Prevention, workup and management of CMV in pregnancy

The document is divided into two parts:
The obstetric part – how to prevent, workup and manage cytomegalovirus infection in pregnancy. These guidelines institutionalize the entire aspect of CMV screening during pregnancy in a way that affects all pregnancies.
The pediatric part – how to workup and manage babies with congenital CMV infections. I will not be reviewing this part in this chapter.

Therefore, the purpose of this current chapter is to summarize the obstetric part of the guidelines, especially the “new” part about screening pregnant women for this virus.

Why is it important to think or deal with CMV in pregnancy?

Several reasons to this:
a. Prevalence – about 0.5-1% of babies in the western world are born with this congenital infection, a large proportion of them as a result of a primary infection in the mother during pregnancy.
b. Importance – congenital CMV in babies is the most common non-genetic cause of hearing loss (up to complete deafness) and lots of further potential morbidity.
c. It is a preventable and treatable infection – there are way in which the primary maternal infection in pregnancy can be prevented and ways to treat women who are experiencing a primary infection. That is why is it is worth screening pregnant women.
Note the important difference between prevention and treatment, we will dig in to this below.

What is a primary infection and what is a non-primary CMV infection in pregnancy?

According to several epidemiologic research studies conducted in many western countries, about 80% of fertile women will have already experienced a CMV infection in the past. Some know and remember having been sick and others do not. You can find out whether you have had the infection in the past by performing a serology test that is performed at the beginning of the pregnancy (or right before pregnancy).
About 20% of women in my country will get pregnant having had no prior antibodies to CMV (no medical history of a past infection).
Primary CMV infection in pregnancy – a woman that has not had the infection in the past and gets the infection for the first time during pregnancy. Since she does not have any antibodies, the infection can pass the placenta and expose the fetus to the risk of infection, especially if it occurs during the first few months of pregnancy.
Non-primary CMV infection in pregnancy – a woman who has antibodies (has had the CMV infection prior to the pregnancy) but the virus reactivated during the pregnancy and infects her again, or a woman who previously experienced a different type of CMV. In these situations, the virus can still be transmitted to the fetus but the risk of harm to the fetus is much lower than in the primary infection.

How can you tell whether or not a woman has had a CMV infection in the past?

A serological test for CMV performed on the woman’s blood.
There is an antibody referred to as the IgG antibody – if it is positive, then it means that the person has been previously exposed to the virus and they are considered immune. It does not matter whether it is positive because of an exposure that occurred years prior to the test or only 6 months before the test was taken.
The IgM antibody – this is more relevant to an acute infection and does not help us determine whether the woman experienced the infection in the past or not.

Is there a difference in the clinical guidelines for women with a positive serology from prior to pregnancy compared to one with a negative serology?

Absolutely. The difference is essential when it comes to screening purposes.
For the first time in my country, women with a negative serology or an unknown serology will be asked to undergo several tests during pregnancy to find out whether they got the infection. A woman with a medical history of infection in the past (past antibodies) – the guidelines do not require her to undergo further tests during pregnancy.
Find out more below.

Screening women for CMV infection in pregnancy – women with positive serology for past infection

In these situations, there is no need to undergo further tests during pregnancy.
Additionally, it is possible that in the near future, certain health organization that took part in writing these clinical guidelines, will cancel any test that they receive for women who have had a previous positive serology for past infection. I think this is the right thing to do, because a repeat serology for someone who was previously found to be positive is not helpful in determining whether the person is experiencing a recurrent infection and often just complicates things system-wise.
A woman who has had a previous infection should only be tested in exceptional situations, following consultation with a specialist.

Screening women for CMV infection in pregnancy – women with negative serology for past infection

This is where the revolution occurred. In women with negative serology or those whose status is unknown.
Women who seek pre-natal consultation, prior to pregnancy or fertility treatment, CMV serology should be tested for as soon as possible.
If the tests are not performed prior to pregnancy, or if the woman is known to not have experienced the infection in the past, CMV serology tests should be conducted in the beginning of the pregnancy or as soon as possible, preferably in the first trimester.

Okay, I am in the beginning of my pregnancy and my serology tests are negative – what should I do?

Two important things.
a. Prevent a CMV infection – find out more below.
b. Repeat the serology tests at least once to two times during pregnancy – during the 11-14th week of pregnancy (together with your first biochemical screening test) and during weeks 16-19 (together with you second biochemical screening test).

What should I do after the 20th week of pregnancy?

A woman who has undergone all the above tests and remains negative does not need to repeat the test after the 20th week. This is because the risk of fetal infection after this time as a result of a maternal infection is very low and negligible.

What about an additional pregnancy with a negative serology again?

Repeat the above protocol, once more.

How can you prevent a primary CMV infection in pregnancy?

Fortunately, I reviewed this topic before these guidelines were published.
Find out more here about the five (relatively) simple rules to help prevent a primary CMV infection in pregnancy in a woman who has not experienced the infection in her past.

Can we prevent a non-primary CMV infection in pregnancy?

As I have previously explained, a non-primary infection can occur through one of two mechanisms:
A reactivation of the latent primary virus in the mother – this cannot be prevented.
A new CMV infection – there is no evidence for this in the scientific literature, but it is probably reasonable to think that the five rules described above would prevent this type of infection.

What if a CMV infection were to occur during pregnancy?

Fortunately, this website also has a summary of an Israeli paper that demonstrated the efficacy of Valacyclovir therapy in women following an early infection during pregnancy.
Therefore, the new clinical guidelines also has a summary about this and recommends treatment with antiviral medication in women who are found to have experienced an early primary CMV infection.
But this is a more advanced topic that we reserve for the professionals.

How can we summarize the clinical guidelines then?

# Women who are planning a pregnancy are recommended to undergo CMV serology tests prior to getting pregnant.
# If a woman is found to have a negative serology or does not have any previous tests, CMV serology tests are recommended during the beginning of her pregnancy.
# There is no need to screen women who are found to be IgG positive prior to their pregnancy.
# Women with a negative serology will receive counselling on how to reduce their risk of infection (the 5 rules).
# Women with a negative serology in the beginning of their pregnancy will be required to repeat the tests during the 11-14th weeks and 16-19th weeks of pregnancy (at the very least).

What else is important?

Let’s emphasize that prevention of the infection is better than management or treatment, so try to adhere to the 5 rules so that together we can help reduce congenital CMV infections.

In summary, my country is becoming one of the first countries to incorporate CMV screening during pregnancy. I think this is very exciting. What is left for us to see is how the large healthcare organizations implement these guidelines in each and every pregnancy.
And if you are in the beginning of your pregnancy, remember that there is another infection that we would like to prevent and that is toxoplasma in pregnancy.

All the best.