Serologic surveys in the United States and Great Britain have shown that antibodies to CMV can be found in the sera of 40% to 60% of adults of middle or upper socioeconomic status, and in as many as 80% of those in lower socioeconomic groups (326). CMV seroprevalence is as high as 90% to 100% in pregnant women from Brazil, Chile, Korea, Japan, and the Ivory Coast (322,327). The higher the prevalence of maternal CMV antibody in a population, the greater is the rate of congenital CMV infection (326). Factors correlating with CMV seropositivity in pregnant women in the United States include non-Caucasian race, unmarried status, lower educational and income levels, and increasing parity (328,329). Sexual activity is an important risk factor for CMV infection in adolescents and
young adults, and coinfection with bacterial vaginosis, trichomoniasis, gonorrhea, or other pathogenic organisms increases the odds of intrauterine CMV transmission (330,331,332,333,334).

Intrafamilial CMV transmission from young children to their seronegative pregnant mothers can occur. The risk of CMV seroconversion for a seronegative mother with an infected child is estimated at 10% to 30% per year and is even higher if the child is younger than 20 months of age (326,335). Annual seroconversion rates for seronegative day care providers is about 8% to 12% (336,337). Health care workers with CMV-infected patient contact do not appear to be at increased risk of CMV acquisition compared with persons without patient contact (338).

About 0.7% to 4.1% of susceptible women acquire primary CMV infection during pregnancy, a risk comparable to that of nonpregnant women (322). Seropositive women can reactivate their latent CMV infection during pregnancy or, less commonly, become reinfected by an exogenous CMV strain. Cervical and urinary CMV excretion increases as pregnancy advances from the first to the third trimester (339). Pregnant women may shed CMV from the cervix, urinary tract, throat, and breast milk in the postpartum period (10).

Primary and recurrent maternal CMV infection can result in transmission of the virus to the fetus. This occurs in about 40% (range 24% to 75%) of pregnancies complicated by primary CMV infection (338). The presence of maternal antibodies to CMV in women with recurrent infection does not prevent viral transmission to the fetus, but it does reduce the risk of fetal infection and protects against major fetal damage by CMV (340,341). Severe congenital CMV after maternal reactivation or reinfection by other strains can occur, but is infrequent (342,343,344,345,346,347,348,349,350). For women who seroconvert between deliveries of successive infants, the risk of transmission of CMV to their offspring is 25%, 10%, and 4.2% when the interval is 24 months or shorter, 25 to 48 months, and more than 48 months, respectively (351).

Most women (90%) with primary CMV infection are asymptomatic, and the rest usually have illnesses resembling infectious mononucleosis (352). In a series of 102 pregnant women with primary cytomegalovirus infection referred to a tertiary care center in Rome, Italy, common symptoms noted were fever (42%), weakness (31%), myalgias (21%), and influenza-like illness (24%). Relative lymphocytosis of 40% or higher was found in 39%, and mild elevations in at least one aminotransferase level was measured in a third of the women (353). Other manifestations are rare but include interstitial pneumonia, myocarditis, aseptic meningitis, encephalopathy, retinitis, hepatitis, colitis, thrombocytopenia, and hemolytic anemia (354,355). Primary CMV infection during the first trimester of pregnancy does not cause fetal loss (356).

Infection can be documented by isolating the virus from urine, saliva, buffy coat, or cervical secretions (357). Viral isolation, however, does not differentiate between primary and recurrent CMV infections. Measurement of CMV-specific IgM antibodies is useful for the diagnosis of primary infection, but this antibody can persist in serum for 4 to 8 months (358). Furthermore, CMV-specific IgM can appear after primary and reactivated infection (357). CMV-specific IgG antibody levels are helpful if seroconversion or a fourfold titer rise can be demonstrated. The IFA and ELISA are the most practical and reliable methods for detecting CMV antibodies. CMV-specific IgG avidity is low (mean 30%) when measured within the first 14 weeks after seroconversion, and it increases over time (mean 88% for patients with remote infections). This assay may be helpful in the diagnosis of primary CMV infection during pregnancy and may even be able to identify women who would deliver a CMV-infected infant (359,360). Rapid diagnosis of CMV infection is possible using antigen assays or molecular biological techniques such as the PCR (357). One needs to be aware that interlaboratory variability exists in the results of CMV PCR assays, especially for specimens containing lesser quantities of viral DNA (361). In a cohort of asymptomatic adolescents with primary CMV infection, CMV DNA was detected in buffy coat samples by PCR in 75% to 80% within 16 weeks of infection, and this declined to 0% to 25% after 48 weeks; lower recovery rates were noted in plasma specimens (362). Quantitation of CMV DNA in buffy coat, plasma, or serum is available, but this is mostly utilized in the management of immunosuppressed and organ transplant patients (357,363).

Several drugs are currently available for the treatment of CMV infection in the immunocompromised host, but they are almost never used in pregnant women (364,365,366). The drugs have a number of associated problems such as toxic side effects, poor oral bioavailability, and potential for emergence of drug-resistant virus strains (365). Ganciclovir, an acyclic nucleoside analogue of acyclovir, has excellent inhibitory activity against CMV (367). As with acyclovir, ganciclovir has to be phosphorylated initially by a viral enzyme. It is then eventually converted to the triphosphate form by cellular enzymes. Ganciclovir concentrations are at least ten-fold higher in CMV-infected cells than in uninfected cells (367). Ganciclovir is both mutagenic and teratogenic in pregnant experimental animals. The drug crosses the placenta into the fetal compartment passively without being metabolized (368,369). Valganciclovir is a prodrug of ganciclovir that is given orally (364). Foscarnet (phosphonoformate), another anti-CMV drug, inhibits the DNA polymerase of CMV. Like ganciclovir, foscarnet is used only in the immunosuppressed patient with CMV disease (367). Cidofovir is a nucleotide analogue that inhibits viral DNA polymerase. It has a long intracellular half-life, which allows its administration to adults once every 1 to 2 weeks. It is active against ganciclovir- or foscarnet-resistant CMV isolates. Its use currently is limited to immunocompromised adults, especially those with CMV retinitis (367,370).