Newborn hearing screening: Will children with hearing loss caused by congenital cytomegalovirus infection be missed?

doi:10.1016/S0022-3476(99)70328-8

The Journal of Pediatrics

Volume 135, Issue 1, July 1999, Pages 60-64

https://doi.org/10.1016/S0022-3476(99)70328-8 Get rights and content

Abstract

Objective: To predict whether universal newborn auditory screening will identify most infants with sensorineural hearing loss (SNHL) caused by congenital cytomegalovirus (CMV) infection. Study design: A cohort of 388 children born between 1980 and 1996 at one hospital and identified during the newborn period as having congenital CMV infection received repeated hearing evaluations to assess whether hearing loss had occurred. Results: SNHL was detected in 5.2% of all infants at birth. Late-onset SNHL occurred among the children throughout the first 6 years of life. By the age of 72 months, the cumulative incidence of SNHL was 15.4% in the cohort. Children with clinically apparent disease at birth had significantly more SNHL than children without any apparent disease (22.8% vs 4.0% at 3 months and 36.4% vs 11.3% at 72 months of age). Conclusions: Universal screening of hearing in neonates will detect less than half of all SNHL caused by congenital CMV infection. Because most infants with congenital CMV infection are without symptoms at birth, these children are unlikely to be recognized as being at risk for SNHL and will not receive further hearing evaluations to detect late-onset hearing loss. A combined approach of universal screening of neonates for hearing, as well as for detection of congenital CMV infection, needs to be considered. (J Pediatr 1999;135:60-4)

Section snippets

Study Population

The study population includes children born between January 1, 1980, and December 31, 1996, who were identified by newborn screening for congenital CMV infection at one hospital in Birmingham, Alabama.² Congenital CMV infection was identified by isolation of the virus in urine or saliva in the first or second week of life.16, 17, 18 All children were assessed clinically for disease in the newborn period. Their medical records were systematically reviewed by study personnel to determine whether

RESULTS

The study population (Table I) was a predominantly black, urban population with the majority of infants showing no symptoms of congenital CMV infection at birth.

. Characteristics of study population of 388 children with congenital CMV infection

Characteristic	No.	%
Empty Cell	Children with congenital CMV infection
Race/Ethnicity
Black	337	86.9
White	50	12.9
Hispanic	1	0.2
Sex
Female	189	48.7
Male	199	51.3
Prenatal care
Private physicians	18	4.6
Health Department	358	92.3
None	12	3.1
Maternal age at delivery
<20 y	200	51.6
≥20 y	188	48.4
Marital

DISCUSSION

Our findings indicate only 5.2% of all infants with congenital CMV infection had hearing loss at birth and therefore would be identified by universal newborn hearing screening. Late-onset SNHL was identified in another 3.2% of children with CMV infection by 12 months of age and another 7% of the children by 72 months of age. Because delayed-onset SNHL followed congenital CMV infection, about two thirds of SNHL (>20 dB thresholds) caused by congenital CMV infection would not have been identified

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There are more references available in the full text version of this article.

Cited by (311)

