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Departments of aOtorhinolaryngology, Head and Neck Surgery, and Communication Disorders and bMedical Genetics, University of Antwerp, Anwerp, Belgium
The authors have indicated they have no financial relationships relevant to this article to disclose.
Hearing loss is one of the most common congenital anomalies. Hearing impairment in To the best of our knowledge, this is the first report in the literature that provides data on
infants can negatively affect speech and language acquisition, academic achievement, both audiologic confirmation and etiologic assessment in a large sample of newborns
and social and emotional development. These negative effects can be diminished referred after failed screening.
through early intervention.
ABSTRACT
OBJECTIVE. The goal was to clarify the audiologic aspects and causes of congenital
hearing loss in children who failed universal neonatal hearing screening.
www.pediatrics.org/cgi/doi/10.1542/
METHODS. A prospective analysis of 170 consecutive records of neonates referred to a peds.2007-1479
tertiary center after universal neonatal hearing screening failure, between 1998 and doi:10.1542/peds.2007-1479
2006, was performed. The data presented here represent the equivalent of ⬃87 000 Key Words
screened newborns. The screening results were validated with a clinical ear, nose, congenital sensorineural hearing loss,
and throat examination and electrophysiological testing, including diagnostic audi- cytomegalovirus, genetics, hearing
screening, newborn
tory brainstem response, automated steady state response, and/or behavioral testing.
A diagnostic evaluation protocol for identification of the cause of the hearing loss was Abbreviations
UNHS— universal neonatal hearing
also implemented, in collaboration with the departments of genetics and pediatrics. screening
ABR—auditory brainstem response
RESULTS. Permanent hearing loss was confirmed in 116 children (68.2%). Bilateral AABR—automated auditory brainstem
hearing loss was diagnosed in 68 infants (58.6%) and unilateral hearing loss in 48 response
infants (41.4%). Median thresholds for the neonates with confirmed hearing loss PCR—polymerase chain reaction
CMV— cytomegalovirus
were severe in both unilateral and bilateral cases, at 70 dB nHL and 80 dB nHL, WS—Waardenburg syndrome
respectively. In 55.8% of those cases, no risk factors for hearing loss were found. In Accepted for publication Sep 27, 2007
60.4%, the initial automated auditory brainstem response diagnosis was totally in Address correspondence to Frank Declau, MD,
agreement with the audiologic evaluation results. In 8.3% of the cases, however, a PhD, Department of Otorhinolaryngology,
unilateral refer result was finally classified as bilateral hearing loss. An etiologic factor Head and Neck Surgery, and Communication
Disorders, University Hospital Antwerp,
could be identified in 55.2% of the cases. Of the causes identified, a genetic mech- Wilrijkstraat 10, B-2650 Edegem, Belgium.
anism was present in 60.4% of the cases, peripartal problems in 20.8%, and con- E-mail: nko@telenet.be
genital cytomegalovirus infection in 18.8%. PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright © 2008 by the
CONCLUSIONS. An etiologic factor could be identified for nearly one half of the children American Academy of Pediatrics
with confirmed congenital hearing loss referred through a universal hearing screen-
ing program. Pediatrics 2008;121:1119–1126
H EARING LOSS IS one of the most common congenital anomalies, occurring in ⬃1 to 2 infants per 1000.1 The
prevalence of hearing loss has been shown to be greater than that of most other diseases and syndromes
screened for at birth (eg, phenylketonuria and sickle cell disease). The incidence of hearing loss is considerably higher
in infants in the NICU (1–2 cases per 200 infants; 1.9% bilateral and 0.6% unilateral.2 Left undetected, hearing
impairment in infants can negatively affect speech and language acquisition, academic achievement, and social and
emotional development. These negative effects can be diminished and even eliminated through early intervention at
or before 6 months of age.3 Reliable screening tests that minimize referral rates and maximize sensitivity and
specificity are available. The goal of universal neonatal hearing screening (UNHS) is to maximize linguistic and
communicative competence and literacy development for children who are hard of hearing or deaf.
In Flanders, a community-based screening program was successfully implemented by the federal health care
agency in 1998. The hearing screening program is performed with automated auditory brainstem response (AABR)
testing and aims to identify all children with a permanent unilateral or bilateral hearing impairment of ⱖ35 dB nHL.
