BOSTON — The time for universal congenital cytomegalovirus (cCMV) screening may well be here, researchers said.
In a study of nearly 24,000 newborns across six hospitals in Minnesota, testing for cCMV using a dried blood spot sample found a prevalence of 3.7 cases per 1,000 births, reported Mark R. Schleiss, MD, of the University of Minnesota in Minneapolis, during his late-breaking abstract presentation at the IDWeek annual meeting.
The controversial practice has been debated for years, as parents and healthcare providers continue to express concerns about overtreating infants who screen positive, but are asymptomatic, with powerful, expensive antivirals, especially since federal guidelines still don’t call for newborn CMV screening.
However, early CMV screening gives parents and clinicians a heads-up that hearing might be compromised either at birth or may become compromised as the baby grows, said Schleiss.
“Although most of these babies do very well, we have a subset who will go on to have hearing loss, even if they have normal hearing at birth,” he explained. “That makes newborn screening for CMV very different than the plethora of diseases that we test for in infants, virtually all of which have bad outcomes unless they’re caught very early in life.”
“CMV generally has a good outcome in most infants, but some of the problems can be missed,” he added. “Having some anticipatory guidance for those babies, including otological and neurodevelopmental follow-up, can be very vital.”
In an initial analysis by Schleiss and colleagues, the clinical sensitivity of dried blood spot testing was 73.2% at the University of Minnesota and 76.8% at the CDC, while the saliva polymerase chain reaction (PCR) test had a sensitivity of 93%.
However, dried blood spot samples are already obtained from every newborn and used to test for multiple genetic and metabolic disorders, making this testing convenient and cost-effective. Saliva PCR testing also carries a higher false-positive rate, Schleiss noted. “There is the risk of having false-positive tests with saliva because of CMV DNA that appears in breast milk.”
Among the 21 infants in the current study who were symptomatic at birth and/or developed sensorineural hearing loss (SNHL), the clinical sensitivity of saliva PCR was 95%; for dried blood spot testing, it was 75% at the University of Minnesota and 85% at the CDC.
“We would argue to critics of universal general screening that when we consider the clinical sensitivity of dried blood spot testing, the blood spot has value in predicting the infants who are at risk for some sequelae,” Schleiss said. “So, are we there yet? Are we ready to say, okay, let’s do this? Well, moms are voting with their feet. They’re going down to state legislatures to try to pass bills to codify universal screening.”
Universal newborn CMV screening has been the law in Minnesota since 2021. Other states are paying attention, Schleiss noted. Connecticut has passed legislation calling for universal newborn CMV screening to start in 2025. In September, the New York State Department of Health announced that cCMV will be added to its newborn screening panel. The free testing will be conducted during routine newborn screening.
“Several provinces in Canada already do this, so this is a very exciting time,” Schleiss said. “But we need more data and more knowledge, and we do need to come to terms with the fact that even though universal screening has now become practice in some states and provinces, the newborn screening community has not really endorsed this yet. So that will be an interesting discussion in the years ahead.”
Out of 23,644 newborns screened, 87 were identified as having cCMV, of whom 78% were asymptomatic at birth.
Infants who screened positive had a confirmatory urine PCR test and a diagnostic clinical evaluation. Schleiss and team used international consensus criteria to categorize cases as moderate-to-severe, mildly symptomatic, asymptomatic with isolated sensorineural hearing loss, or asymptomatic.
In this cohort, six infants were moderately-to-severely symptomatic, including two with SNHL. Nine newborns were mildly symptomatic, and four were asymptomatic with isolated SNHL.
Four developed delayed-onset SNHL; two were asymptomatic at birth and two were symptomatic. Among the 21 who were symptomatic or developed later-onset hearing loss, 18 were treated with valganciclovir (Valcyte).
“In total, 10 of 87 infants to date have demonstrated variable degrees of SNHL,” Schleiss said. “That amounts to 11.5% of these infants.”
Schleiss reported receiving funding from the CDC, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina’s Disability Research and Dissemination Center.
Source Reference: Schleiss MR, et al “Universal newborn screening for congenital cytomegalovirus (cCMV) comes of age: clinical sensitivity of screening tests and infant outcomes in a cCMV screening study in Minnesota” IDWeek 2023.