The Effect of (Val)ganciclovir on Hearing in Congenital Cytomegalovirus: A Systematic Review

Abstract

Objective To search for existing evidence of a beneficial effect of (val)ganciclovir on hearing in children with congenital cytomegalovirus (cCMV) infection and to identify future research questions. Study Design Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, searches were performed in PUBMED, EMBASE, and WEB OF SCIENCE on December 15, 2021. Methods Studies providing ear‐specific hearing results after treating children with cCMV‐related hearing loss with (val)ganciclovir were retained. A meta‐analysis [Peto odds ratio (OR), Review Manager 5.3] was performed to compare hearing outcome between treated and untreated children. The National Institutes of Health tool was used for quality assessment and heterogeneity was assessed with I2 statistics. Results Eighteen studies with a total of 682 treated patients were included for the systematic review. Our meta‐analysis showed that treating symptomatic children with hearing loss resulted in more hearing improvement [Peto OR 7.72, 95% confidence interval (CI) 3.08–19.34] and less hearing deterioration (Peto OR 0.23, 95% CI 0.10–0.57). Relative to an improvement and deterioration rate of 9.4% and 28.2% in an untreated group, the rate of the treated group was 44.5% and 6.3%, respectively. Conclusions There is sufficient evidence in literature to support treatment with (val)ganciclovir of children with symptomatic cCMV and hearing loss. However, still today, there is insufficient evidence of the potential beneficial role of (val)ganciclovir on hearing outcome of children with isolated hearing loss, late‐onset hearing loss, and asymptomatic cCMV. The urgent need for future prospective, randomized clinical trials still exists. A standardization of definitions and treatment protocols would create uniformity in future studies. Laryngoscope, 132:2241–2250, 2022

Ophthalmic Complications, Diagnosis, and Treatment of Congenital Human Cytomegalovirus Infection

“…Worldwide literature reports cases of stabilization of local retinal conditions or resolution of choroidal and retinal inflammation after antiviral treatment with gancyclovir or valgancyclovir in infants with cCMV [ 31 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ]. However, authors of available studies on cCMV treatment often focus on complications other than ophthalmologic ones, primarily hearing disorders and the effectiveness of antiviral treatment in treating them [ 125 , 126 , 127 , 128 , 129 , 130 , 131 ]. Consequently, further studies involving a larger number of patients and employing detailed, targeted ophthalmologic diagnostics are necessary to determine the efficacy of antiviral therapy in the treatment of cCMV.…”

A Cross-Sectional Survey of Pediatric Infectious Disease Physicians’ Approach to Congenital Cytomegalovirus Infection

“…An NIH-funded, double-blind, placebo-controlled clinical trial (ValEAR) designed to determine the efficacy and safety of 6-month VGCV therapy in asymptomatic cCMV-infected infants 1–12 months of age with isolated SNHL (NCT03107871) was recently closed due to a lack of enrollment. A systematic review examining the existing evidence of VGCV on hearing in children with cCMV infection found insufficient evidence to support VGCV treatment of children with asymptomatic cCMV infection and isolated SNHL [ 28 ]. Future prospective randomized clinical trials to address this issue are needed.…”

The Audiological Follow-Up of Children with Symptomatic Congenital Cytomegalovirus Infection: An Experience in Two Italian Centers

“…Considering children with no other apparent lesions but hearing loss as symptomatic serves a functional purpose for several reasons: all cCMV infection cases must be followed independent of hearing thresholds, as hearing loss is the most frequent sequelae of cCMV infection and antiviral treatment can be initiated immediately by neonatologists after audiological evaluation. In this regard, a recent review reports that there is evidence in the literature to support antiviral treatment of children with symptomatic cCMV and hearing loss, but there is not the same evidence in relation to the potentially beneficial role of this on hearing outcome in children with isolate hearing loss [37]. A multidisciplinary approach to the treatment of all cCMV infection cases seems to be essential given the complexity of the health problems we are facing.…”