LB17. Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

Abstract

BackgroundPrimary CMV infection during pregnancy carries a high risk of fetal transmission with the potential for severe sequelae. There is no universally accepted method of preventing congenital CMV. Our objective was to evaluate whether CMV hyperimmune globulin (HIG) administered to women with primary CMV during pregnancy reduces congenital infection.MethodsMulticenter randomized double-masked trial of women with a singleton gestation <24 weeks with primary CMV infection defined by the presence of either CMV IgM and IgG with low avidity or IgG seroconversion, as assessed at a central reference laboratory. Those with presumptive or confirmed evidence of fetal CMV were not eligible. Monthly infusions of HIG (100 units/kilogram) or placebo were given until delivery. The primary outcome was fetal loss or neonatal CMV infection defined as CMV by PCR or culture in urine or saliva within 3 weeks of birth, in amniotic fluid prior to delivery or in postmortem tissue. A sample size of 800 was planned to detect at least 30% reduction in the primary outcome with 90% power and type I error 5%.ResultsFrom 2012 to 2018, 206,111 pregnant women were screened; 712 (0.35%) had primary CMV infection; of whom, 399 (56%) were enrolled at 17 centers. The trial was stopped for futility at the recommendation of the Data and Safety Monitoring Committee due to a planned interim analysis that revealed complete enrollment was unlikely to demonstrate a significant outcome. Mean gestational age at randomization was 16.2 and 15.6 weeks in the HIG and placebo groups, respectively. Primary outcome data were available for 394 participants (98.7%). The primary outcome rate was 22.7% in the HIG group and 19.4% in the placebo group (relative risk [RR], 1.17; 95% confidence interval [CI], 0.80 to 1.72; p=0.42). Overall, there was no significant difference in the proportion of women with a side effect; however, those receiving HIG had a higher rate of headache (P = 0.05) and shaking chills (P = 0.03). The rate of preterm birth was 12.2% in the HIG group and 8.3% in the placebo group (RR, 1.47; CI 0.81 to 2.67; P = 0.2) (table). No statistical interactions were found in pre-specified subgroup analyses.ConclusionCMV HIG was not effective at decreasing risk of congenital CMV infection or fetal death among women with primary CMV infection in early pregnancy. Disclosures Brenna Hughes, MD, Merck (Consultant).