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Published on: July 6, 2013
[Therapy Options for Infants with Congenital Cytomegalovirus Infection - Implications for Setting Up Neonatal
Christoph Bührer1, Oliver Blankenstein2, Rainer Rossi3
1Klinik für Neonatologie, Charité - Universitätsmedizin Berlin, Berlin.
Insights
Antiviral treatment for congenital cytomegalovirus (CMV) infection in newborns with mild symptoms, including hearing loss, is debated. More research is needed to establish a standard therapy before widespread screening for congenital CMV infection is implemented.
Area of Science:
- Neonatal screening and infectious diseases
- Pediatric infectious disease management
- Clinical trial methodology
Background:
- Neonatal screening in Germany expanded from one disease in 1968 to 17 by 2018.
- Potential harm from treating screened disorders is highlighted by failed neuroblastoma screening.
- Pilot studies for congenital cytomegalovirus (CMV) infection exist, but treatment consensus is lacking.
Purpose of the Study:
- To systematically review existing studies on the therapy of congenital CMV infection.
- To evaluate the efficacy of different antiviral treatments for congenital CMV infection in infants.
Main Methods:
- Systematic literature search using PubMed and WHO ICTRP.
- Analysis of controlled trials and registry data on congenital CMV infection treatment.
Main Results:
- One trial showed intravenous ganciclovir reduced hearing deterioration in symptomatic infants.
- Valganciclovir treatment duration (6 weeks vs. 6 months) showed no hearing benefit but improved development with longer treatment.
- A 12-month valganciclovir regimen in an open-label registry led to hearing improvement in 2/3 of infants with isolated hearing loss.
Conclusions:
- Therapy for neonates with congenital CMV infection and mild symptoms, like isolated hearing loss, remains controversial.
- Establishing a universally accepted treatment is crucial before implementing universal or targeted screening for congenital CMV infection.
Introduction:
The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified.
Methodology:
Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP).
Results:
We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years.
Conclusions:
Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.
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