Universal screening for congenital cytomegalovirus (CMV) in newborns, using dried blood spot analysis during the first week of life, created opportunities to intervene for improved outcomes, a diagnostic study has shown.

Congenital CMV is the most common nongenetic cause of hearing loss in children and a leading cause of other neurologic disabilities. Without universal screening, infants who are asymptomatic for the virus are especially at risk for congenital CMV-related sequelae later in life, claimed the study’s authors in JAMA Network Open.

The burden of CMV disease in newborns is substantial, and efforts to prevent, diagnose, and treat CMV infection are of public health importance, wrote Norma P. Tavakoli, PhD, a virologist at the Wadsworth Center in Albany, New York, and her colleagues. Previously, screening only according to symptoms of congenital CMV led to missing more than half of all newborns who in fact had the virus, said Tavakoli and colleagues.

“[A]lthough clinicians frequently reported that symptomatic newborns were not recognized until after receiving a positive [congenital] cCMV screen, the knowledge of having a positive screen may have heightened scrutiny and increased identification of minor abnormalities,” they wrote.

To show the feasibility, screen-positive rate, and parental acceptance of newborn screening for congenital CMV using dried blood spots, Tavakoli and her co-investigators studied 208,322 blood specimens collected from newborns delivered in New York state between October 2, 2023, and September 30, 2024, to determine whether the virus was present. The specimens were collected as part of the state’s Newborn Screening Program. (Not all states screen for CMV.)

Parents were given the option to opt out of receiving CMV results. Newborns referred for follow-up were seen by infectious disease specialists at designated medical centers.

Of the 208,322 newborns whose specimens were collected, parents of 245 (0.1%) infants did not permit the CMV screen, which was conducted using polymerase chain reaction analysis. Another 22 families opted out of follow-up after the results were released. Still, the authors wrote, “This was the first time our program used an opt-out model for a pilot study. Opt-in models are labor intensive and expensive and may prevent some families from benefiting from additional screening for their newborn.”

Just over half the infants were boys (51%). The mean age at specimen collection was 1 day. Of those with results reported, 529 had positive CMV screen results (0.3%). After referral and initial diagnostic evaluation, 276 of the 529 newborns (52.2%) were given a congenital CMV diagnosis (overall rate of 0.1%). Among these, 68 (24.6%) had symptomatic congenital CMV disease, 197 (71.4%) had asymptomatic infection, and 11 (4.0%) had isolated sensorineural hearing loss.

Likely postnatal CMV infection occurred in 131 (24.8%) of the 529 referred newborns. False-positive screen results were found in 17 (3.2%) while 43 (8.1%) had unknown CMV classification. There were 62 (11.7%) infants lost to follow-up. In the 68 newborns with symptomatic congenital CMV disease, 48 (70.6%) were treated with antiviral medication.

Although the investigators’ intent was to detect congenital CMV, they identified some cases in which the CMV infections were postnatally acquired. “In general, postnatal infections do lead to different outcomes than [congenital] cCMV cases,” said Tavakoli. “Healthy, term newborns may have mild or no symptoms if they acquire CMV, although postnatal acquisition of CMV can cause symptoms that may warrant treatment in low birth weight/preterm infants.”

In an accompanying editorial, Pablo J. Sánchez, MD, professor of pediatrics at The Ohio State University (OSU) in Columbus, commended the spirit of the study, writing, “most preterm and some full-term newborns in the neonatal intensive care unit do not have a hearing screen performed before age 21 days, the critical period for diagnosis of congenital CMV infection. In addition, such a targeted strategy fails to identify as many as 43% of congenitally infected neonates who develop late-onset sensorineural hearing loss and subsequent neurodevelopmental disability.”

Sanchez said that saliva testing of newborns would be optimal. “A saliva sample obtained with a flocked or polyester swab placed in a liquid medium (eg, viral transport media) should be adapted for large-scale universal screening of newborns as it is easily obtained and has high sensitivity,” he wrote. Sanchez is also the principal investigator at the Center for Perinatal Research at the Abigail Wexner Research Institute , also at OSU.

Given the prevalence of congenital CMV infection, its associated sequelae, the availability of antiviral and supportive treatments, and targeted interventions for hearing impairment, efforts to advance universal screening should be prioritized, said Sanchez.

Tavakoli agreed that perhaps in the future, a saliva test for infants might be developed, but for the time being, “Newborn screening programs are set up to screen dried blood spots. This is the specimen type that is routinely used for all our screening tests.” Systems are in place in hospitals and other providers to collect and ship dried blood spots; then newborn screening programs accession, screen, and store the dried blood spots, she said.

“Until other systems are in place to collect, ship, test, and store other specimen types, it would be extremely difficult for newborn screening programs to test other specimen types.”

Tavakoli reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) during the conduct of the study. Sanchez reported receiving consulting fees from Merck, Sharp & Dohme and Kamada outside the submitted work. No other disclosures were reported.