Protein Biomarkers and Host RNA Expression Profiles in Congenital Cytomegalovirus Infection
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
연락처 및 위치
연구 연락처
- 이름: Kia Hee Schultz Dungu, MD
- 전화번호: +45 22645782
- 이메일: kia.hee.schultz.dungu@regionh.dk
연구 연락처 백업
- 이름: Ulrikka Nygaard, Ass Prof PhD
- 전화번호: +45 35459761
- 이메일: Ulrikka.Nygaard@regionh.dk
연구 장소
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Copenhagen, 덴마크, 2100
- 모병
- Department of Paediatrics and Adolescent Medicine, Rigshospitalet
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연락하다:
- Kia Hee Schultz Dungu, MD
- 전화번호: +45 22645782
- 이메일: kia.hee.schultz.dungu@regionh.dk
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Copenhagen, 덴마크, 2300
- 모병
- Department of Congenital Disorders, Statens Serum Institut
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연락하다:
- David M Hougaard, D.Sc (med)
- 전화번호: +45 32683544
- 이메일: dh@ssi.dk
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
건강한 자원 봉사자를 받아들입니다
샘플링 방법
연구 인구
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
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Cases
300 children with symptomatic congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
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Control group 1
300 children without congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
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Control group 2
30 neonates with asymptomatic congenital CMV infection and no sequelae Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Differential protein expression associated with sequelae following congenital cytomegalovirus infection
기간: At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Normalized protein expression levels measured by Olink proteomics in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Differential host RNA expression associated with sequelae following congenital cytomegalovirus infection
기간: At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Host RNA expression profiles measured in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Immune pathway enrichment based on proteomic and RNA expression profiles
기간: At neonatal dried blood spot collection (typically 2-3 days after birth).
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Immune and inflammatory pathways will be assessed by host RNA expression and normalized protein expression levels measured in neonatal dried blood spot samples.
Pathway enrichment analyses will be used to identify biological pathways associated with congenital cytomegalovirus infection and subsequent sequelae.
Exploratory comparisons will be made with previously published host RNA expression signatures related to infectious disease and immune responses.
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At neonatal dried blood spot collection (typically 2-3 days after birth).
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공동 작업자 및 조사자
수사관
- 수석 연구원: Kia Hee Schultz Dungu, MD, Rigshospitalet, Denmark
- 연구 의자: Ulrikka Nygaard, Ass Prof PhD, Rigshospitalet, Denmark
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- H-21009288-CMV
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
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