Hearing Loss in Congenital CMV Disease Post-Ganciclovir

Abstract

Source: Lanzieri TM, Caviness AC, Blum P, et al. Progressive, long-term hearing loss in congenital CMV disease after ganciclovir therapy. J Pediatric Infect Dis Soc. 2021;piab095. doi:10.1093/jpids/piab095Investigators from the CDC, Atlanta, GA, and Baylor College of Medicine, Houston, TX, conducted a study to assess long-term hearing outcomes in children with symptomatic congenital cytomegalovirus (CMV) infection, and the impact of ganciclovir therapy on hearing loss. For the study, they analyzed data from children born 1983–2005 who were enrolled in the Congenital CMV Longitudinal Study. All study participants had CMV infection detected in urine samples in the first 3 weeks of life and had microcephaly, chorioretinitis, neurologic abnormalities or evidence of reticuloendothelial system involvement (eg, petechiae/purpura). Study children had longitudinal assessments of hearing with auditory brainstem response testing and behavioral audiometry; those with hearing thresholds >20 dB were classified as having sensorineural hearing loss (SNHL). SNHL was defined as congenital if diagnosed in the first month of life. Study children were placed into 3 groups: Group A included patients who had been enrolled in a clinical trial and received ganciclovir; group B included children with SNHL, microcephaly and/or chorioretinitis but who were untreated; and group C comprised those without any of these findings who also were not treated with ganciclovir. The primary study outcome was long-term assessment of hearing loss among children in these 3 groups.Data were analyzed on 76 children; 17 (22%) in group A, 27 (36%) in group B, and 32 (42%) in group C. Among the 17 children in group A, 16 had microcephaly, chorioretinitis, or congenital SNHL; median duration of ganciclovir treatment in these patients was 40 days. Overall, the most common findings in study patients when they were neonates were purpura/petechiae (82% of those in group A, 78% in group B, and 63% in group C); 71% and 70%, respectively, of those in groups A and B had microcephaly. Congenital SNHL was diagnosed in 65% of patients in group A and 56% for those in group B, although hearing was not assessed in the first month of life in all study participants. The median age at last hearing assessment was 13 years for children in groups A and C and 11 years for those in group B. At that time, 16 (94%) patients in group A, 24 (89%) children in group B, and 16 (50%) group C patients had SNHL. SNHL was categorized as severe (>70 dB) in 12 (71%), 16 (59%), and 7 (22%) children, respectively, in groups A, B, and C.The authors conclude that most children in this study with congenital CMV infection developed substantial SNHL with or without ganciclovir treatment.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current investigators provide long-term hearing outcomes for infants born 1983–2005 who were enrolled in the Congenital CMV Longitudinal Study. Participants were selected based on having severe disease as newborns.1,2 Not surprisingly, most developed substantial SNHL. As previously discussed, symptomatic congenital CMV infection at birth is a risk factor for SNHL. (See AAP Grand Rounds. 2019;42[5]:57.)3 Many infants also had microcephaly and/or head CT scan findings suggesting tissue destruction or dysplastic growth, which also are associated with an increased risk of SNHL.4 The results of early clinical trials of intravenous ganciclovir1,2 had suggested short-term stabilization or improvement in hearing at 6 months but were not borne out by the current investigation.With the introduction of oral valganciclovir, a phase III, randomized, placebo-controlled clinical trial, conducted during 2008– 2011, evaluated 6 weeks versus 6 months of therapy with valganciclovir.5 There was modest improvement in hearing and developmental outcomes at 12 and 24 months. Based on this trial, the AAP currently recommends 6 months of oral valganciclovir for infants with moderately to severely symptomatic congenital CMV infection who can start treatment in the first month of life.6 The current authors state that their findings cannot be extrapolated to infants who receive current standard of care therapy. Infants receiving valganciclovir are being followed to determine their long-term hearing outcomes.Another area that is not addressed is the role of valganciclovir for infants with congenital CMV infection who have isolated SNHL. The 2017 consensus guidelines do not routinely recommend valganciclovir for these infants based on insufficient evidence. Pasternak et al reported that 12 months of antiviral therapy for infants with congenital CMV infection and isolated SNHL led to improved hearing, but their study did not include a control group.(See AAP Grand Rounds. 2018;40[5]:55.)8Infants with congenital CMV infection are at risk for SNHL despite receipt of antiviral therapy. These infants deserve close audiology follow-up.The apparent lack of major benefit of antiviral therapy in children with symptomatic congenital CMV infection underscores the need for prevention. Neither CMV-IGIV nor investigational vaccines have yet proven efficacious.6