Coming Out Screening

Cytomegalovirus (CMV) is a common cause of infection in humans, but it’s not typically a cause for concern. In fact, experts estimate that half of US adults become infected with CMV by the time they reach 40 years old (1), but adult infections tend to be mild – often unnoticeable – and the virus then usually becomes dormant. However, CMV infection in a newborn is far more serious.

CMV is the most common infectious cause of congenital defects in the United States. About one in every 200 babies is born with congenital CMV (2). CMV can be transmitted from mother to baby during pregnancy or postnatally. Although cases of congenital CMV can be deadly or have lifelong neurodevelopmental impacts, infections acquired after birth have less severe outcomes. Unfortunately, early detection for congenital infection is challenging; almost all babies born with CMV appear healthy, but one in five are at risk of dying from infection-related complications. Those who survive are more likely than their healthy counterparts to suffer from hearing loss or developmental delays later in life.

Universal newborn screening for CMV infection would help identify patients in need of antiviral treatment, but CMV is not currently included in US federal screening guidelines. Universal newborn hearing screening is in place (as recommended by the American Academy of Pediatrics), but many infected newborns pass the initial hearing test only to later exhibit hearing loss due to undetected CMV infection. Some states do offer CMV screening for newborns that fail the hearing test, but the recommendations and approaches vary significantly by geography. So far, Minnesota is the only state to pass legislation requiring CMV screening for all newborns. The Vivian Act was passed by the Minnesota state legislature in July 2021 – adding congenital CMV to the Minnesota newborn screening panel.

Clearly, there is a pressing need to improve newborn CMV testing to detect cases as early as possible. Identifying that CMV infection was acquired before birth must be done before the baby is approximately one month old. After that time, newborns can be infected via other exposures after birth where the consequences of infection are much less severe. Treatment in the first month of life with medications such as valganciclovir or ganciclovir can improve a baby’s health outcome, mitigating future hearing loss or developmental delays (3,4).

What type of testing is best? Molecular testing could offer notable improvement over less sensitive test methods (such as viral culture) that can take weeks to complete, giving healthcare professionals a better chance at detecting congenital CMV early enough to make a significant difference. PCR tests – the most robust molecular diagnostic technology – can be deployed with either saliva swabs or urine samples, which are currently recommended by the CDC for diagnosing and confirming congenital CMV in newborns (5). Developers of rapid, easy-to-use molecular diagnostics are also making strides toward commercially available CMV assays that would generate highly accurate results with both sample types.

The sample-to-answer approach
 

Though there are many types of molecular diagnostic tests, one approach may hold great potential for moving toward universal CMV screening in newborns using saliva swab specimens. Sample-to-answer systems are molecular test platforms in which all steps, including most sample preparation and processing, are performed automatically. Users simply load the sample and ready-to-use reagents into a consumable or cartridge, insert it into the testing instrument, and press start.

These systems offer a number of benefits – their automated approach typically leads to rapid results (sometimes in as little as one hour) and, because they require minimal training, they are easier for clinical lab teams to install, validate, and run. For clinical labs with limited bench space, these flexible systems can be a good way to maintain a broad test menu without adding lots of new equipment. 

Adopting a sample-to-answer approach would enable labs to expand their CMV testing capabilities rather than being limited to relying on those facilities with sufficient resources to develop and validate a PCR-based laboratory-developed test. Because these platforms are offered by commercial diagnostic developers, the assays are typically cleared by the FDA as in vitro diagnostic assays, minimizing the validation required for clinical laboratory use.

As recognition of the challenges associated with congenital CMV detection increases, more diagnostic manufacturers are developing molecular tests for newborns. As the utility and accuracy of these assays are confirmed in clinical studies, commercial test availability may finally bring CMV screening to more babies – perhaps even to all newborns if CMV can be incorporated into universal screening recommendations. This would represent a huge step forward in providing early interventions for better outcomes in one of our most vulnerable populations.