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial
2024, Journal of Pediatrics
The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus–associated sensorineural hearing loss.
We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine.
Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome.
In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus–associated sensorineural hearing loss.
ClinicalTrials.gov identifier NCT01649869.
Importance of congenital cytomegalovirus in the neonatal hearing screening program
2023, Acta Otorrinolaringologica Espanola
En recién nacidos, la hipoacusia secundaria a una infección congénita por citomegalovirus (CMVc), pese a su baja prevalencia, puede generar un grave problema en el desarrollo personal y la integración social de los pacientes. Por ello, es importante incluir la determinación del ADN de CMV como herramienta del cribado neonatal.
Hemos realizado un estudio retrospectivo de 5 años, mediante la descripción de las CMVc en la Comunidad Autónoma del País Vasco en los recién nacidos que no superaron el cribado auditivo en el programa de detección precoz de hipoacusia. Se describen los tiempos de detección, confirmación (incidencia) e intervención (tratamiento).
De 18.782 sujetos estudiados, 58 (3 por cada 1.000 nacidos vivos) presentaron hipoacusia. De ellos, se confirmó CMVc en 4 pacientes (una mujer y 3 hombres).
El tiempo promedio para el cribado auditivo fue de 6,5 días (DE: ± 3,69) y para detectar el CMV mediante reacción en cadena de la polimerasa en orina y saliva fue de 4,2 días (DE: ± 3,94).
El tiempo para confirmar la hipoacusia mediante PEATC e intervención audiológica fue de 2,2 meses (DE: ± 0,957) y 5 meses (DE: ± 3,741), respectivamente.
Se realizaron 4 adaptaciones audioprotésicas y un implante coclear.
El cribado auditivo neonatal se ha consolidado como un buen programa de salud pública. La determinación del ADN viral permite un diagnóstico y tratamiento precoz, específico e interdisciplinar, en el que la otorrinolaringología tiene un papel fundamental. Nuestro estudio resalta la importancia de incluir la reacción en cadena de la polimerasa del CMV como herramienta de cribado universal.
In newborns, hearing loss secondary to congenital cytomegalovirus (CMVc) infection, despite its low prevalence, can cause a serious problem in the personal development and social integration of patients. Therefore, it is important to include the determination of CMV DNA as a neonatal screening tool.
We have carried out a 5-year retrospective study, by describing the CMVc in the Autonomous Community of the Basque Country (Spain) in newborns who did not pass the hearing screening in the early hearing loss detection program. The times of detection, confirmation (incidence) and intervention (treatment) are described.
Of 18,782 subjects studied, 58 (3 per 1,000 live births) presented hearing loss. Of these, CMVc is guaranteed in 4 patients (one woman and 3 men). The mean time to hearing screening was 6.5 days (SD: ±3.69) and to detect CMV by polymerase chain reaction in urine and saliva was 4.2 days (SD: ±3.94). Time to confirm hearing loss by BAEP and audiological intervention 2.2 (SD: ±0.957) and 5 months (SD: ±3.741), respectively. Four hearing aid adaptations and one cochlear implant were performed.
Neonatal hearing screening has established itself as a good public health program. The determination of viral DNA allows an early, specific and interdisciplinary diagnosis and treatment, in which otorhinolaryngology plays a fundamental role. Our study highlights the importance of including CMV polymerase chain reaction as a universal screening tool.
The cost-effectiveness of targeted screening for congenital cytomegalovirus in newborns compared to clinical diagnosis in the US
2023, International Journal of Pediatric Otorhinolaryngology
Congenital cytomegalovirus (cCMV) is the leading environmental cause of hearing loss (HL) among children, affecting four in one thousand newborns. cCMV testing in the US is currently based on clinical diagnosis which does not consistently identify cCMV cases and precludes early intervention to prevent and reduce the severity of HL. We estimated the cost-effectiveness of targeted newborn screening and cCMV testing among newborns compared to clinical diagnosis.
We use a decision-analytic model to estimate the costs of preventing HL progression, of additional cases of severe HL, of identifying a case of HL one year earlier, and of identifying an additional case of cCMV, through targeted screening and cCMV testing for infants failing two newborn hearing screens with follow-up to age five. We also estimate the costs of nationwide implementation of a newborn screening and testing program. Model pathways were based on best practices for screening, testing, and treatment. Probabilities were drawn from the published literature; costs were estimated based on Medicare reimbursement rates. Probabilistic and scenario analyses were conducted to determine the robustness of results.
Targeted testing and cCMV screening, compared to standard of care, cost an additional $2.96 (±2.26) per infant screened and identified 0.00038 (±0.00022) cases of HL, 3.8 in 10000 children, at a cost of $8197 (±4217) per case of HL identified. Implementing targeted screening for all children in the US was estimated to cost $193,229.
