Editorial Commentary: Maternal Laboratory Assessment and Fetal Risk of Cytomegalovirus Infection

Abstract

Congenital cytomegalovirus (CMV) infection is a leading cause of hearing, cognitive, and motor disability in children for which medical science has yet to provide prevention or cure. Although vaccines aimed at prevention of congenital infection are being developed, there are significant challenges to be overcome and it could easily be a decade or longer before a CMV vaccine is licensed for prevention of maternal or congenital infection. The source of CMV infection for a young mother is often within her own family (eg, a child who acquired CMV in day care or an intimate partner), making prevention by limiting exposure particularly difficult. When primary CMV infection is identified during pregnancy, management options are limited. Passive immunization with CMV immune globulin has been studied as a means to prevent fetal infection in pregnant women with primary CMV infection [1]. This expensive intervention is now being offered to pregnant women, although convincing evidence of efficacy is lacking. Accurate diagnosis and timing of maternal infection is a prerequisite for counseling pregnant women with gestational CMV infection on the risks and possible consequences of fetal infection. Leruez-Ville et al examined data from nearly 5000 women who were screened for CMV infection at the first prenatal visit to determine whether markers for recent CMV infection could be used to predict occurrence of fetal infection [2]. Women were tested for antibody to CMV prior to the 14th week of gestation. Sera that were positive for both immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody were then tested for CMV IgG antibody avidity using 2 commercially available assays. Seventy-two women had low or intermediate results on the avidity tests, further evidence of first-trimester primary infection. Maternal serum from this group was tested for CMV using real-time polymerase chain reaction (PCR), and amniotic fluid or newborn urine was tested for CMV by PCR. In the group of women with first-trimester CMV infection (CMV IgM positive, low or intermediate avidity), fetal infection was found in 26% of those with low CMV IgG avidity and 6% of those with intermediate avidity. Maternal serum PCR was positive in 80% (8/10) of cases with fetal infection compared with 23% (7/30) with no fetal CMV infection. The combination of avidity and maternal serum PCR results appeared to improve the ability to predict fetal infection among women with serological evidence of first-trimester primary CMV infection. This study provides further evidence that among pregnant women who are tested for CMV infection, widely available laboratory tests can identify those who are most likely to have primary CMV infection, and more important, those who have greater risk of transmitting CMV to the fetus. This information could be of clinical value for physicians who have the difficult task of counseling or guiding the prenatal care of a pregnant woman who was found to be CMV IgM antibody positive. Although the approach studied by Leruez-Ville et al should be reproducible anywhere similar laboratory capability is available, the probability for fetal infection based on specific laboratory results will likely vary where different laboratory methods or commercial assays are used. The 2 commercial assays used to measure CMV IgG avidity in Leruez-Ville et al’s study gave quite different results for intermediate avidity level. With the VIDAS assay, 67% of samples from CMV IgM– positive sera had intermediate avidity compared to only 19% with the LIAISON