Abstract
Congenital human cytomegalovirus (HCMV) is the most common viral infection of the developing fetus, and a significant cause of neurodevelopmental abnormalities in infants and children. Congenital HCMV infections account for an estimated 25% of all cases of hearing loss in the US. It has long been argued that maternal adaptive immune responses to HCMV can modify both the likelihood of intrauterine transmission of HCMV, and the severity of fetal infection and risk of long term sequelae in infected infants. Over the last two decades, multiple studies have challenged this paradigm, including findings that have demonstrated that the vast majority of infants with congenital HCMV infections in most populations are born to women with established immunity prior to conception. Furthermore, the incidence of clinically apparent congenital HCMV infection in infants born to immune and non-immune pregnant women appears to be similar. These findings from natural history studies have important implications for the design, development, and testing of prophylactic vaccines and biologics for this perinatal infection. This brief overview will provide a discussion of existing data from human natural history studies and animal models of congenital HCMV infections that have described the role of maternal immunity in the natural history of this perinatal infection.
Highlights
Congenital infection with human cytomegalovirus (HCMV; cCMV infection) is the most frequently reported viral infection in the newborn infant
Significant race-dependent disparities in the reported incidence of cCMV infections in the US suggest that additional undefined characteristics of maternal populations could contribute to the natural history of this perinatal infection [7]
A unique and as yet unexplained characteristic of cCMV infection is that its prevalence increases as the prevalence of HCMV infection increases in the maternal population, and fails to reach a level at which time the incidence of cCMV falls [8,9]
Summary
Congenital infection (present at birth) with human cytomegalovirus (HCMV; cCMV infection) is the most frequently reported viral infection in the newborn infant. In contrast to the clinically asymptomatic infection in pregnant women, intrauterine transmission to the developing fetus can result in devastating consequences, including fetal loss Such severe infections are relatively uncommon, and about 90% of infants infected in-utero exhibit no findings in the newborn period that would allow their identification by physical examination. Some of the more recent findings relative to the development of vaccines and biologics, to prevent or to reduce the incidence of damaging cCMV infections, will be reviewed in the context of decades old results Together, observations from these studies illustrate the complexity of the interactions between the host and HCMV in this congenital infection, and suggest that newer approaches to understanding the relationship between HCMV and maternal adaptive immunity could be required for the development of effective prophylactic vaccines and biologics
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