Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection

Abstract

Approximately 1% of all newborn infants reportedly have congenital cytomegalovirus (CMV) infection. The disorder is symptomatic in approximately one in 10 infants, and clinically significant neurologic sequelae develop in nearly half of them. Neurologic defects eventually develop in as many as 13% of newborn infants who lack symptoms. This prospective study evaluated hyperimmune globulin for treating or preventing fetal CMV infection. Participants were pregnant women with primary CMV infection. Women with primary infection for longer than 6 weeks were offered amniocentesis and treatment with 200 U/kg of intravenous hyperimmune globulin if CMV DNA was identified in amniotic fluid. If necessary, subsequent doses of 400 U/kg were given intravenously or into the umbilical cord or amniotic fluid. Women who declined amniocentesis were offered preventive treatment (100 U/kg of hyperimmune globulin per month). Untreated women served as control subjects. Of women with documented fetal infection, only one of 31 given hyperimmune globulin delivered an infant with CMV disease compared with 7 of 14 untreated women. On logistic regression analysis, treatment significantly lowered the risk of congenital disease. For prevention of fetal infection, 37 women received monthly infusions of hyperimmune globulin 2 to 11 weeks after presumed maternal seroconversion. Of these, 6 (16%) delivered an infected infant compared with 19 of 47 (40%) of untreated women. Treatment was the only factor that predicted a significant reduction in the risk of congenital infection. Treatment, whether therapeutic or preventive, correlated significantly with increased titers of CMV-specific immunoglobulin G. The percentage of total natural killer cells was significantly less in women receiving hyperimmune globulin. No adverse events were observed. Intravenous treatment with CMV-specific hyperimmune globulin is safe and may be effective both in preventing congenital infection and treating established infection.