Science Update: Scientists develop noninvasive method to predict congenital CMV infection

A healthcare provider wearing a white coat holds the hand of a pregnant person while talking with her.
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Researchers have developed a calculator external link to estimate the risk that cytomegalovirus (CMV) infection will pass to a fetus during pregnancy. This congenital CMV infection occurs in about 20% to 40% of cases of primary maternal CMV infection. By offering a noninvasive way to predict the chance of congenital CMV based on individual characteristics, the calculator may help healthcare providers counsel pregnant people with CMV.

The work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health. It was led by Dwight J. Rouse, M.D., of Women & Infants Hospital of Rhode Island. Development and validation of the method are described in Obstetrics & Gynecology.

Background

Approximately five out of every 1,000 infants in the United States are born with CMV. Although most babies with congenital CMV do not develop long-term health problems, the infection can cause hearing loss and other neurologic effects that can lead to lifelong disabilities. Ultrasound may reveal some effects of congenital CMV infection, such as changes in brain structure, but most fetuses with CMV do not show any signs of infection on ultrasound.

Researchers set out to develop and validate a noninvasive method to predict the likelihood of congenital CMV infection when a pregnant person has primary CMV infection, but ultrasound does not suggest fetal infection. They analyzed data collected during an NIH-funded clinical trial assessing a potential therapy to prevent congenital CMV infection. The trial, conducted by NICHD’s Maternal-Fetal Medicine Units (MFMU) Network, established that infusions of CMV hyperimmune globulin early in pregnancy did not decrease the likelihood of congenital CMV infection.

Results

The researchers analyzed data from 344 clinical trial participants, of whom 68 delivered babies with CMV, to identify factors that predict individual risk for congenital CMV. They found that combining four variables— three blood test measurements and the type of medical insurance held by the pregnant person—produced the best estimates of congenital CMV risk. Congenital CMV infection was more likely if the pregnant person had high levels of IgM antibody against CMV, low CMV IgG avidity (a measure that helps distinguish a recent CMV infection from an older one), detectable levels of the virus in blood, and government-assisted health insurance. Depending on these individual characteristics, the predicted risk of congenital infection varied from 3% to 69%.

Significance

Personalized estimates of risk for congenital CMV infection can help pregnant people and their healthcare providers make decisions about whether to undergo invasive testing such as amniocentesis to detect fetal CMV infection or whether to consider antiviral therapy. The calculator is freely available on the MFMU Network website external link.

Reference

Rouse DJ et al. Noninvasive prediction of congenital cytomegalovirus infection after maternal primary infection external link. Obstetrics & Gynecology DOI: 10.1097/AOG.0000000000004691 (2022)