Universal newborn screening for congenital cytomegalovirus infection

Abstract

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of childhood disability, in particular sensorineural hearing loss (SNHL). Timeliness of diagnosis is crucial, since the presence of CMV in any compartment (eg, blood, urine, or saliva) after age 21 days can mean postnatal acquisition of infection, particularly in breastfed infants. Given these issues, there is considerable interest in implementation of screening programmes—either universal screening (where all newborns are tested) or targeted screening. Targeted screening is typically based on the outcome of a newborn hearing screen, and can be influenced in some strategies by findings of other signs suggestive of congenital CMV. Universal screening is likely to have the greatest overall benefit. Early identification of congenital CMV allows for interventions such as antiviral therapy (when indicated) and enables anticipatory audiological monitoring that facilitates timely detection of delayed-onset SNHL. However, there are debates about the effectiveness of screening programmes. Most infants with congenital CMV are unaffected and do not appear to be at risk for adverse neurodevelopment outcomes, except for SNHL. Screening can, therefore, raise unwarranted concern among parents and clinicians in these cases. The best clinical sample for diagnostic testing is unclear. PCR testing of saliva is sensitive but has a risk of yielding false-positive results in infants without congenital CMV. Resolving the technological issues has improved the sensitivity of dried blood spot (DBS) PCR but the technique remains suboptimum. An advantage to DBS PCR testing is that an infrastructure exists to add this test to existing newborn screening programmes. In this Review, the advantages and disadvantages of congenital CMV screening are discussed, along with high-priority areas for future research that will inform and direct this rapidly evolving field.