BACKGROUND: The pathogenesis of cytomegalovirus (CMV)-related hearing loss is not well understood. OBJECTIVE: To evaluate the relationship between persistent CMV shedding and delayed sensorineural hearing loss in children born with congenital CMV. METHODS: Serial audiologic assessments and CMV cultures of urine and saliva were performed on 580 children who had been diagnosed with congenital CMV infection. RESULTS: Prevalence of CMV culture-positivity in any specimen decreased to approximately 50% by the third birthday and approximately 5% after the seventh birthday. Intermittent shedding occurred in 28% of children. Seventy-seven children had hearing loss at birth and 38 children developed delayed hearing loss by the end of follow-up. In multivariate analyses, delayed hearing loss was strongly associated with symptomatic infection at birth (OR = 5.9, 95% CI: 1.8-18.9) and modestly associated with older age at last culture-positive visit (OR = 1.6, 95% CI: 1.1-2.0, comparing 1-year age differences) Observed rates of delayed hearing loss were 0.79 per 100 person-years for children asymptomatic at birth and 4.29 per 100 person-years for children symptomatic at birth. Between the ages of 6 months and 8 years, we would expect delayed hearing loss to occur in 6.9% of asymptomatic children and in 33.7% of symptomatic children. CONCLUSIONS: The strongest risk factor for delayed hearing loss was CMV-related symptoms at birth, but many asymptomatic children also developed delayed hearing loss. Longer duration of CMV shedding may also be a predictor of delayed hearing loss. © 2009 by Lippincott Williams & Wilkins.