A newborn tests positive for congenital cytomegalovirus (cCMV) infection, the most common congenital infection. The baby appears healthy, with no obvious neurologic or other signs of disease. Does the diagnosis alone warrant a referral to a pediatric ophthalmologist?

The question is becoming more pressing because more health systems screen newborns for cCMV, a leading cause of nongenetic sensorineural hearing loss.

A new population-based study in Canada suggests that CMV-related eye abnormalities are rare among infants identified through newborn screening, especially among those classified as asymptomatic. But an accompanying commentary warns that subtle signs of disease can be missed, making it difficult to determine which infants need further evaluation.

Researchers reviewed eye examination results for 347 infants who tested positive for cCMV between July 2019 and January 2022. Of these, 51 infants (14.7%) were ultimately classified as having symptomatic infection. Overall, 324 infants (93.4%) had normal eye examinations.

Only two infants had chorioretinal scars attributed to cCMV, representing 0.58% of all infants who screened positive and 3.9% of those with symptomatic infection. Both had significant signs of disease affecting other parts of the body and had been referred to ophthalmology before their screening results were available. No infants classified as asymptomatic had CMV-related eye findings.

The results raise questions about whether every infant who tests positive for cCMV needs a routine eye examination, particularly when specialist appointments can be difficult to access, according to study author Kamiar Mireskandari, PhD, John and Melinda Thompson Chair in Vision Research at The Hospital for Sick Children in Toronto, Ontario, Canada.

“Screening everyone is not required unless the infectious diseases team identifies them as symptomatic,” said Mireskandari.

He also questioned whether urgent referrals change how infants are being treated.

“We found that seeing an ophthalmologist urgently — many of the consults are sent in that way — did not alter management for these babies,” he said. Pediatric and infectious disease teams, he added, have time to assess whether an infant has symptomatic disease before an ophthalmology referral is made.

Defining ‘Asymptomatic’

The findings do not necessarily mean that baseline eye examinations should be abandoned, according to Gail J. Demmler-Harrison, MD, infectious disease specialist at Texas Children’s Hospital in Houston. In an accompanying commentary, she cautioned that identifying which infants are truly asymptomatic can be challenging.

“The classification of infants as asymptomatic at birth is inherently dependent on the quality, scope, and interpretation of the initial evaluations,” Demmler-Harrison said.

A newborn may appear well but have abnormalities on brain imaging or laboratory tests, an enlarged liver, spots on the skin called petechiae, or a low birth weight for gestational age, all of which signal CMV-related disease. Previous research has also documented eye lesions in some infants initially considered asymptomatic, as well as eye problems that emerge later in childhood.

A baseline examination can also reassure families and establish a relationship with an ophthalmologist should problems develop later, Demmler-Harrison added.

Dennis Kuo, MD, chief of the Division of Developmental and Behavioral Pediatrics at the Golisano Children’s Hospital at the University of Rochester Medicine in Rochester, New York, and a co-author of the American Academy of Pediatrics (AAP) clinical report on cCMV, emphasized the need to distinguish a positive test from evidence of disease.

The AAP report recommends ophthalmologic evaluation for infants with signs of CMV disease. Infants with cCMV and isolated sensorineural hearing loss also warrant ongoing evaluation. By contrast, a positive cCMV screening result alone does not automatically mean that an infant needs an urgent ophthalmology referral.

For infants who appear asymptomatic, routine pediatric care remains important.

“In the context of primary care, you’re always doing some level of eye exams,” Kuo said.

“We’re looking for changes in visual fixation,” he said, adding that pediatricians should look for “misalignment” of the eyes and “loss of red reflex” or other signs of changes in vision.

Kuo noted that the AAP report is also intended to help clinicians prioritize children who are most likely to need additional evaluation while recognizing that access to specialty care varies.

“Early identification is critical for optimal child development, and we really should be looking at expanding equitable access to screening, diagnosis, and follow-up care,” said Kuo.

Hearing Follow-Up Remains Essential

Although the need for routine eye examinations remains open to debate, experts emphasized that hearing surveillance is essential for all infants with cCMV. Some develop hearing loss after birth even when their initial hearing evaluation is normal, which is why the AAP recommends ongoing monitoring.

State Early Hearing Detection and Intervention programs can help connect infants with diagnostic testing and treatment, although access varies by location, said Kuo.

“The goal is to prevent families from getting lost between newborn screening, diagnostic evaluation, and early intervention,” he said.

The practical message for clinicians, according to Kuo, is to treat a positive cCMV screen as the start of an evaluation, not as a complete assessment of the infant’s risk. The child’s examination, laboratory results, imaging, hearing status, and other clinical findings should guide referrals and follow-up.

“If you are really concerned because you know the combination of additional risk factors, then those are the ones you really have to prioritize,” Kuo said.

Demmler-Harrison and Kuo reported having no relevant conflicts of interest. Mireskandari reported being a consultant for Bayer.

Lara Salahi is a health journalist based in Boston.