Research Update - Universal CMV Screening

Research Update - Universal CMV Screening

Two recent studies, “Outcomes of a Population-Based Congenital Cytomegalovirus
Screening Program” published in JAMA Pediatrics and “Universal Screening for
Congenital Cytomegalovirus Infection” in JAMA Network Open, add compelling
evidence supporting the necessity and feasibility of universal screening for congenital
cytomegalovirus (cCMV). Together, these studies show that population-based screening
programs can be successfully implemented and identify a substantial number of infants
with cCMV who would not be detected through current clinical or targeted approaches.
They also demonstrate that early identification enables timely evaluation, structured
follow-up, and access to antiviral therapy when indicated.

Congenital cytomegalovirus remains a leading infectious cause of sensorineural hearing
loss and a significant contributor to neurodevelopmental disability in children. A key
challenge in its management is that most affected infants are asymptomatic at birth, and
both hearing loss and developmental sequelae may not develop for months or,
sometimes, years. As a result, reliance on symptom-based identification or targeted
testing has historically led to delayed recognition and underdiagnosis.
Across both studies, a substantial proportion of infants identified through screening
were asymptomatic at birth. Further, even among infants who were ultimately classified
as symptomatic, many were not recognized as having cCMV until screening results
established the diagnosis. These findings reinforce that clinical presentation alone is not
an effective strategy to reliably identify affected newborns, thus underscoring the
importance of universal screening.

The studies also demonstrate that cCMV screening can be integrated at a population
level into existing newborn screening systems. When appropriate education was
provided, screening programs achieved high uptake and very low opt-out rates, while
prior evidence suggests that over 90% of parents of children with cCMV were unaware
of the virus before diagnosis. Following identification through screening, infants were
enrolled in structured follow-up pathways that included audiologic monitoring,
developmental surveillance, and referral to specialist care when indicated.
Despite demonstrating feasibility and efficacy within existing newborn screening
systems, both studies highlight important limitations of dried blood spot (DBS) testing.
Although DBS allows integration into routine screening infrastructure and improves case
detection compared with current clinical or targeted approaches, it has consistently
shown suboptimal sensitivity, with meta-analytic estimates suggesting a pooled
detection rate of 62.3%. In both programs, a meaningful proportion of infants with
confirmed cCMV were not identified through DBS screening, and both false-positive and

false-negative results were observed. These findings reinforce the need for confirmatory
diagnostic testing using established standards such as urine PCR.
Both studies conclude that DBS alone is not an optimal screening strategy. The Ontario
population-based screening study (Outcomes of a Population-Based Congenital
Cytomegalovirus Screening Program) supports further evaluation of both urine and
saliva as potential primary screening specimens to improve detection. The
accompanying JAMA Network Open commentary (Universal Screening for Congenital
Cytomegalovirus Infection) takes a more definitive position, identifying saliva as the
preferred specimen for universal newborn screening based on its higher sensitivity and
ease of collection.

Taken together, these findings suggest that while DBS-based screening is a feasible
and effective entry point for population-based programs, it is not sufficient as a stand-
alone strategy for identifying all cases of cCMV. They also support higher-sensitivity
specimens for primary screening, particularly saliva, while also supporting further
evaluation of urine.

Despite current limitations, early identification through DBS screening was associated
with meaningful clinical benefits. Infants diagnosed through newborn screening were
able to receive earlier and more structured follow-up, including hearing surveillance and
developmental monitoring during critical periods of language acquisition. Among
symptomatic infants, some received antiviral therapy with valganciclovir following
clinical evaluation. Importantly, many infants would have remained undiagnosed without
universal screening.

These findings support universal newborn screening for cCMV as both feasible and
clinically impactful. DBS-based screening improves case detection compared with
current clinical or targeted approaches, although alternative strategies may be more
effective. Given the burden of disease and the demonstrated benefits of earlier
identification, these findings add further evidence supporting the need for universal
newborn cCMV screening.

Dunn JKE, Chakraborty P, Reuvers E, et al. Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program. JAMA Pediatrics. 2025;179(3):332-339. doi:10.1001/jamapediatrics.2024.5562

Tavakoli NP, Sack V, Handel AS, Giacinto A, Pearce M, Ojukwu I, McManaman C, St-Pierre M, DiAntonio L, Saavedra-Matiz C, Brandon CJ. Universal newborn screening for congenital cytomegalovirus using dried blood spot specimens. JAMA Network Open. 2026 Jan 29;9(1):e2554518.