Federal data indicate that over half the US population aged 6-46 years is infected with cytomegalovirus (CMV), typically spread through bodily fluids. Most people have mild or no negative effects from the infection.

But fetuses that are infected with the virus from their mother are at a risk for birth defects ranging from brain damage to stillbirth and immunosuppressed patients can suffer deadly effects.

Awareness in the US population of CMV’s status as the leading cause of birth defects is notably low, even in the medical world. A study published in 2020 found that only about half of the obstetricians discuss the virus with their patients, despite CMV being the most common congenital infection. CMV infection occurs in 2.2% of all neonates, according to the CDC.

The same study found that younger physicians tended to be more familiar with the deleterious outcomes of CMV infection than older ones and that educational interventions were effective in equalizing their knowledge.

Epidemiology

Eighty percent of CMV infections of the fetus occur in the first trimester, according to Mark Schleiss, MD, a professor of pediatric infectious diseases at the University of Minnesota (UMN), Minneapolis. It is in the first trimester when there is the most potential for brain damage because of the fetus’s lack of an immune system, he said in an interview, which allows the infection to interfere with neural migration.

“These babies are born with severe brain injuries, and then there is the stuff going on with the cochlea, so they are born deaf with a small, misshapen brain,” Schleiss said.

He is currently studying what happens to the fetus when infected in the second and third trimesters, which, so far, seems to lead to less severe injury.

Schleiss said that the fear of causing distress keeps some obstetricians from discussing CMV with their pregnant patients. The American College of Obstetricians & Gynecologists does not take a position on whether newborns should be screened, noting that the effect is still being evaluated, although some states already require it.

“If you have a normal, happy baby, but then the state comes back with a report that says your baby has CMV, the worry is that you’re maybe doing harm. I reject that. It’s paternalism. I give the families the information and help them work through it. And focus groups show moms would rather know,” he said.

To date, public health initiatives to combat CMV have been weak, but Congress has recently taken an interest in quelling the virus. Late in 2025, a bill was put forth in Congress to require states to screen all newborns for CMV.

“There is bipartisan support for this on Capitol Hill,” said Sallie Permar, MD, PhD in an interview with Medscape Medical News. “The bill is to promote the awareness and testing by the CDC for all newborns, because we have evidence of that being a cost-effective strategy to minimize CMV impact. It also calls for more research at the NIH for prevention and treatment,” Permar said.

Permar, chair of the Department of Pediatrics at Weill Cornell Medicine in New York City, where she is a professor of pediatrics and a professor of immunology and microbial pathogenesis, is among those leading the charge to raise awareness about CMV. “The virus can cause epilepsy, liver damage, and also, it has been associated with a higher risk for childhood leukemia,” she said.

If the Stop CMV Act now in Congress becomes law, then states will have 2 years after its passage to implement their own screening programs, or use the one set out federally. Minnesota and Connecticut currently require universal congenital CMV screening for all newborns. Many other states, including New York, Florida, and Texas, have mandated targeted screening for infants who fail their initial newborn hearing test.

Attempts at a Vaccine

At the turn of this century, the Institute of Medicine (now National Academy of Sciences, Engineering and Medicine) prioritized CMV as a public health target for the 21st century, saying that developing a CMV vaccine was among the highest priorities in its assessment of targets for vaccine development.

In late 2025, a highly anticipated phase 3 clinical trial of an mRNA vaccine for congenital CMV was scrapped after the study went wide of its efficacy end points. “It was a huge disappointment because it got further than any other vaccine,” Permar said.

The clinical trial data are as yet unpublished, but a media advisory claims the efficacy results in healthy women reached between 6% and 23%, depending on the criteria applied. The target endpoint was prevention of CMV infection in seronegative women of childbearing age. The trial was conducted across 300 multinational sites, with 7454 women (16-40 years of age) randomized to the study arm or placebo, in the observer-blind, phase 3 trial (NCT05085366).

Were a CMV vaccine ever to come to market, Schleiss said every woman of childbearing age should receive it. “The goal of the vaccination is to protect the moms from ever getting a CMV infection in the first place,” Schleiss said.

Currently, there are 102 ongoing trials of CMV therapies, including for prevention, with only 14 at the phase 2-3 or phase 3 level, according to an industry news report.

Transplant Patients Also at Risk

Typically, there are no symptoms during the initial CMV infection, although the virus can sometimes present as a mild flu before establishing lifelong latency, according to Schleiss. However, CMV can be reactivated and possibly turn deadly in patients who are severely immunosuppressed, such as transplant patients.

Transplant patients recently were found to have high mortality rates due to pneumonia caused by CMV infection. In a study published in 2025, at 1 month after transplant the CMV respiratory infection mortality rate was 21.6%. At 1 year, that rate was 51.4%, and at the 5-year mark, the rate was 69.2%.

There have also been attempts to create a vaccine for this patient population, but Kevin Downes, MD, an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, Philadelphia, wonders if the transplant community is large enough to justify the investment. “Certainly, transplant patients make up the majority of patients who get CMV [respiratory disease], especially pediatric transplant patients,” said Downes, the lead author of a paper on managing CMV in pediatric organ transplant patients.

If a vaccine for transplant patients were to be achieved, however, Downes said it would be helpful. “If you give someone a CMV vaccine prior to their transplant, and they mount an immune response to it, even if it doesn’t prevent the transmission of CMV with the organ transplant, it prevents them from getting sick.”

However, CMV is treated in affected patient populations, Permar said that doctors and others in the medical profession should keep talking about it. “Keep promoting the need for research, let’s get that to fruition, get the dollars necessary for appropriation to where CMV research is needed.”

Downes reported being site primary investigator for a multicenter clinical trial sponsored by Merck, Inc (this is a trial of an antiviral for CMV prevention in pediatric solid organ transplant) and for an investigator-initiated study sponsored by Veloxis Pharmaceuticals (this is a study involving pediatric solid organ transplant but is unrelated to CMV). Schleiss reported being the site principal investigator for the Moderna mRNA-1647 study but all funds go to UMN. Permar reported providing individual consulting services to Moderna, Merck, Dynavax, Pfizer, Kamada, and Imunon (for vaccines). Dynavax, Kamada, Pfizer, and Moderna have provided grants for her Institutional sponsored program; amount received was noted < $5000.