Analysis of archived newborn dried blood spots (DBS) identifies congenital cytomegalovirus as a major cause of unexplained pediatric sensorineural hearing loss

Abstract Purpose Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL). However, accurate diagnosis of cCMV as the etiology of SNHL is problematic beyond the neonatal period. This study therefore examined whether cCMV infection could be identified retrospectively in children presenting with unexplained SNHL to a multidisciplinary diagnostic outpatient otolaryngology clinic at an academic medical center in Minnesota. Methods Over a 4-year period, 57 patients with an age range of 3 months to 10 years with unexplained SNHL were recruited to participate in this study. Informed consent was obtained to test the archived dried blood spots (DBS) of these patients for cCMV infection by real-time PCR, targeting a highly conserved region of the CMV UL83 gene. Results were normalized to recovery of an NRAS gene control. Chart review was conducted to identify subjects who underwent genetic testing and/or neurodiagnostic imaging to investigate possible genetic, syndromic, or anatomical causes of SNHL. Results In total, 15 of the 57 children with unexplained SNHL tested positive for CMV DNA in their DBS (26%). A mean viral load of 8.3 × 10 4 (± 4.1 × 10 4 ) [range, 1 × 10 3 –6 × 10 5 ] copies/μg DNA was observed in subjects retrospectively diagnosed with cCMV. No statistically significant correlation was found between viral load and SNHL severity. Conclusions A retrospective DBS analysis demonstrated that 26% of patients presenting with unexplained SNHL in childhood had cCMV. DBS testing is useful in the retrospective diagnosis of cCMV, and may provide definitive diagnostic information about the etiology of SNHL.