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Pregnant women in the Netherlands are not screened for cytomegalovirus infection, which is dangerous to the unborn child, because there are no treatment options. Now treatment seems possible and research by Brigitte Faas and colleagues shows the infection can be detected with the already existing NIPT test, the perspective may be shifting.
Cytomegalovirus (CMV) is a herpes virus that infects almost everyone during life. It rarely causes severe problems in healthy people, but there is one major exception: when the fetus is infected during the first trimester of pregnancy. "At that age, the fetus still has to develop completely and the virus can seriously disrupt that development," says Radboudumc researcher Brigitte Faas. "Hearing loss or deafness is the most common symptom after fetal infection. Developmental delay, spasticity and growth retardation can also occur, and in severe cases the fetus may die before birth. This makes CMV infection in pregnant women a serious risk to the unborn child." In pregnant women with an active infection in the first trimester, about 35 percent of fetuses become infected.
No screening
While some of the infected children die before birth, in the Netherlands annually also some 1000 children are born, who are infected with the virus during pregnancy. About 180 of them are left with permanent defects, which is roughly equal to the number of children with Down syndrome born each year. Although pregnant women can be screened for Down syndrome, there is no screening for CMV in the Netherlands, primarily because no treatment is available. Without treatment screening makes little sense, one finds. But this could soon change.
Antivirals
In recent years several international research groups have reported that antivirals can prevent transmission of the virus from the mother to the unborn child. This has caused Faas to explore the feasibility of large-scale screening for CMV in pregnant women. "For efficient treatment, you need to know as soon as possible whether a pregnant woman is carrying an active infection. It means you would have to screen all pregnant women, about 170,000 per year in the Netherlands. You can set up a separate screening program for this, but you can also use the Non Invasive Prenatal Test (NIPT), which has been available to all pregnant women in the Netherlands since April 1, 2017. With NIPT, the blood of pregnant women is searched for DNA fragments that indicate Down, Edwards or Patau syndrome in the fetus."
Screening?
About ten percent of the DNA fragments in the pregnant woman's blood come from the placenta/fetus, about ninety percent from the mother herself. But there is even more data locked up in the NIPT! Faas: "You can also find fragments of viruses, such as parvoviruses and - indeed - CMV." That's exactly what Faas started investigating, working closely with NIPT experts Jasper Linthorst and Erik Sistermans of Amsterdam UMC. In the data stored at the three NIPT centers in the Netherlands - Erasmus MC, Amsterdam UMC and Maastricht UMC/Radboudumc - Faas looked whether CMV could be detected with NIPT.
Reliable NIPT
"In the vast majority of the more than 200,000 NIPT tests we examined, we found no CMV. In a very small proportion we did," says Faas. "We then used the current standard methods for detecting CMV infections to see what this means. In all negative results - that is, without CMV - that we checked, there was indeed no active CMV infection. Recently active or still active CMV infections we only saw in a portion of the samples in which CMV was found." This means that NIPT can also be used to detect CMV infections early in pregnancy.
Large-scale nationwide study
The perspective for screening for CMV during pregnancy could change by the possibility of treatment combined with the results of this NIPT study, now published in eBioMedicine. In this way, a completely new screening doesn’t need to be set up. Faas: "This study certainly points in that direction, but to get to the bottom of it, we would like to set up a large-scale national study, in close collaboration with RIVM and other stakeholders, in which we immediately include the effect of antiviral drugs. Now over sixty percent of pregnant women use the NIPT, which means that just under forty percent do not. A point of attention in such a study should therefore also be how those forty percent can still be offered screening for CMV. But based on the treatment options and the research now published, we believe that screening for CMV should be put on the agenda."
Paper eBioMedicine: Early detection of active Human CytomegaloVirus (hCMV) infection in pregnant women using data generated for noninvasive fetal aneuploidy testing - Brigitte Faas, Galuh Astuti, Willem Melchers, Annette Reuss, Christian Gilissen, Merryn Macville, Stijn Ghesquiere, Leonieke Houben, Malgorzata Ilona Srebniak, Geert Geeven, Janette Rahamat-Langendoen, Erik Sistermans, Jasper Linthorst
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Pieter Lomans
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