The AABR testing is performed at the age of ⬃4 weeks. If the infant fails the initial test, then it is repeated within
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25
TABLE 3 Results From Diagnostic Audiologic Workup Versus
unilateral
Screening Results Obtained Through AABR Screening
bilateral
AABR Finding ABR Result, n (%)
Ototoxic medication
2.8%
Artificial breathing > 5
Deafness syndromes days
3.9% 4.5%
have a hearing loss, whereas 28.6% of the children with cases. Dropout of 29 (25.0%) of 116 children was ob-
risk factors had normal hearing. The distribution of the served, in which case the complete diagnostic protocol
different risk factors is presented in Fig 2. could not be conducted. A specific etiologic diagnosis
Familial history of deafness was the most frequently was established for 48 (55.2%) of the 87 children for
encountered risk factor for congenital hearing loss in our whom a permanent hearing loss was confirmed. For the
population. Risk factors were not statistically different remaining 39 children (44.8%), the cause underlying
between the normal hearing and hearing loss groups the congenital hearing loss remained unknown. The
(Kruskal-Wallis test, P ⫽ .44). distribution of the etiologic diagnoses is presented in Fig
The screening population of NICU infants demon- 3. Of the causes identified, a genetic cause was present in
strated a permanent hearing loss in 61.5% of cases. The 60.4% of cases, peripartal problems in 20.8%, and con-
male/female ratio was 3.0. The median hearing loss of genital CMV infection in 18.8%. With respect to the
the hearing-impaired children was 60 dB nHL. The genetic causes of hearing loss in our population, muta-
most-prevalent risk factors were mechanical ventilation, tions in the GJB2 gene accounted for 37.9% of the cases,
low birth weight, and hyperbilirubinemia. chromosomal aberrations were found in 13.8% (n ⫽ 4),
specific syndromic deafness for which the underlying
Etiologic Evaluation molecular basis was known was proven in 6.9% (n ⫽ 2),
Additional diagnostic testing for the permanently hear- and a yet unknown genetic factor was involved in
ing-impaired infants (n ⫽ 116) could be performed in 87 41.4% (n ⫽ 12). The last category was based on pedigree
Syndromic deafness
2.3%
CMV
FIGURE 3 No diagnosis 10.3%
Etiologic diagnoses for children with congenital permanent 44.8%
hearing loss.
CX 26
12.6%
Chromosomal
aberrations
Familial hearing loss 4.6%
13.8%
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TABLE 5 Genotype-Phenotype Correlation in Children With GJB2 ABO incompatibility (n ⫽ 2), bacterial meningitis (n ⫽
Mutations 1), and fetal alcohol syndrome (n ⫽ 1). The other labo-
ratory tests demonstrated various findings in a number
Patient GJB2 Mutation Hearing Threshold, dB nHL
of cases, without any contribution to the final etiologic
Right Ear Left Ear diagnosis. Ophthalmologic examination revealed 5 in-
1 35delG homozygote ⬎100 ⬎100 fants with eye abnormalities, including astigmatism (n ⫽
2 35delG homozygote ⬎100 ⬎100 2), eye ptosis, pseudofakia, and strabismus. In the
3 35delG/1VS1 ⫹ 1G⬎A 70 90 present population, ophthalmologic evaluations were of
4 35delG/1VS1 ⫹ 1G⬎A 50 65 only limited importance for the diagnosis of deafness.
5 35delG homozygote ⬎100 ⬎100
Radiologic imaging was performed for 37 patients
6 35delG homozygote ⬎100 20
7 35delG homozygote 60 80
(38.5%) exhibiting sensorineural hearing loss of ⱖ60 dB
8 35delG homozygote ⬎100 90 nHL (n ⫽ 96). Of those patients, 11 (29.7%) showed
9 71G⬎A homozygote ⬎120 ⬎120 positive radiologic findings. Computed tomography had
10 C101T⬎C ⫹ C71G⬎A 50 70 a slightly higher rate of abnormality detection (n ⫽ 33;
11 35delG ⫹ 35dupG 120 120 27%) than did MRI (n ⫽ 23; 21%).
