Congenital Human Cytomegalovirus Infection Is Associated With Decreased Transplacental IgG Transfer Efficiency Due to Maternal Hypergammaglobulinemia

Abstract Background Placentally transferred maternal immunoglobulin G (IgG) protects against pathogens in early life, yet vertically transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored. Methods We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a US-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive nontransmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year. Results Transplacental IgG transfer efficiency was decreased by 23% (95% confidence interval [CI] 10–36%, P = .0079) in cCMV-infected pairs and 75% of this effect (95% CI 28–174%, P = .0085) was mediated by elevated maternal IgG levels (ie, hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection. Conclusions Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer. We evaluated transplacental IgG transfer in a case-control cohort of mother-infant pairs with and without congenital human cytomegalovirus (cCMV) infection. Transplacental immunoglobulin G (IgG) transfer efficiency was reduced in pairs with cCMV infection, primarily attributable to maternal hypergammaglobulinemia in HCMV-transmitting mothers.