Congenital CMV Testing Paves the Way for Early Intervention and Healthier Outcomes

While human cytomegalovirus (CMV) infection is often asymptomatic for babies—particularly newborns or developing fetuses—this infection can cause severe health outcomes. CMV may pass to babies in utero and may result in congenital CMV (cCMV). cCMV is a leading cause of hearing loss, as well as lifelong neurodevelopmental issues such as microcephaly and seizures. Alarmingly, one in five babies infected with cCMV will have long-term health problems, making diagnosis and prompt disease management key to better outcomes.¹

Early intervention with antiviral treatments can make a significant difference for newborns, alleviating some symptoms and allowing for increased quality of life. Such interventions are only possible with an accurate and timely diagnosis. Unfortunately, diagnosing cCMV can be challenging.

The key to diagnosing cCMV

First and foremost, the key to diagnosing cCMV in babies is knowing that diagnosis is needed. Some 90 percent of babies born with cCMV appear to be completely healthy. In the small fraction of cases where symptoms are present, they tend to be nonspecific. Of the 30,000 babies born with CMV annually in the US, only 1 percent are diagnosed based on clinical signs.

Another critical factor needed to diagnose cCMV is correct timing. cCMV must be detected from a sample within the first three weeks of the newborn’s life to determine that the infection is congenital, since treatment routines differ for babies who contract CMV after birth.

The only way to comprehensively detect cCMV cases is to include this infection within a standard newborn screening panel. In 2019, the National CMV Foundation formally requested that cCMV be added to the Recommended Uniform Screening Panel. This protocol offers the only federal recommendations for newborn screening and is used by many states as the basis of their own universal screening programs.² While progress on this front in the US has proved slow, it has been persistent and measurable. Just last year, Minnesota became the first state to add cCMV to its universal newborn screening guidelines. Further, numerous other states are now considering similar measures.

cCMV screening across the US

Until cCMV screening is broadly enacted across the US, families will be subjected to the newborn diagnostic screening protocols within their state. While Minnesota is currently the only state to screen all newborns for cCMV, 19 other states offer some kind of targeted cCMV testing, and 24 states have implemented some form of legislation, education, or screening related to cCMV.

A number of institutions across the country have begun screening smaller, high-risk populations of babies, like those who have been admitted into the neonatal intensive care unit. Many algorithms determine that cCMV testing is required for newborns who fail their hearing screening. However, these standard hearing tests may produce inaccurate results. In addition, babies born with cCMV may successfully pass their hearing screenings but lose their hearing later in life.

In light of broader cCMV screening and the substantial health benefits achieved through early detection and intervention, clinical laboratories should consider incorporating molecular testing designed for cCMV detection. Clear testing guidance from the Centers for Disease Control and Prevention (CDC) can be helpful in establishing algorithms for molecular diagnosis of cCMV.

Molecular testing is ideal for cCMV diagnosis

The ability to test for cCMV has been greatly improved through the use of molecular diagnostics. These tests offer highly sensitive detection and notably faster results compared to conventional testing options such as viral culture.

According to the CDC, PCR-based testing is currently considered to be the gold standard for diagnosing cCMV in newborns.³ The CDC recommends testing a saliva sample obtained within the first three weeks of life, collected at least one hour after breastfeeding. If the saliva sample is positive, the CDC advises collecting a urine sample to confirm. Dried blood spot samples, while theoretically ideal for newborn testing, have not proven to deliver the sensitivity needed to avoid false negative results. However, dried blood spots may add value if they baby is not tested within the first three weeks and is later suspected as having cCMV.

Molecular tests are able to provide optimal sensitivity from saliva and urine samples, and typically deliver results within hours to support early treatment intervention when needed.

In light of the newly issued rule governing laboratory-developed tests from the U.S. Food and Drug Administration (FDA), clinical labs looking to implement cCMV testing may find a commercially available, FDA-cleared, PCR-based test a more convenient option than designing their own custom assay.⁴

PCR-based tests offer ease of use with sample-to-answer systems that handle sample processing, testing, and data generation without manual intervention. To comply with CDC guidelines, ideally, the test chosen should be FDA cleared to run urine samples as well as saliva samples.

Rapid laboratory molecular cCMV diagnostic tests have made it possible to generate reliable results in a clinically actionable timeframe for vulnerable babies. With broader screening for cCMV under consideration in an increasing number of states, it is an ideal time for clinical laboratories to review their neonatal testing needs and consider the implementation of cCMV testing to make an impact on this dangerous disease.

References:

CDC. Cytomegalovirus (CMV) and Congenital CMV Infection: About Cytomegalovirus. Updated: May 30, 2024. https://www.cdc.gov/cmv/index.html
Health Resources & Services Administration. Recommended Uniform Screening Panel. Updated: August 2023. https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp
CDC. Cytomegalovirus (CMV) and Congenital CMV Infection: Laboratory Testing for CMV and Congenital CMV. Updated April 15, 2024. https://www.cdc.gov/cytomegalovirus/php/laboratories/?CDC_AAref_Val=https://www.cdc.gov/cmv/clinical/lab-tests.html
U.S. Food & Drug Administration. FDA Takes Action Aimed at Helping to Ensure the Safety and Effectiveness of Laboratory Developed Tests. April 29, 2024. https://www.fda.gov/news-events/press-announcements/fda-takes-action-aimed-helping-ensure-safety-and-effectiveness-laboratory-developed-tests