Natural History of Congenital Cytomegalovirus Infection in Highly Seropositive Populations

Abstract

Maternal preconceptional cytomegalovirus (CMV) immunity does not protect the fetus from acquiring congenital CMV infection (cCMV). Nonprimary infections due to recurrence of latent infections or reinfection with new virus strains during pregnancy can result in fetal infection. Because the prevalence of cCMV increases with increasing maternal CMV seroprevalence, the vast majority of the cases of cCMV throughout the world follow nonprimary maternal infections and is more common in individuals of lower socioeconomic background. Horizontal exposures to persons shedding virus in bodily secretions (young children, sexual activity, household crowding, low income) probably increase the risk of acquisition of an exogenous nonprimary CMV infection and fetal transmission. In addition, more frequent acquisition of new antibody reactivities in transmitter mothers suggest that maternal reinfection by new viral strains could be a major source of congenital infection in such populations. However, the exact frequency of CMV nonprimary infection in seroimmune women during pregnancy and the rate of intrauterine transmission in these women are yet to be defined. Usually, the birth prevalence of cCMV is high (≥7:1000) in highly seropositive populations. There is increasing evidence that the frequency and severity of the clinical and laboratory abnormalities in infants with congenital CMV infection born to mothers with nonprimary CMV infection are similar to infants born after a primary maternal infection. This is particularly true for sensorineural hearing loss, which contributes to one third of all early-onset hearing loss in seropositive populations. This brief overview will discuss the need for more research to better clarify the natural history of cCMV in highly seropositive populations, which, in almost all populations, remains incompletely defined.

Keywords: CMV seropositive mothers; congenital infection; cytomegalovirus; highly CMV seropositive populations; natural history.

Figure 1.

Estimates of the number of infants with congenital cytomegalovirus infection (cCMV) infection born in regions of high maternal cytomegalovirus (CMV) seroprevalence (Africa, China, India, Latin America) compared with the number of infants with cCMV born in areas of low to intermediate maternal CMV seroprevalence (North America, Europe) according to the expected proportion of cCMV resulting from maternal primary or nonprimary CMV infections. Calculation were based on population estimates for childbearing age females (15–35) and birth rates in each geographic region [11]. Based on available data specific for countries that are located in the regions noted above, mean birth prevalence rates of cCMV were estimated to be 6:1000 for North America and Europe and 9:1000 for Africa, China, India, and Latin America. The cCMV rate resulting from primary maternal infection was estimated to be 10% for the highly seropositive populations and 40% for those in low to intermediate seropositive populations with the remainder of cases of cCMV resulting from nonprimary maternal infection.

Figure 2.

Combined data obtained in cohorts of Brazilian neonates screened for congenital cytomegalovirus infection (cCMV) showing neonatal characteristics of infected infants and occurrence of hearing loss in symptomatic and asymptomatic infants with cCMV (data based on results from the references [31, 45, 46]). CI, confidence interval; CMV, cytomegalovirus.