Diagn. avidity is both a sensitive and Misoprostol a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. INTRODUCTION Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection, occurring in approximately 40,000 newborns each year in the United States (1,C4). The clinical manifestations include sensorineural hearing loss, visual impairment, mental retardation, and cognitive defects; 4% of infected infants do not survive Cd247 (1, 2, 5, 6). Several studies have demonstrated a strong link between primary CMV infection of the mother and CMV transmission. The risk of congenital infection is approximately 40% in babies born to mothers who acquire a primary (initial) CMV infection after conception; in contrast, the risk is only about 1% in infants born to mothers who have evidence of CMV infection (i.e., circulating CMV antibodies) before conception (1, 3, 6,C9). The few cases of CMV transmission in seropositive mothers reflect nonprimary CMV infections, defined as either viral reactivation or infection with a different strain of CMV during pregnancy (2, 3, 5). Preexisting maternal antibodies thus appear to offer substantial protection against congenital infection, most likely due to the ability of antibodies to control viremia (2, 9, 10). The established link between primary CMV infection during pregnancy and congenital infection makes identification of primary CMV infection an important goal in maternal and neonatal health care. However, 95% of pregnant women with primary CMV infection are asymptomatic and thus cannot be diagnosed on clinical grounds (3, 11). The most straightforward indicator of primary CMV infection is documentation of seroconversion during pregnancy, but this approach is rarely effective due to the lack of preconception antibody screening programs allowing the identification of seronegative women (3, 9). Initial studies thus focused on detection of CMV IgM, due to its known utility as a transient marker of primary infection (3, 9, 12). These Misoprostol studies showed that CMV IgM detection is a sensitive marker for primary CMV infection, but its specificity is relatively poor; only about 50% of CMV IgM-positive individuals have primary infection (the reasons for this low specificity will be discussed later) (3, 5, 9, 13,C15). These disappointing findings for CMV Misoprostol IgM led to a search for a different laboratory assay that could be used to identify primary CMV infection with high specificity, as well as sensitivity (2). Studies assessing CMV IgG avidity showed that low CMV IgG avidity is both a sensitive and a specific marker of primary CMV infection (1,C3). Indeed, CMV IgG avidity is increasingly considered the gold standard for distinguishing primary from nonprimary CMV infection (1, 11, 12, 16) and is being used worldwide to identify primary CMV infection during pregnancy (14, 17,C21). This minireview focuses on 4 aspects of CMV IgG avidity testing: (a) the definition Misoprostol of avidity and the basic methodology used in initial studies linking CMV IgG avidity and primary infection; (b) a summary of results from the major studies demonstrating the utility of CMV IgG avidity assessment in pregnancy, including the advantages of avidity testing over CMV IgM testing alone; (c) a discussion of commercially available CMV IgG avidity assays, including newer automated assays; and (d) current issues and controversies in diagnosing primary CMV infections during pregnancy. DEFINITION OF AVIDITY AND BASIC METHODOLOGY Avidity is defined as the aggregate strength with which a mixture of polyclonal IgG molecules binds to multiple antigenic epitopes of proteins (12). It gradually matures over several months, reflective of antigen-driven selection of B cells producing IgG of increasing affinity (3, 11, 12). IgG antibodies produced during the first few months following primary infection exhibit low avidity (i.e., they bind weakly to the antigen), whereas antibodies produced by 6 months postinfection exhibit high.