A new study indicates that noninvasive prenatal screening (NIPS) performed using a low-cost form of whole genome sequencing can detect the risk in pregnant mothers of transmitting cytomegalovirus (CMV)—a common herpes infection that can cause permanent hearing loss—to their developing babies.
The findings, published in Clinical Chemistry, could help doctors identify which pregnant patients would benefit from receiving antiviral treatment, thereby preventing mother-to-fetus transmission of the virus.
In addition to ear damage, CMV can trigger neurodevelopmental delays and other irreversible problems in up to 20% of infants born with it. The infection occurs in about 1 in 150 live births globally. Despite its prevalence, current guidelines do not recommend prenatal screening for CMV, largely because no effective therapies have been available to treat it.
However, that is changing. In 2020, research showed the antiviral drug valacyclovir can reduce CMV transmission by more than 70% when given to infected women in their first trimester of pregnancy. While the Food and Drug Administration has not formally approved valacyclovir for this use, many doctors prescribe it to pregnant patients known to have CMV.
The new study provides powerful evidence that NIPS—which is already routinely used during pregnancy to detect chromosomal abnormalities—can also gauge CMV infection in both mother and baby. Researchers from Belgium led by Dr. Geert A. Martens analyzed NIPS data from 22,333 pregnancies at 12–14 weeks’ gestation between November 1, 2019, and January 1, 2025.
NIPS was done using a cost-effective method called low-pass whole genome sequencing, which assesses a patient’s genetic blueprint. The researchers evaluated the blood samples found to include genetic material from non-human sources like viruses and bacteria for free-floating fragments of DNA (called cell-free DNA) from CMV.
They found CMV DNA in 2.1% (462) of the pregnancies studied. The researchers divided those patients’ blood samples into four groups based on the amount of viral DNA detected, ranging from least to most. They validated this information by comparing it to results gleaned using PCR, the gold-standard method for measuring DNA.
The results showed that the NIPS-derived CMV data showed good diagnostic accuracy for maternal and newborn CMV infections. In other words, a positive CMV result was a strong indicator of infection among mothers (confirmed by antibody testing) and their newborns (confirmed through a systematic screening program). The risk for maternal and newborn (or congenital) CMV infection was highest in blood samples from pregnancies with the most CMV DNA.
“Crucially, our study is the first to directly link NIPS-derived CMV read counts to both maternal serostatus and confirmed cCMV [congenital CMV] outcomes from a systematic newborn screening program, in a real-world high-volume setting of first-tier cell-free fetal DNA screening,” the researchers stated. While more research is needed to flesh out the clinical significance of the findings, these results are promising.
“Given its low cost and high throughput, [the integration of CMV DNA testing] into routine aneuploidy screening is a powerful complement to serology, poised to improve the identification of pregnancies that may benefit from antiviral therapy to prevent cCMV,” the authors wrote.
Publication details
Pauline H Herroelen et al, Universal Screening of Cytomegalovirus Viral Load by Low-Pass Whole-Genome Sequencing in First-Trimester Pregnancy: Clinical Validation, Clinical Chemistry (2025). DOI: 10.1093/clinchem/hvaf159
Journal information:
Clinical Chemistry
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Association for Diagnostics & Laboratory Medicine (ADLM)
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