Inactive CMV can cause deafness in children

Half of the population of the Netherlands – without knowing it – is infected with the cytomegalovirus (CMV). After infection, the virus hides in the body, just like other herpes viruses. The infection remains harmless in most people. They don’t get sick.

It is different for pregnant women. If they become infected with CMV, or develop a dormant CMV outbreak after a previous infection, the virus can infect the unborn child. If this occurs in the first three months of pregnancy, it may lead to hearing damage and neurological abnormalities in the child.

Every year in the Netherlands around 850 babies are born with a so-called “congenital CMV infection”. The vast majority of children have no symptoms or complaints. But in just under a quarter, the infection leads to developmental delays or other neurological problems. Most of them suffer from hearing loss. Sometimes these symptoms can be noticed immediately after birth, and sometimes they are hardly noticeable at first but worsen in the first years of life.

Various pictures of complaints

“We know that CMV has a tendency to infect the brain of the unborn child,” says Dasja Bajkert, professor of childhood viral diseases at UMC Amsterdam. In addition to neurological complaints, the virus can cause a diverse picture of complaints, such as anemia, hepatitis or thrombocytopenia. But why each child’s symptoms are different, not to mention sometimes exacerbated, we don’t know yet.”

To find out which of the more than 170,000 babies born in the Netherlands each year are at risk, you must test all pregnant women for CMV. This is less difficult than it sounds, because such a test could easily be based on other studies. At around 12 weeks of pregnancy, a tube of blood is taken from the mother to check for antibodies to hepatitis B, HIV, and syphilis. Identifying CMV antibodies would be an excellent addition to that, says Ann Vossen, a medical microbiologist at LUMC. “We can even determine if someone has a CMV infection based on the type of antibody.”

A blood test in a child

In addition, the so-called NIPT (Non-Invasive Prenatal Test) can also be used to screen for CMV, which is a blood test for a child to detect genetic abnormalities, such as Down syndrome. NIPT also comes in early in pregnancy: around the 11th week. “We can test for CMV by measuring the genetic material of the virus in the blood,” Vossen says. An added bonus is that you can immediately see how much virus the mother has in her body. The higher the virus, the greater the risk of infection for the child.

Despite this, there is no test for CMV in the Netherlands, much to Vossen’s frustration. Reason: If you introduce an examination, it must also have consequences, for example in the form of treatment. Moreover, for the vast majority of babies who become infected with CMV in the womb, there are no consequences. “The difference with HIV and hepatitis B or syphilis is that 9 out of 10 babies infected with CMV in the womb don’t have symptoms,” Bajkert says. In addition, appropriate treatment can be given to a pregnant woman in the event of HIV infection, so that infection of the child can be prevented. “There is no such treatment yet for CMV. And we in the Netherlands believe that if you give a test, you should also be able to give a perspective.”

To check or not?

In other countries, testing is not done, and there is even treatment available. In some regions of Italy, France and Spain, all pregnant women are screened for CMV. In the presence of a proven infection, they are given a dose of the antiviral drug valacyclovir, which is so high that it also reaches the baby through the placenta. The idea is twofold: The medicine should protect the unborn baby from infection or prevent further harm to the baby if there is already an infection.

Vossen says this approach is controversial. Side effects on the child are still not expected, and we don’t know if the treatment is helpful at all. This is why we dare not give it in the Netherlands.” Practitioners and researchers in these countries want to give mothers and children a solution. This is distorted, says Vossen. “Some want to move forward as quickly as possible, while we think the evidence is lagging.”

“There are no studies demonstrating the efficacy of valacyclovir in CMV infection,” Bajkert adds. You think the same approach deserves more research. “Just like HIV, you want to prevent infection of the fetus by reducing the amount of virus in the mother and keeping it as low as possible. A treatment that doesn’t exist yet can be effective.”

Postpartum testing

Vossen is investigating whether babies infected with CMV can be treated after birth in order to counteract the potentially serious consequences of infection. This is already happening in Belgium, where a saliva test for CMV virus is available for newborns. If this test reveals an infection, the child’s urine will also be tested for CMV. If it is also positive, the child will receive a course of the antiviral drug ganciclovir. This would limit the damage of CMV infection, but here too the actual efficacy has not yet been demonstrated.

Vossen takes a slightly different approach. Newborns with CMV infection who fail to achieve adequate results in newborn hearing screening are studied. This is a hearing test that every baby receives in the first weeks after birth. An employee at the counseling office measures whether the eardrum can transmit sounds. Vossen explains that if a child does not pass a hearing test, they will receive a study treatment for six months with ganciclovir. “The results have not yet been published, but our first impression is that this treatment after birth prevents severe hearing loss later in life.”

vaccination

While waiting for CMV testing and effective treatment during or after pregnancy, Vossen and Beckert hope to have a vaccine against CMV. “There are many candidates, but it will take years to develop them into a patented vaccine,” Vossen says. In addition, the virus hides from the immune system and the vaccine has less control over it. As a result, it may take a long time before we see an effect.”

Bagkert also believes that “a vaccine for all fertile women can protect the fetus from CMV from the very beginning of pregnancy.” But she says a lot can be done about prevention anyway, by improving hygiene. Washing with soap and water is sufficient to kill the virus. “Wash your hands after coming into contact with the baby’s bodily fluids, don’t kiss the baby on the mouth, and don’t share pacifiers or cutlery,” says Bagkert. “If there is sufficient awareness of the risk of CMV infection during pregnancy, screening may not be necessary.”

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