Protein Biomarkers and Host RNA Expression Profiles in Congenital Cytomegalovirus Infection
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Congenital Cytomegalovirus, Cytomegalovirus Infections, Neonatal Infection, Sensorineural Hearing Loss. Basic parameters: 0 Days — 28 Days · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Denmark
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This study seeks to identify and test host protein biomarkers and RNA expression profiles in dried blood spot samples as novel diagnostic markers of congenital cytomegalovirus sequelae and to improve the understanding of the pathogenesis of the disease.
Detailed description
Background:
Human cytomegalovirus (CMV) is one of the most common causes of congenital viral infection, leading to a significant number of children with permanent disabilities. It is recognized as the major infectious cause of sensorineural hearing loss (SNHL) and neurodevelopmental abnormalities in infants. Its pathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. In Western Europe the incidence is estimated to 0.5-0.7% of all live births. In Denmark there are 240-480 children born every year with CMV infection, but the incidence has not been studied since 1979. Among the congenitally infected infants, approximately 10% are estimated to have symptoms at birth, ranging from mild, such as petechiae, to severe, such as microcephaly. Approximately half of these symptomatic children develop permanent long-term disabilities, such as hearing loss, cognitive and motor developmental delay. Asymptomatic children are also at risk for CMV-related disabilities, and 10-15% will develop SNHL. SNHL after congenital CMV infection may be present at birth or occur later in childhood and therefore, a significant part of these will not be detected in time for diagnosis and appropriate treatment, e.g., ganciclovir within the first 30 days of life. At present, there is no reliable virological marker to determine which infants will develop sequelae.
Method:
A nationwide retrospective case-control study of all neonates with congenital CMV infection in Denmark from 2010 through 2025. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. Proteomic analyses and RNA sequencing will be performed at the Department for Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of neonates matched on gestational age, sex, birthweight and age at DBS sample collection.
Perspectives:
New molecular-based diagnostic tools may contribute to improve early diagnosis and treatment of infants with congenital CMV infection and potentially prevent development of sequelae. Additionally, understanding of the pathogenesis at a molecular level of severe disease manifestations of the disease, could form the basis for development of novel interventions for better prevention and treatment.
Primary outcome measures
- Differential protein expression associated with sequelae following congenital cytomegalovirus infection [Time frame: At neonatal dried blood spot sampling (typically 2-3 days after birth).]
- Differential host RNA expression associated with sequelae following congenital cytomegalovirus infection [Time frame: At neonatal dried blood spot sampling (typically 2-3 days after birth).]
Secondary outcome measures (1)
- Immune pathway enrichment based on proteomic and RNA expression profiles [Time frame: At neonatal dried blood spot collection (typically 2-3 days after birth).]
Eligibility criteria
Inclusion criteria
- Children born between 1 January 2010 and 31 December 2025 with an available neonatal dried blood spot sample collected through the Danish National Newborn Screening Program.
- Cases: children with verified congenital CMV infection, defined as a positive CMV PCR result on neonatal dried blood spot, blood, or urine collected within the neonatal period.
- Controls: children without evidence of congenital CMV infection selected from the same newborn screening population and matched to cases on sex, gestational age, birthweight, and age at DBS sampling.
Exclusion criteria
- DBS samples not approved for research use.
- DBS samples with insufficient blood material for RNA expression profiling and/or proteomic analyses.
- Samples with inadequate analytical quality for molecular or proteomic analyses.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Denmark · 2 centers
- Department of Paediatrics and Adolescent Medicine, Rigshospitalet — Copenhagen
- Department of Congenital Disorders, Statens Serum Institut — Copenhagen
Identifiers
NCT: NCT07635368 · H-21009288-CMV