Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study

Abstract

BackgroundAs 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).ObjectivesTo 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.MethodsMore 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.ResultsCongenital 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.ConclusionsImplementation 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.

Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening

“…These patients might otherwise not have been diagnosed with congenital CMV infection, because typical clinical manifestations such as microcephaly and hepatosplenomegaly were absent. In the recent universal CMV screening conducted in Japan, CMV was identified in 0.3% of newborns, and SNHL was observed in 12% of infected cases [15]. If these frequencies are applied to our study population, the predicted number of congenital CMV-related SNHL is 7.5, which is close to the number of cases identified in this study.…”

Time-Series Analysis Comparing the Prevalence of Antibodies against Nine Viral Species Found in Umbilical Cord Blood in Japan

“…CMV is the most common congenital viral infection, with a birth prevalence of about 0.2z-2.2z in developed countries and 0.31z in Japan (1,2,15). Congenital CMV infection causes significant clinical consequences not only at birth but also later, presenting as neurological sequelae, including sensorineural hearing loss and developmental delay.…”

Encouraging postnatal cytomegalovirus (CMV) screening: the time is NOW for universal screening!

“…At the same time, Boppana et al [7] showed that CMV screening using saliva swabs had excellent sensitivity of 97.4-100% and specificity of 99.9%. Other investigators have utilized urine and umbilical cords for congenital CMV screening with some success [8,9], but the ease of collection of saliva swabs makes this method the currently preferred one for routine newborn screening [10]. A positive CMV saliva screen should be confirmed with a urine CMV PCR test or culture, as collection of saliva after breastfeeding could detect contamination from CMV present in breast milk rather than actual infection [11].…”