Prenatal diagnosis and prognosis of congenital cytomegalovirus (CMV) infection in pregnant women undergoing a primary CMV infection.

Each year approximately 1–7% of pregnant women acquire a primary cytomegalovirus (CMV) infection. Of these, about 30–40% transmit infection to their fetuses. Up until some years ago it was not possible to precisely define the maternal immune status through laboratory testing. Recent development of advanced serological tests now allow us to identify, among pregnant women with suspected CMV, those with primary infection who are therefore at higher risk of transmitting CMV to their fetus. Given the high risk of mother–fetus transmission and fetal damage, prenatal diagnosis is recommended, between 20-21 weeks’ gestation, to women with primary CMV infection contracted in the first half of pregnancy and/or in case of fetal abnormalities suggestive of infection. CMV-DNA detection in amniotic fluid (AF) distinguish uninfected from infected fetuses in primarily infected mothers (positive predictive value =100%). However it is still very difficult to determine which are the infected foetuses at higher risk of developing severe CMV disease. In this work we studied a cohort of 790 pregnancies at risk of in utero CMV transmission; 796 amniotic fluid (AF) samples were tested by real time PCR assay (qPCR) and virus isolation. AF samples were collected at 20-21 weeks' gestation and at least 6-8 weeks after the onset of maternal CMV infection. Outcome was fully documented in 714 newborns and 82 foetuses. A total of 108 newborns were CMV infected; 25 were 119 symptomatic and 83 asymptomatic. Comparing symptomatic and asymptomatic newborns, the mean viral load in AF was significantly higher in symptomatic newborns (mean values 2x10^6 vs 9.4x10^5, P=0.009). The 82 infected foetuses were divided in two groups: those with histological damage in the brain and in 2 or more organs and those with histological damage in only 2 or more organs. When qPCR disclosed more than 10^6 copies/mL of AF, 62.5% of foetuses had disseminated infection and brain damage compared to 29.4% of foetuses with disseminated infection alone. Although the highest median values of CMV-DNA in AF tend to indicate an increased risk of severe infection, high viral loads may be associated with symptomatic or asymptomatic congenital infections leading to the conclusion that a correlation between a high CMV load in AF and foetal/neonatal compromission is uncertain. Recent studies suggest that the determination of multiple markers (haematological, biochemical and virological markers) in foetal blood following virus detection in AF, is predictive of perinatal outcome of CMV infected foetuses. However our results do not completely confirm this. Therefore, one of the major limitations of CMV prenatal diagnosis is that we are not able to discriminate between infants who will or will not have symptoms at birth. Prognosis factors for CMV disease are still being researched. In this regards, we found interesting results studying the HLA-G antigen, which is a tolerogenic HLA-Ib molecule expressed during pregnancy. HLA-G expression is modified by CMV infection, with functional consequences in immuno-regulation. Data indicates that this molecule could be a biomarker of both maternal and foetal infection and leading to disease progression