Cytomegalovirus (CMV) infection during pregnancy carries with it a high risk that the fetus will die, be born prematurely, or have hearing loss and developmental delays. A method of preventing congenital infection is needed, but results of a randomized trial presented at the 46th Annual Meeting of the Infectious Diseases Society for Obstetrics and Gynecology (IDSOG) suggest that CMV hyperimmune globulin (HIG) is not the answer.
Researchers from the Eunice Kennedy Shrivers National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network conducted the trial at 17 centers to determine whether CMV HIG would reduce fetal loss or neonatal CMV infection. The multicenter, randomized, double-masked trial had a planned sample size of 800 women with a singleton gestation < 24 weeks’ gestation who had primary CMV infection, as defined by presence of either serum CMV IgM and IgG with low avidity or IgG seroconversion. At that size, it had 90% power to detect at least 30% reduction in the primary outcome, which was fetal loss or neonatal CMV infection defined as CMV by polymerase chain reaction or culture in urine or saliva within 3 wees of birth, in amniotic fluid prior to delivery or in postmortem tissue.
Between 2012 and 2018, more than 200,000 women were screened, of whom 399 ultimately were enrolled. Randomization was to monthly infusions of HIG (100 units/kg) or placebo until delivery, and mean gestational age at the time of randomization was 16.2 and 15.6 weeks in the HIG and placebo groups, respectively.
At interim analysis, the trial was stopped for futility on the recommendation of the Data and Safety Monitoring Committee because of a finding that complete enrollment was statistically very unlikely to demonstrate a significant difference between the groups. Of the 394 women for whom data were available, 22.7% in the HIG group met the primary outcome versus 19.4% in the placebo group (relative risk [RR] 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Rates of preterm birth were 12.2% in the HIG group versus 8.3% in the placebo group (RR 1.47; CI 0.81 to 2.67; P = 0.2). Rates of side effects in the two groups were not significantly different.
The authors concluded that CMV HIG “is not effective at decreasing the risk of congenital CMV infection or fetal death among women with primary CMV infection in early pregnancy.”