Congenital Cytomegalovirus Is the Second Most Frequent Cause of Bilateral Hearing Loss in Young French Children

Abstract

In children with congenital cytomegalovirus (cCMV), greater than 50% of symptomatic newborns and 8.5% to 18% of asymptomatic newborns will have hearing loss, either present at birth or delayed in onset. This prospective study was undertaken to evaluate the extent of cCMV among causes of hearing loss in French children younger than 3 years and to assess their characteristics in relation to cCMV status. Children younger than 3 years with hearing loss were prospectively enrolled. Cytomegalovirus polymerase chain reaction (PCR) assays were performed on dried blood spots from these children’s Guthrie cards and considered positive when CMV presence was confirmed. Brain computed tomography (CT) or magnetic resonance imaging and temporal bone CT scans were obtained. Normal hearing, mild loss, moderate loss, severe loss, and profound loss were defined when the child was able to hear a stimulus of 0 to 20, 21 to 40, 41 to 70, 71 to 90, and 91 dB or greater, respectively. Results of genetic analysis of the connexin 26 (GJB2) and connexin 30 (GJB2) genes were recorded. The prevalence of cCMV infection was estimated together with its 95% confidence interval. Of 114 eligible children, 100 with bilateral hearing loss were enrolled at a median age of 15 months and included in the analysis. Hearing loss in the best ear was not recorded for 2 children and was mild in 1 child, moderate in 22 children, severe in 16, and profound in 59. Results of brain and temporal bone imaging were available for 77 children and genetic analysis of the GJB2 and GJB2 genes for 55 children. Cytomegalovirus PCR was positive in 8 children, and cCMV infection prevalence was 8.0% (95% confidence interval, 2.7%–13.3%). Prevalence of cCMV was 13.7% (n = 8) in the 59 children with profound bilateral hearing loss, a significant association (P = 0.02). Children with cCMV were significantly more likely to have delayed development (P = 0.027) and abnormalities on the brain CT scan (P = 0.0005). Two of the 8 children with cCMV had at least 1 other risk factor for hearing loss, including neonatal intensive care unit stays or familial history of hearing loss. None of the 8 children with cCMV were born prematurely, but 4 had a small birth weight for their gestational age, and 1 child had microcephaly. In 2 children, the diagnosis of cCMV infection had been made before inclusion in the study. For the other 6 children, the diagnosis of cCMV was made retrospectively because of the positive CMV PCR result. In 61 patients (71.8%), the origin of hearing loss was genetic. Mutations of GJB2 and/or GJB2 genes were found in 22 patients (25.9%). In 1 patient (1.2%), hearing loss was due to a mutation in the otoferlin gene. In 13 patients (15.3%), a syndromic origin included Waardenburg syndrome, Usher syndrome, Angelman disease, mucopolysaccharidosis, and another metabolic disease. In 8 patients (9.4%), a malformation was found in the temporal bone on CT scan that was considered genetic. A genetic origin also was highly probable in 10 with a history of 1 family member with hearing loss before age 40 years and consanguineous parents in 7. Prematurity was the cause of hearing loss in 6 children (7.1%). Congenital CMV was present in 8 (9.4%) of the 85 patients with a complete workup and was the second most common individual cause of bilateral hearing loss after connexin mutations. The prevalence of cCMV indicates only the proportion of cCMV among French children with bilateral hearing loss and not the prevalence of cCMV in the total population of children with hearing loss. Because universal neonatal hearing screening is underway in France, it may be possible to diagnose cCMV in infants with confirmed hearing loss and to implement early intervention with antiviral treatment.