Association Between Expanded Genomic Sequencing Combined With Hearing Screening and Detection of Hearing Loss Among Newborns in a Neonatal Intensive Care Unit

Abstract

Key Points Question Is expanded genomic sequencing combined with hearing screening associated with the detection of hearing loss and the improvement in the clinical management of patients in the neonatal intensive care unit (NICU)? Findings In this cohort study that included 8078 patients in the NICU, expanded genomic sequencing was associated with a 15.6% increase in cases of diagnosed hearing loss that were missed by hearing screening and changed the clinical management strategies of these patients. Of 52 patients with a diagnosis of hearing loss, 39 (75%) had genetic findings and experienced a more severe degree of hearing loss. Meaning This study suggests that expanded genomic sequencing combined with hearing screening may be effective for diagnosing hearing loss in the NICU setting.

Comprehensive Genomic Sequencing–Based Screening for Hearing Loss in the Neonatal Intensive Care Setting—Is It Time?

“…However, such an approach is still challenging for population-based screening because it is relatively expensive, has an extended turnaround time spanning several weeks, and is associated with a significant burden of variant interpretation. Although these limitations were not addressed by Zhu et al, 1 their work implies that targeted genetic screening-using population-specific common pathogenic variants-combined with physiological and cytomegalovirus testing may be an effective newborn screening strategy for hearing loss, in critically ill neonates and beyond. This combinatory approach has the additional benefit of identifying mild and later-onset hearing loss and providing valuable genetic information that is often missed by traditional NHBS.…”

“…3 Thus, the PPV was 15.6% (5934 of 38 127 babies). With the use of the combined screening approach by Zhu et al, 1 the referral rate for those who had positive NBHS test results and/or positive genetic findings was 3.3% (265 of 8078). Of these babies, 240 were followed up, of whom 0.6% (52 of 8078) had confirmed hearing loss.…”

“…Zhu et al assessed the utility of combining expanded genomic sequencing with traditional physiological newborn hearing screening (NBHS) in the neonatal intensive care unit (NICU). The benefits associated with combining genetic and physiological screening, as illustrated by Zhu et al and elsewhere, include the identification of babies at risk for hearing loss who can benefit from early intervention yet are missed by NBHS, as well as genetic factors that may help improve the management of hearing loss in confirmed cases.…”

“…Zhu et al assessed the utility of combining expanded genomic sequencing with traditional physiological newborn hearing screening (NBHS) in the neonatal intensive care unit (NICU). The benefits associated with combining genetic and physiological screening, as illustrated by Zhu et al and elsewhere, include the identification of babies at risk for hearing loss who can benefit from early intervention yet are missed by NBHS, as well as genetic factors that may help improve the management of hearing loss in confirmed cases. In a cohort of 8078 patients admitted to the NICU, Zhu et al show that exome sequencing identified 7 patients with hearing loss who already had a negative NBHS test result (false negatives), thus increasing the total number of patients with confirmed hearing loss by 13.5% (7 of 52) in this setting.…”

“…The benefits associated with combining genetic and physiological screening, as illustrated by Zhu et al and elsewhere, include the identification of babies at risk for hearing loss who can benefit from early intervention yet are missed by NBHS, as well as genetic factors that may help improve the management of hearing loss in confirmed cases. In a cohort of 8078 patients admitted to the NICU, Zhu et al show that exome sequencing identified 7 patients with hearing loss who already had a negative NBHS test result (false negatives), thus increasing the total number of patients with confirmed hearing loss by 13.5% (7 of 52) in this setting. Furthermore, of all patients with confirmed hearing loss, 75.0% (39 of 52) had genetic findings, thus also providing important genetic information for a substantial proportion of patients.…”