A large three-year newborn screening program found that more than half of babies with congenital CMV would have been missed by standard targeted screening because many appeared healthy at birth. The findings suggest that routine saliva-based screening could help identify affected infants earlier, allowing for closer monitoring and, when needed, timely treatment, while pooled testing may make large-scale screening more practical.
A newborn can look perfectly healthy, pass a hearing test and still carry an infection that may affect hearing or development later in childhood. That is the challenge posed by congenital cytomegalovirus, or cCMV, one of the most common infections passed from a mother to a baby during pregnancy. Most babies born with the virus show no obvious signs at birth, making it difficult to know which children may need closer monitoring.
Now, a large three-year study led by Prof Dana Wolf of the Hadassah Medical Center and the Hebrew University of Jerusalem, Prof Smadar Eventov Friedman of the Hadassah Medical Center, and Prof Moran Yassour of the Hebrew University of Jerusalem suggests that routinely screening all newborns could uncover many of these otherwise invisible cases. The study was published in The Lancet Infectious Diseases.
The researchers reported on the screening of 48,556 newborns, representing nearly 95 percent of babies born at two hospitals of the Hadassah Medical Center in Jerusalem between April 2022 and March 2025. They identified 176 infants with congenital CMV, or about 3.6 cases for every 1,000 babies screened.
The most striking finding was how many would otherwise have gone undetected.
Under the more common targeted approach, babies are generally tested when there is a reason to suspect CMV, such as a failed hearing test, signs of congenital CMV illness or a known maternal infection during pregnancy. But 100 of the 176 babies with cCMV, or 57 percent, would not have qualified for this type of screening.
In other words, more than half appeared healthy enough that there would have been no obvious reason to test them.
That matters because congenital CMV is a leading cause of non-genetic hearing loss and can also affect neurological development. Some complications may only emerge later. Early diagnosis can allow doctors to monitor hearing and development and, in certain cases, begin antiviral treatment during a time-sensitive window.
Among the 100 babies who would have been missed without universal screening, eight were later found to have moderate to severe signs of cCMV, while three had hearing loss despite appearing otherwise asymptomatic. Eleven ultimately received antiviral treatment.
Making universal screening practical
Testing every newborn individually could place a significant burden on hospital laboratories. The pooled-testing approach builds on a method the team originally developed to increase the number of COVID-19 PCR tests that laboratories could process during the pandemic. They have now adapted that same strategy for a very different, ongoing public health challenge: screening newborns for congenital CMV. The researchers therefore used a pooled saliva-testing system.
Saliva samples from several babies were combined and tested together using PCR. If a pooled sample tested positive, the babies were investigated further, with positive saliva results confirmed through urine testing.
This approach reduced the number of laboratory tests required by 83 percent compared with testing each sample separately, while maintaining a high sensitivity of detection and allowing nearly 95 percent of newborns to be screened.
Passing the hearing test does not rule out CMV
Newborn hearing tests remain important, but the findings show that they cannot catch every baby affected by CMV.
Some babies discovered only through universal screening had sensorineural hearing loss despite passing the routine newborn hearing test. At one year, a small proportion of babies detected only through universal screening had permanent hearing or balance-related problems.
There was also reassuring news. Among babies found only through universal screening who were completely asymptomatic after their initial medical evaluation, those with one-year follow-up had normal hearing and development. The researchers cautioned, however, that some effects can appear later, making longer-term follow-up important.
Previous CMV infection does not eliminate the risk
The study also found that congenital CMV was not limited to mothers experiencing their first infection.
Among 158 cases where the mother’s infection history was known, 53 percent followed a non-primary infection, meaning the mother had previously been exposed to CMV, while 47 percent followed a first infection. Babies in both groups had similar rates of significant symptoms, hearing loss and complications at one year.
Should every newborn be screened?
The researchers say their findings strengthen the case for universal newborn CMV screening and show that pooled saliva testing can make large-scale screening more practical.
Still, questions remain. The study was conducted at two hospitals, and researchers noted that screening can sometimes uncover findings whose medical significance is unclear. The study also did not directly assess the overall cost-benefit of universal screening, which the authors say should be examined before widespread implementation.
The central problem, however, is simple: many babies with congenital CMV look completely healthy at birth.
Without routine screening, some may only be identified after hearing or developmental problems begin to appear. Universal screening could give doctors and families the chance to find those children earlier.
Prof Dana Wolf (Credit- Dana Wolf)
Prof Moran Yassour (Credit – Ariel Van Straten)
Media Contacts
Prof Dana Wolf
Tel: +972 50-787-4235 Email: danaw@ekmd.huji.ac.il
Prof Moran Yassour
Tel: +972 54-995-9886 Email: Moran.Yassour@mail.huji.ac.il
Research Paper
Eventov Friedman, S., Ofek Shlomai, N., Oiknine-Djian, E., et al. “Lessons derived from a 3-year congenital cytomegalovirus screening programme in Israel: a prospective population-based cohort study.” The Lancet Infectious Diseases, 26 (2026), 384–393.
DOI: https://doi.org/10.1016/S1473-3099(25)00620-6
Authors:
Smadar Eventov Friedman ∙ Noa Ofek Shlomai∙ Esther Oiknine-Djian ∙ Tal Sido ∙ Oren Gordon ∙ Sraya Greenberger ∙ Hadar Horowitz ∙ Lior Merav ∙ Stav David Mehaber ∙ Orit Caplan ∙ Miriam Geal-Dor ∙ Natalia Simanovsky ∙ Diana Averbuch ∙ Colin Kunzweiler ∙ Yosefa Hefter ∙ John Diaz-Decaro ∙ Ora Paltiel ∙ Moran Yassour∙ Dana G Wolf
Affiliations:
- Department of Neonatology, Hadassah and Hebrew University Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
- Clinical Virology Unit, Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Hebrew University Faculty of Medicine, Jerusalem, Israel
- Lautenberg Center for General and Tumor Immunology, Jerusalem, Israel
- Pediatric Infectious Diseases, Pediatric Division, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- School of Computer Science and Engineering, Hebrew University of Jerusalem, Jerusalem, Israel
- Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
- Speech and Hearing Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Department of Communication Disorders, Jerusalem Multidisciplinary College, Jerusalem, Israel
- Pediatric Radiology Unit, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Moderna Therapeutics, Cambridge, MA, United States of America
- Medison Pharma, Petah Tikva, Israel
- Braun School of Public Health and Community Medicine, Hadassah Medical Organization, Jerusalem, Israel