Temporal trends in the clinical presentation, management, and outcomes of children with congenital cytomegalovirus infection.

Abstract

Congenital cytomegalovirus (cCMV) is the most common congenital infection and a leading cause of sensorineural hearing loss as well as neurodevelopmental impairment. In recent years, awareness, screening, and management strategies for cCMV have evolved. This study aimed to assess temporal changes in the clinical presentation, treatment, and outcomes of children diagnosed with cCMV infection. We conducted a retrospective cohort analysis using data from the CCMVnet registry ( www.ccmvnet.org ), an international multicenter database collecting anonymized data on children with confirmed cCMV infection. A total of 1653 patients diagnosed between 2011 and 2024 were included and divided into two cohorts: 2011-2016 (n = 566) and 2017-2024 (n = 1087). The year 2017 was selected as a pragmatic cutoff, corresponding to the year of publication of the European expert consensus statement on congenital CMV. Children were identified through antenatal, clinical, hearing-related, and newborn screening pathways. Symptomatic cCMV at birth was defined by the presence of at least one predefined clinical, laboratory, hearing, or neuroimaging finding based on previously published criteria. A comparative analysis between two distinct time periods was conducted, encompassing neonatal clinical findings, neuroimaging results, treatment strategies, and long-term outcomes. Newborns classified as symptomatic at birth decreased in the more recent cohort, from 49.2% in P1 to 44.2% in P2 (p = 0.07). The use of intravenous ganciclovir decreased from 7.3% to 2.8% (p < 0.001), while the use of oral valganciclovir alone increased from 43.8% to 78.7% (p < 0.001). Differences in long-term outcomes were observed between the two periods, with motor impairment at 12 months decreasing from 16.5% to 6.2% (p < 0.001) and any long-term sequelae at 36 months decreasing from 40.0% to 31.0% (p = 0.05).

Conclusion:  This study highlights temporal differences in the clinical spectrum, management, and outcomes of children with congenital CMV infection in Europe. The higher proportion of asymptomatic and mildly symptomatic children in the latter period may reflect changes in maternal and neonatal screening practices. The observed temporal differences provide insight into the evolving clinical landscape of cCMV diagnosis and management, while their underlying causes cannot be determined from the present data.

What is known: • Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of sensorineural hearing loss and neurodevelopmental impairment in children. • Clinical management of cCMV has evolved substantially over the last decade, particularly following the publication of the European expert consensus statement in 2017 and alongside expanding screening strategies.

What is new: • In our cohort, children diagnosed with cCMV after 2017 presented with milder clinical manifestations and experienced fewer long-term sequelae than those diagnosed before 2017. • Temporal changes in diagnostic pathways, treatment practices, and clinical outcomes were observed between the two study periods.