CMV is a ubiquitous virus that may be transmitted in secretions, including saliva, tears, semen, urine, cervical secretions, blood (white blood cells), and breast milk. The seroprevalence increases with age and is influenced by many factors, such as hygienic circumstances, socioeconomic factors, breast-feeding, and sexual contacts. In addition to transplacental infection, CMV may also be transmitted to the infant intrapartum (through exposure to CMV in cervical secretions), via breast milk, and via blood transfusion of seropositive blood to an infant whose mother is seronegative. CMV infection acquired during delivery or via breast milk has no effect on future neurodevelopmental outcome in full-term infants. There is no definite evidence of CMV transmission among hospital personnel.
In developed countries, CMV seroprevalence varies inversely with socioeconomic status, with 40–80% of women of childbearing age in the United States having serologic evidence of past CMV infection. Seroconversion and initial infection can occur around the time of puberty, and shedding of the virus may continue for a long time. CMV can also become latent in white blood cells and reactivate periodically. In addition, a seropositive individual can be infected by a different strain of CMV.
Maternal reinfection by new strains of CMV has been recognized recently as a major source of congenital infection in a highly CMV-immune maternal population like that of Brazil. Reactivation and reinfection are grouped as a “nonprimary” infection. CMV is capable of penetrating the placental barrier as well as the blood–brain barrier. During early pregnancy, CMV has a teratogenic potential in the fetus. CMV infections may result in neuronal migration disturbances in the brain. Both primary and nonprimary maternal CMV infection can lead to transmission of the virus to the fetus. When primary maternal infection occurs during pregnancy, the virus is transmitted to the fetus in ∼35% of cases. Infection in early pregnancy causes more severe fetal infection with significant CNS sequelae. During nonprimary infection, transmission rate is only 0.2–1.8%. Even though the risk for congenital infection is high after primary maternal infection, nonprimary infection is responsible for 75% of the overall burden of congenital CMV infection.
More than 85% of infants born with CMV have a subclinical infection. Symptomatic infants are usually born to women with a primary infection. Symptomatic infants have a mortality rate of 20–30%. When the placenta becomes infected with CMV after a primary maternal infection, its ability to provide oxygen and nutrients to the developing fetus becomes impaired. This leads to placental enlargement due to viral placentitis and revascularization. Although not completely elucidated, placental tissue damage occurs due to direct tissue injury by persistent CMV replication, ischemic tissue damage due to vasculitis with viral infection of endothelial cells, and tissue damage by immune complex deposition. Eventual fetal viremia leads to fetal multiorgan involvement. The primary target organs are the CNS, eyes, liver, lungs, and kidneys.
Characteristic histopathologic features of CMV include focal necrosis, inflammatory response, formation of enlarged cells with intranuclear inclusions (cytomegalic cells), and the production of multinucleated giant cells. A sepsis-like illness has been described in premature infants.