Amsterdam institute for Immunology and Infectious Diseases

Half of the Dutch population is unknowingly infected with the cytomegalovirus (CMV), belonging to the group of herpes viruses. After infection, the virus hides in the body, just as other herpes viruses do. In most people, the infection remains harmless; they do not get sick. The situation is different for pregnant women. If they contract a CMV infection, or have a flare-up of dormant CMV after a previous infection, the virus can infect the unborn child. And if that happens in the first three months of pregnancy, it can lead to hearing damage and neurological abnormalities in the child.

Every year, about 850 children are born in the Netherlands with what is called a "congenital CMV infection." The vast majority of children have no symptoms or complaints. But in just under a quarter, the infection results in developmental delays or other neurological problems; most suffer hearing damage. Sometimes these symptoms are noticeable immediately after birth, sometimes they are barely noticeable at first but worsen in the first years of life.

Diversified picture of complaints

‘We know that CMV has a predilection for the brain of the unborn child,’ Dasja Pajkrt, Professor of viral pediatric infectious diseases at Amsterdam UMC (Amsterdam UMC) explains. ‘Besides neurological symptoms, the virus can cause a diverse picture of symptoms, with anemia, liver inflammation or platelet deficiency. However, we are still in the dark about why the symptoms vary from child to child, let alone why they sometimes worsen.’

To know which of the more than 170,000 children born annually in the Netherlands are at risk, you would have to test all pregnant women for CMV. That seems complicated, but nothing could be further from the truth, as such a test could easily benefit from other studies. Around 12 weeks of pregnancy, a tube of blood is taken from the mother to test for antibodies to hepatitis b, HIV and syphilis. 'A determination for CMV antibodies would be an excellent addition to that,' says Ann Vossen, physician-microbiologist at Leiden University Medical Center (LUMC). 'Based on the type of antibodies, we can even determine approximately when someone had a CMV infection.'

Child blood test

In addition, for CMV screening, the so-called NIPT (non-invasive prenatal test), a blood test of the child for genetic abnormalities, such as Down syndrome, can also be used. NIPT also comes early in pregnancy: around the 11th week. "We can test for CMV by measuring the genetic material of the virus in the blood," Dr. Vossen says. 'An additional advantage is that you immediately see how much virus the mother has in her body. The more virus, the greater the risk of infecting the child.'

Nevertheless, CMV is not tested for in the Netherlands, much to Dr. Vossen's frustration. The reason: if you introduce screening, it should also have consequences, for example in the form of treatment. Moreover, for the vast majority of children who become infected with CMV in the womb, there are no consequences. 'The difference with HIV, hepatitis b or syphilis is that 9 out of 10 children infected with CMV in utero are symptom-free,' says Prof. Pajkrt. In addition, with HIV, adequate treatment is possible for the pregnant woman, thus preventing infection of the baby. Prof. Pajkrt: 'With CMV, no such treatment exists yet. And we in the Netherlands believe that if you introduce a test, you should also be able to offer perspective.'

To screen or not to screen?

In other countries, CMV testing does occur, and treatment is even available. In some regions in Italy, France and Spain, all pregnant women are screened for CMV. If the infection is detected, they are given a dose of the antiviral drug valaciclovir that is high enough to reach the child via the placenta. The idea is twofold: the drug should protect the unborn child from infection or prevent further damage in the child if an infection has already occurred.

That approach is controversial, Dr. Vossen says. 'The side effects on the child are still unpredictable, and we also don't know whether the treatment is useful at all. That's why we don't dare give it in the Netherlands.' Practitioners and researchers in said countries want to give mothers and children a solution. That's distorted, Dr. Vossen says. 'Some want to advance as quickly as possible, while we think the evidence lags behind.'

"There are no studies proving the effectiveness of valaciclovir in CMV infection," Prof. Pajkrt adds. The approach itself does deserve more research, she believes. "As with HIV, you want to prevent the infection of the unborn child by getting and keeping the amount of virus in the mother as low as possible. A drug that may not exist now could be effective."

Testing after birth

Dr. Vossen is investigating whether children infected with CMV can still be treated after birth to counteract the potentially serious consequences of the infection. This is already happening in Belgium, where a saliva test for CMV is available for newborns. If that test shows an infection, the baby's urine is also tested for CMV. If that is also positive, the child is given a course of the antiviral drug ganciclovir. That would limit the damage of the CMV infection, but again, its actual effectiveness has not yet been demonstrated.

Dr. Vossen takes a slightly different approach. She examines newborn children with CMV infection who score inadequately on neonatal hearing screening. This is a hearing test that every baby receives in the first weeks after birth. In it, an employee of the child's health care center measures whether the eardrum can pass sounds. "If the child didn't pass the hearing test, they are given a six-month screening treatment with ganciclovir," Dr. Vossen explains. Dr. Vossen: 'The results have not yet been published, but our first impression is that this treatment after birth prevents more serious hearing loss later in life.'

Vaccinnation

While waiting for a CMV test as well as an effective treatment during or after pregnancy, Dr. Vossen and Prof. Pajkrt are hoping for a vaccine against CMV. "There are several candidates, but developing them into a registered vaccine will take years," Dr. Vossen says. 'Moreover, the CMV virus hides from the immune system and therefore the vaccine has less grip on it. As a result, it may take a long time before we see an effect.'

'A vaccine for all fertile women can protect unborn children from CMV from the beginning of pregnancy,' Prof. Pajkrt also believes. But, she says, much more can be done on prevention anyway, through better hygiene. Washing with soap and water is enough to destroy the virus. "So wash your hands after contact with a child's bodily fluids, don't kiss a child on the mouth and don't share pacifiers or cutlery," Pajkrt says. "If enough awareness is raised about the risk of CMV during pregnancy, screening may not even be necessary."

Herpes viruses, dormant infections

The cytomegalovirus (CMV, cyto = cell, megalo = large) gets its name from the characteristic swelling of body cells after they are infected. Like other herpes viruses, CMV can escape the immune system by hiding somewhere in the nervous system.

After the acute phase of the infection, herpes viruses can remain dormant in the body for years, but when resistance is lowered, they can flare up again. A well-known example is cold sores. Flare-up of CMV is a problem in healthy pregnant women, but especially in transplant patients, where it can cause life-threatening inflammation in the intestine, lungs or liver.

For more information contact Prof. Dasja Pajkrt.

Source: read the original (Dutch) article by Koen Scheerders on NRC.nl here.