Prognostic Factors of Late-onset Hearing Loss in Infants With Congenital Cytomegalovirus and Normal Audiologic Assessment at Birth

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BACKGROUND: Children with congenital cytomegalovirus (cCMV) can develop late-onset sensorineural hearing loss (LO-SNHL). In this study, we aim to assess the characteristics and predictors of LO-SNHL in infants with cCMV having normal hearing at the first neonatal assessment. METHODS: A retrospective study within the European Registry of Children with cCMV ( www.ccmvnet.org ) was performed. Included children had cCMV and a normal first audiological assessment by Auditory Brainstem Response (ABR). Late-onset hearing loss (LO-SNHL) is defined as the presence of sensorineural hearing loss after an initial normal hearing test. Hearing evaluation was performed at birth, at 6 months of age, and at least annually up to 6 years of age. RESULTS: Seven hundred twenty-one children with normal audiological tests at birth were included, and 47/721 (6.5%) developed LO-SNHL. LO-SNHL was diagnosed at a range of 4-65 months of age [median (IQR) age: 34.3 (15.1-48.7) months]. Children with LO-SNHL had a higher proportion of abnormalities on physical examination at birth (45.7% vs. 20.8%; P < 0.001): petechiae (17.4% vs. 6.0%; P = 0.008), splenomegaly (8.7% vs. 2.3%; P = 0.031), hepatomegaly (13% vs. 2.9%; P = 0.001), microcephaly (15.2% vs. 4.5%; P = 0.005) and small for gestational age (21.7% vs. 8.3% P = 0.005). Children with LO-SNHL showed lower platelet count at birth [177500.0 (88750.0-261250.0)/μL vs. 243500.0 (173000.0-304000.0)/μL; P = 0.012], and higher blood viral load at birth [3.7 log (3.3-4.4) vs. 3.4 log (2.7-3.9) IU/mL; P = 0.013] and had more frequent white matter involvement (27.7% vs. 14.7%; P = 0.03) and ventriculomegaly (20.7% vs. 4.6%; P = 0.001) on birth magnetic resonance imaging. Overall, symptomatic children at birth showed a higher risk of developing LO-SNHL than asymptomatic children (32/317, 10.1%, vs. 15/404, 3.7%; P < 0.0001). Among asymptomatic children, only 0.3% developed severe or profound LO-SNHL in the best ear.In multivariate logistic regression analysis, ventriculomegaly [odds ratio (OR): 7.503 (1.78-27.9)], white matter abnormalities [OR: 3.19 (1.010-9.01)], and splenomegaly [OR: 3.679 (1.56-8.506)] at birth were associated with the development of LO-SNHL ( Fig. 1 ). CONCLUSIONS: Among this large cohort of children with cCMV and a first normal audiological assessment, the risk of LO-SNHL was 6.5%. Asymptomatic children developed LO-SNHL in 3.7% of the cases versus 10.1% in symptomatic cases. In multivariate logistic regression analysis, ventriculomegaly, white matter abnormality, and splenomegaly at birth were associated with LO-SNHL.

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