SUMMARY We reviewed studies that reported results of systematic cytomegalovirus (CMV) screening on fetuses and/or liveborn infants. The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live-born infants with congenital CMV infection were symptomatic, but the inter-study differences in definitions of symptomatic cases limit the interpretation of these data. Non-white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections. In summary, CMV is a common congenital infection worldwide that can lead to permanent disabilities. There is an urgent need for interventions that can reduce the substantial burden of this often overlooked disease. Copyright # 2007 John Wiley & Sons, Ltd.

Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection

https://epub.ub.uni-muenchen.de/3201/1/002.pdf

A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus

Cytomegalovirus establishes a lifelong latent infection following primary infection that can periodically reactivate with shedding of infectious virus. Primary infection, reactivation and reinfection during pregnancy can all lead to in utero transmission to the developing fetus. Congenital CMV infections are a major cause of permanent hearing loss and neurological impairment. In this literature review, we found that CMV infection was relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100%. CMV seroprevalence tended to be highest in South America, Africa and Asia and lowest in Western Europe and United States. Within the United States, CMV seroprevalence showed substantial geographic variation as well, differing by as much as 30 percentage points between states, though differences might be explained by variation in the types of populations sampled. Worldwide, seroprevalence among non-whites tended to be 20-30 percentage points higher than that of whites (summary prevalence ratio (PR) = 1.59, 95% confidence interval (CI) = 1.57-1.61). Females generally had higher seroprevalences than males, although in most studies the differences were small (summary PR = 1.13, 95% CI = 1.11-1.14). Persons of lower socioeconomic status were more likely to be CMV seropositive (summary PR = 1.33, 95% CI = 1.32-1.35). Despite high seroprevalences in some populations, a substantial percentage of women of reproductive age are CMV seronegative and thus at risk of primary CMV infection during pregnancy. Future vaccine or educational campaigns to prevent primary infection in pregnant women may need to be tailored to suit the needs of different populations.

Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

Herpes simplex virus infections

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.

Varicella-zoster virus.

We studied the incidence of primary and recurrent cytomegalovirus infection in 3712 pregnant women--2698 of middle to high income and 1014 of low income--to determine whether there were differences in the effects on the fetus. In the higher-income group, 1203 women (45 per cent) did not have antibodies to cytomegalovirus and were therefore susceptible to primary infection, as compared with 179 women (18 per cent) of low income. Congenital infection occurred more often (1.6 vs. 0.6 per cent) in infants in the low-income group. In this group it was associated with recurrent maternal infection more often (in 82 per cent) than with primary maternal infection, whereas in the upper-income group, it was associated with primary maternal infection in half the cases. Altogether, there were 32 cases of congenital cytomegalovirus infection - 16 in each group. Whereas primary maternal infection resulted in fetal infection in only half the cases, it was more likely to ge associated with clinically apparent disease than was recurrent infection. When these cases were combined with 28 cases of congenital infection retrospectively identified at other prenatal clinics, five of 33 infected infants born after primary maternal infection had clinically apparent disease, as compared with none of 27 born after recurrent maternal infection. We conclude that congenital cytomegalovirus infection resulting from primary maternal infection is more likely to be serious than that resulting from recurrent infection, and is more likely to occur in upper socioeconomic groups.

Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection.

Congenital and perinatal cytomegalovirus infections.

Of unselected postpartum women, 39% reactivated cytomegalovirus in breast milk, vaginal secretions, urine, and/or saliva. Consumption of infected breast milk led to infection of 69% of the infants. Although there was some milk secretory immune response to this virus, it prevented neither viral shedding nor viral transmission. All infected infants chronically shed cytomegalovirus. However, no infants have yet demonstrated chronic sequelae. Two preterm infants did develop a significantly acute problem, pneumonitis, which did resolve. The possibility that an unnecessary and perhaps more severe illness might occur in low-birth-weight seronegative infants fed banked human milk from sources other than the mother is disturbing and needs resolution.

Cytomegalovirus Infection of Breast Milk and Transmission in Infancy

Maternal cytomegalovirus infection and perinatal transmission.

The risk of acquiring cytomegalovirus (CMV) from infected infants concerns pediatric health-care workers, particularly those who may be pregnant. We determined the prevalence of CMV antibody, and thus of past infection, in groups of medical students and house staff, nurses, and physicians, and in groups of pregnant and nonpregnant young women in the community. Although age, sex, and race influenced the results, occupation did not. We then estimated the exposure of the health-care workers by determining the prevalence of CMV infection in three groups of asymptomatic infants for whom they provided care; CMV was shed in urine or saliva of 1.6 per cent of newborns, 13 per cent of premature infants hospitalized for over a month, and 5 per cent of older infants seen in outpatient settings. When we determined the incidence of primary infection in the adult groups by retesting the seronegative members about two years later, we found that the annual attack rates in the medical students (0.6 per cent), house staff (2.7 per cent), and nurses (3.3 per cent) were not higher than in young women in the community (2.5 per cent during pregnancy and 5.5 per cent between pregnancies). We conclude that although pediatric health-care workers frequently and unknowingly care for infants shedding CMV, this occupational contact confers no greater risk than that faced by young women in the community at large.

https://www.nejm.org/doi/pdf/10.1056/NEJM198310203091604?listPDF=true

Meyer E. Dworsky

Papers

Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection.

Congenital and perinatal cytomegalovirus infections.

Cytomegalovirus Infection of Breast Milk and Transmission in Infancy

Maternal cytomegalovirus infection and perinatal transmission.

Occupational Risk for Primary Cytomegalovirus Infection among Pediatric Health-Care Workers