interpretation of serological findings and centralized counselling. Primary infection, particularly when acquired early in pregnancy, remains the main determinant of congenital CMV infection and adverse outcomes. While amniocentesis is the most reliable prenatal diagnostic tool, ultrasound surveillance alone has limited sensitivity. These results provide a robust pre-treatment baseline for future studies evaluating the impact of maternal antiviral therapy with valaciclovir on vertical transmission and neonatal outcomes.