Background As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs).
Objectives To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection.
Methods More than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters.
Results Congenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens.
Conclusions Implementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine development.
- Congenital cytomegalovirus infection
- newborn screening
- urine filter paper
- multicentre study
- risk of infection
- infectious diseases
- maternal medicine
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To cite: Koyano S, Inoue N, Oka A, et al. Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study. BMJ Open 2011;1:000118. doi:10.1136/bmjopen-2011-000118
This study was presented in part at the Congenital Cytomegalovirus Workshop, 22–24 September 2010, Paris, France.
Funding This work was supported by Grants for the Research on Child Development and Diseases (H20-Kodomo-007; H23-Jisedai-Ippan-001) from the Ministry of Health, Labour and Welfare, Japan.
Competing interests None.
Patient consent Obtained from the parents.
Ethics approval Ethics approval was provided by the Ethical Committee on Human Subjects of each participating institute.
Contributors SK, NI and K Fujieda (deceased) designed the study. SK and K Fujieda (deceased) coordinated operations at the study sites. SK and NI had full access to all of the data in this study and take responsibility for the integrity of the data and accuracy of the data analysis. SK, AO, HM, KA, YI, HY and TY enrolled newborns and acquired medical data. NI conducted all initial screening, and TS performed serological tests. NI drafted the manuscripts, and all others provided important intellectual input for revision of the manuscript.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Technical details of the screening assay and some of the raw dataset for the tables presented in the manuscript are available from the corresponding author at . Consent for data sharing was not obtained from the parent(s), but the presented data are anonymised, and the risk of identification is low.
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