Although cases numbers are small, our model shows that targeted newborn screening and cCMV testing reduced cases of HL progression. Adoption of newborn targeted screening as standard of care should be considered given it may prevent disability at very low cost.
Congenital Sensorineural Hearing Loss
2022, Pediatric Clinics of North America
Hearing loss caused by CMV infection is correlated with reduced endocochlear potentials caused by strial damage in murine models
2022, Hearing Research
Congenital cytomegalovirus (CMV) infection is a significant cause of neonatal hearing loss. However, at the cochlear level, the anatomical lesions and pathophysiological mechanisms that underlie hearing loss are still not clearly understood. In murine models of CMV infection, we have observed early damage to the capillary networks in stria vascularis, as well as hearing loss manifested in ABR threshold elevations. Our experimental hypothesis is that strial damage causes a reduced endocochlear potential (EP) resulting in impaired haircell activation and consequent hearing loss. We have studied strial damage, EP, and ABR threshold elevations in two mouse models (BALB/c and C57BL6 strains) infected with murine CMV. Neonatal (P3) pups were inoculated with murine CMV (2µl of 200pfu) by intra cerebral injection. Control mice were saline injected. At 6 weeks, ABR thresholds to tonal stimuli at 8, 16 and 32 kHz were determined for each ear. At 8 weeks a sub-group of treated and control animals was prepared for study of cochlear capillary networks using scanning electron microscopy of corrosion cast specimens. In a second group, at 8 weeks, EP measurements from both cochleas were made. We report that in both mouse strains, CMV infection caused capillary loss in the stria vascularis, initially at the cochlear apex, and extending to lower cochlear turns in some subjects. After CMV infection, in both BALB/c and C57BL6 mice, reduced EPs and ABR threshold elevations were observed, and there was a within-animal correlation between loss of EP and ABR threshold elevations across the sound frequencies tested. These results suggest that CMV induced damage to stria vascularis results in EP reduction that is correlated with ABR threshold elevations. Extrapolating to the human condition, we suggest that strial damage and its physiological consequences may contribute to the initial hearing loss in congenital CMV infection. The early involvement of cochlear capillary damage may encourage a focus on therapeutic interventions that can prevent vascular damage, or subsequently promote vascular healing or angiogenesis.
Vestibular and postural impairment in congenital Cytomegalovirus infection
2022, International Journal of Pediatric Otorhinolaryngology
To describe the vestibular and postural impairment related to the congenital Cytomegalovirus infection (cCMV), including the inner ear damages CMV-induced.
A PRISMA systematic review was performed, with the PubMed, Embase, and Cinahl databases searched from inception through to March 2021; after the application of inclusion and exclusion criteria a total of 12 papers were included in this review.
Vestibular and postural disorders have been reported in cCMV children, with a high variability of clinical manifestation. Presently, the available reported data on vestibular and postural impairment in cCMV children differ in terms of the sample size and the features of the studied populations.
At present, the vestibular and postural impairment in cCMV cases is underestimated; a complete vestibular assessment, a follow-up and management of all children affected by cCMV or, at least, of all cCMV patients showing sensorineural hearing loss, is recommended.

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^☆: Supported in part by research grant number 5 P01 HD 10699 from the National Institute of Child Health and Human Development, research grant number 5 R01 DC 02139 from the National Institute on Deafness and Other Communication Disorders, research grant number 5 M01 RR 00032 from the General Clinical Research Center, National Institutes of Health and the Civitan International Research Center.

^☆☆: Reprint requests: Karen B. Fowler, DrPH, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Ave South, Suite 752, Birmingham, AL 35233.

^★: 0022-3476/99/$8.00 + 0 9/21/99423

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Newborn hearing screening: Will children with hearing loss caused by congenital cytomegalovirus infection be missed?☆,☆☆,★

Abstract

Section snippets

Study Population

RESULTS

DISCUSSION

J Pediatr

J Pediatr

J Pediatr

Summary of a workshop on surveillance for congenital cytomegalovirus disease

Rev Infect Dis

Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990

J Infect Dis

Outcome of symptomatic congenital CMV infection: results of long-term longitudinal follow-up

Pediatrics

Symptomatic congenital cytomegalovirus: disorders of language, learning and hearing

Am J Dis Child

Clinical importance of cytomegalovirus infection: an overview

Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection

Pediatrics

School failure and deafness after “silent” congenital cytomegalovirus infection

N Engl J Med