Primary CMV infection acquired during pregnancy is associated with a risk of foetal anomalies such as visual loss, sensorineural deafness, and cognitive impairment. Primary CMV infection is often asymptomatic, hence many women may not know they have been infected. Such infections are particularly common in women working with children such as primary school teachers and day care nurseries.
The prevalence of CMV infections rises with age. Subjects can be re-infected with a different strain or have re-activation of the original CMV strain- CMV is after all a herpesvirus and therefore establishes latency, just like EBV or HZV. It is important to clarify here that the risk of foetal anomalies only arises for primary CMV infections acquired during pregnancy rather than re-infections or re-activation of the virus. CMV infection picked up even shortly before pregnancy do not affect the foetus.
Why should this be so? It is thought that existing antibodies to CMV following a previous infection offer protection against the virus being passed on to the foetus. Thus, longstanding maternal antibodies against CMV bind the viral antigens with a high avidity and protect the foetus.
However, this does not apply for primary infections acquired during pregnancy. Antibodies formed following a recent infection initially bind the viral antigens with low avidity for the first 3-4 months. After this period, due to a process of B-cells with higher antigen specificity being positively selected, a process called affinity maturation, the avidity of CMV antibodies for the virus increases.
This differential avidity is used as an index (Avidity Index or AI) for the recency of CMV infection. Thus low avidity of IgG antibodies for a CMV viral lysate indicates a primary CMV infection within the last 3-4 months, while high avidity indicates one of 3 possibilities- either that the primary infection occurred more than 6 months ago, or that this was a re-activation of a previous primary infection, or that this is a new infection with a different strain of CMV.
The reason this metric is used to gauge the recency of CMV infection is because of the uselessness of IgM antibodies to CMV as a marker of recent infection. Not only can anti-CMV IgM be formed following other viral infections (cross-reactivity), but the IgM isotype can persist for several months after CMV infection, and as such would be of no value in determining if the infection picked up by a woman was acquired during pregnancy or before pregnancy. Thus, isolated IgM antibodies to CMV are of no diagnostic value.
When IgM antibodies to CMV co-exist with the IgG isotype however, the possibility of recent infection cannot be ruled out. It is in these instances that avidity of IgG is utilised. Low avidity (AI <50) is taken as an indication of primary infection within the last 4 months, while high avidity (AI >60) is compatible with infections> 6 months ago. Intermediate values of 50-60 can be seen with primary infections that happened 4-6 months ago.
High avidity tests obtained in the 1st trimester are reassuring. However when the IgG antibodies picked up in 2nd or 3rd trimester display high avidity for the viral lysate, it is not possible to rule out the possibility that the primary CMV infection occurred within the 1st trimester. In such cases, amniotic fluid may have to be obtained and tested for CMV DNA.
Although the IgG avidity test is used mainly in pregnant women, there is no reason it cannot be used in other populations. An example of this would be a sexually active adolescent with unexplained transaminitis, perhaps following an episode of fever, who has tested positive for both IgG and IgM antibodies against CMV. A low avidity test makes it highly likely that the deranged LFTs were due to primary CMV infection.
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