Blood genome expression profiles in infants with congenital cytomegalovirus infection.

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.

Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection.

OBJECTIVE: To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination STUDY DESIGN: Retrospective, 2-center study (1996-2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination RESULTS: Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. CONCLUSION: Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.

A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening.

BACKGROUND AND OBJECTIVE: Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). METHODS: Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. RESULTS: Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. CONCLUSIONS: A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS.

The Parkland Memorial Hospital experience in ensuring compliance with Universal Newborn Hearing Screening follow-up.

OBJECTIVE: Reduce false-positive results and loss to follow-up through systematic modifications in Universal Newborn Hearing Screening at a large public hospital. STUDY DESIGN: During a pilot program, neonates who failed technician-performed automated auditory brain stem response were scheduled for diagnostic evaluation. In year 1, audiologists rescreened neonates who failed, and those who did not pass were screened as outpatients. For years 2 through 4, neonates who failed were rescreened by technicians before inpatient audiology rescreening. RESULTS: For the pilot, 3759 neonates were screened; 1% (n = 43) failed and 44% (n = 19) were lost to follow-up. In year 1, 15,297 neonates were screened and 2% (n = 365) failed; audiology rescreening reduced this to <1% (n = 129). Outpatient rescreening yielded 0.5% (n = 70) who failed; 17% (n = 12) were lost to follow-up. In year 2, 16,384 neonates were screened, 3% (n = 456) failed, and 1% (n = 167) failed after technician rescreen; audiology rescreening reduced inpatient fails to 0.6% (n = 108), and 0.4% (n = 61) failed outpatient rescreening; 11% (n = 7) were lost to follow-up. Results for years 3 and 4 were similar to year 2, with further reduction in loss to follow-up to 11% (n = 6) and 1.7% (n = 1). CONCLUSIONS: Successful Universal Newborn Hearing Screening with reduced false-positive results and loss to follow-up can be accomplished with a planned schedule of inpatient rescreens and outpatient rescreening at the birthing facility.