Dataset Information

Hearing Trajectory in Children with Congenital Cytomegalovirus Infection.

ABSTRACT: Objectives To compare hearing trajectories among children with symptomatic and asymptomatic congenital cytomegalovirus infection through age 18 years and to identify brain abnormalities associated with sensorineural hearing loss (SNHL) in asymptomatic case patients. Study Design Longitudinal prospective cohort study. Setting Tertiary medical center. Subjects and Methods The study included 96 case patients (4 symptomatic and 92 asymptomatic) identified through hospital-based newborn cytomegalovirus screening from 1982 to 1992 and 72 symptomatic case patients identified through referrals from 1993 to 2005. We used growth curve modeling to analyze hearing thresholds (0.5-8 kHz) by ear with increasing age and Cox regression to determine abnormal findings on head computed tomography scan associated with SNHL (hearing threshold ?25 dB in any audiometric frequency) among asymptomatic case patients. Results Fifty-six (74%) symptomatic and 20 (22%) asymptomatic case patients had SNHL: congenital/early-onset SNHL was diagnosed in 78 (51%) and 10 (5%) ears, respectively, and delayed-onset SNHL in 25 (17%) and 20 (11%) ears; 49 (32%) and 154 (84%) ears had normal hearing. In affected ears, all frequency-specific hearing thresholds worsened with age. Congenital/early-onset SNHL was significantly worse (severe-profound range, >70 dB) than delayed-onset SNHL (mild-moderate range, 26-55 db). Frequency-specific hearing thresholds were significantly different between symptomatic and asymptomatic case patients at 0.5 to 1 kHz but not at higher frequencies (2-8 kHz). Among asymptomatic case patients, white matter lucency was significantly associated with SNHL by age 5 years (hazard ratio, 4.4; 95% CI, 1.3-15.6). Conclusion Congenital/early-onset SNHL frequently resulted in severe to profound loss in symptomatic and asymptomatic case patients. White matter lucency in asymptomatic case patients was significantly associated with SNHL by age 5 years.

SUBMITTER: Lanzieri TM

PROVIDER: S-EPMC5880689 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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Hearing Trajectory in Children with Congenital Cytomegalovirus Infection.

Lanzieri Tatiana M TM Chung Winnie W Leung Jessica J Caviness A Chantal AC Baumgardner Jason L JL Blum Peggy P Bialek Stephanie R SR Demmler-Harrison Gail G

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 20180320 4

Objectives To compare hearing trajectories among children with symptomatic and asymptomatic congenital cytomegalovirus infection through age 18 years and to identify brain abnormalities associated with sensorineural hearing loss (SNHL) in asymptomatic case patients. Study Design Longitudinal prospective cohort study. Setting Tertiary medical center. Subjects and Methods The study included 96 case patients (4 symptomatic and 92 asymptomatic) identified through hospital-based newborn cytomegalovir ...[more]

PMID: 29557247

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Project description:In developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps such as hearing loss, requiring extensive follow-up. However, early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfaction might represent a valuable prognosis for neurological outcome of this viral infection. Here, we demonstrate that in utero CMV inoculation causes fetal infection and growth retardation in mice of both sexes. It disrupts OB normal development, leading to disproportionate OB cell layers and rapid major olfactory deficits. Olfaction is impaired as early as day 6 after birth in both sexes, long before the emergence of auditory deficits. Olfactometry in males reveals a long-lasting alteration in olfactory perception and discrimination, particularly in binary mixtures of monomolecular odorants. Although sensory inputs to the OB remain unchanged, hallmarks of autophagy are increased in the OB of 3-postnatal week-old mice, leading to local neuroinflammation and loss of neurons expressing tyrosine hydroxylase and calbindin. At the cellular level, we found CMV-infected cells and an increased number of apoptotic cells scattered throughout the OB layers, whereas cell proliferation in the neurogenic subventricular zone was decreased. These cellular observations were long-lasting, persisting up to 16 weeks after birth in both males and females and thus providing a mechanism supporting olfactory loss. Despite obvious differences in neurogenesis between human and mouse, these findings offer new strategies aimed at early detection of neurological dysfunctions caused by congenital infections.SIGNIFICANCE STATEMENT In developed countries, congenital cytomegalovirus (CMV)-infected newborns are at high risk of developing sensory handicaps such as hearing loss, thus requiring prolonged follow-up. In this study, we describe for the first time the functional impact of congenital CMV infection on the olfactory system and its associated sense of smell. We demonstrate that a mouse model of congenital CMV infection shows defects in olfactory bulb (OB) normal development and pronounced olfactory deficits affecting acuity and discrimination of odorants. These major olfactory deficits occur long before the emergence of auditory deficits through the upregulation of OB autophagy inducing local neuroinflammation and altered neuron content. Our findings provide new opportunities for designing olfactory means to monitor the possible neurological outcome during congenital CMV infection.

Dataset Information

Hearing Trajectory in Children with Congenital Cytomegalovirus Infection.

Publications

Hearing Trajectory in Children with Congenital Cytomegalovirus Infection.

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