Human cytomegalovirus (HCMV) is the most common vertically transmitted infectious agent and occurs in the United States with an estimated prevalence of 0.65%[1]. The birth prevalence of congenital CMV (cCMV) is higher in developing countries [2] than in developed countries. Although most CMV-infected newborns are asymptomatic, cCMV can be a major cause of neurodevelopmental delay and infant brain damage and is the leading cause of nongenetic sensorineural hearing loss worldwide [3, 4]. The risk of transplacental transmission is highest (upwards of 40%) in the setting of a primary maternal infection during pregnancy, and the greatest risk of sequelae is associated with fetal infections that occur during the first trimester [5]. Although fetal infections occurring later in pregnancy are less likely to cause sequelae, some experts have recommended that all infants with cCMV should undergo routine audiologic and neurodevelopmental screening assessment [6].

Most women have no symptoms associated with the acquisition of HCMV infection during pregnancy, and routine screening of women for HCMV antibodies is not typically performed by obstetricians. Thus, the precise timing of both maternal and fetal infection is very difficult to ascertain. There is interest in offering therapeutic interventions to women, particularly in the setting of documented first-trimester HCMV infections, toward the goal of minimizing the risk of adverse sequelae for the infected fetus. Because of the recognized importance of virus-neutralizing antibodies in convalescence and control of HCMV infection, and the beneficial effect of therapeutic HCMV hyperimmune globulin (HIG) in control of disease in immunosuppressed transplant patients [7], studies were commenced approximately 20 years ago to examine whether HIG could modify the risk of fetal infection and/or disease if administered to a pregnant woman with a primary HCMV infection. What has followed over the years is a saga of seemingly conflicting reports with very different conclusions. In an early study conducted by Nigro and colleagues [8], women whose amniotic fluid contained either HCMV or HCMV DNA (indicating that fetal infection was already present) were offered intravenous HIG at a dose of 200 U per kilogram of maternal weight (treatment