In aural atresia, the classical malformations of the
external and middle ear were found. Minor inner ear
malformations at the semicircular canals were described
characteristics demonstrating a mendelian type of inher-
in 3 cases, but no Mondini-like defects were observed.
itance or specific phenotypes for which the gene or the
Electrocardiographic findings were abnormal in only 1
sequence is not yet known.
patient, with Jervell and Lange-Nielsen syndrome.
For 11 children, hearing loss was attributed to muta-
tions in the GJB2 gene. A detailed description of the
DISCUSSION
different GBJ2 mutations and the resulting hearing loss is
Hearing loss is one of the most common congenital
shown in Table 5. All of these children were either
anomalies, occurring in ⬃1 to 2 infants per 1000. Left
homozygous or compound heterozygous. Homozygotic
undetected, hearing impairment in infants can nega-
carriage of the 35delG mutation was the most common
tively affect speech and language acquisition, academic
pattern but demonstrated variable clinical expression.
achievement, and social and emotional development.
Apart from GBJ2 mutations, the following specific
These negative effects can be diminished and even elim-
genetic phenotypes were found: trisomy 21 (n ⫽ 2),
inated through early intervention at or before 6 months
partial trisomy 19p (n ⫽ 1), trisomy 18 (n ⫽ 1), Jervell
of age.3 To the best of our knowledge, this is the first
and Lange-Nielsen syndrome (n ⫽ 1), Waardenburg
report in the literature that provides data on audiologic
syndrome (WS) (n ⫽ 1), and craniofacial malformations
confirmation and etiologic assessment in a large sample
(n ⫽ 6). The last category included 4 cases of aural
of newborns referred after failed UNHS.
atresia.
Many UNHS programs are experiencing difficulty get-
For 9 children, a diagnosis of congenital CMV infec-
ting all or most of the infants referred from the screening
tion was made. CMV was detected through PCR assays
program to complete the diagnostic process and to be
with the blood spots on Guthrie cards, viral cultures, or
enrolled in intervention programs. Attrition rates as high
blood serologic tests. A detailed description of these chil-
as 60% between the initial referral and diagnostic con-
dren and their hearing thresholds at birth and at fol-
firmation are not unusual.10 Moreover, an important
low-up evaluations is presented in Table 6.
deficiency of virtually all UNHS programs is that they
Perinatal causes of hearing loss were cerebral bleeding
lack information on diagnostic evaluations.6 The current
(n ⫽ 3), asphyxia (n ⫽ 3), kernicterus attributable to
tracking system organized by the federal health care
agency seems to be very effective, because virtually all
patients sent by the organization were actually seen for
TABLE 6 Hearing Thresholds at Time of Diagnosis and Evolution in follow-up audiologic confirmation. In addition, organiz-
Children With Hearing Loss Attributable to Congenital ing the etiologic evaluation was quite efficient, with a
CMV Infection dropout rate of only 25.0%. The search for an underly-
Patient Hearing Threshold, Age at Last Follow-up Evolution ing cause must be undertaken through a multidisci-
dB nHL Evaluation, y plinary approach involving an ear, nose, and throat sur-
Right Ear Left Ear geon, a pediatrician, a geneticist, an ophthalmologist, a
radiologist, and other specialists when indicated by the
1 40 80 3.0 Stable
2 ⬎100 40 2.5 Stable
clinical findings. An efficiently managed diagnostic pro-
3 55 45 Lost to follow-up ? tocol decreases the burden for the parents and child and
monitoring limits the risk of noncompliance.
4 ⬎100 ⬎100 1.2 Stable The presence of hearing loss (either unilateral or bi-
5 70 60 2.4 Progressive lateral) was confirmed in 68.2% of the referrals. In
6 120 120 1.8 Stable 31.8%, hearing was found to be normal after a thorough
7 50 70 0.9 Stable audiometric evaluation. In 60.4% of the cases, exactly
8 40 120 1.1 Progressive analogous results were found in screening and diagnos-
9 60 100 0.8 Stable tic testing. Our results suggest that the accuracy of new-
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ulation, trisomies 18, 21, and 19p accounted for 8.3% dyssynchrony.31 In this particular case, the disorder is
(n ⫽ 4) of the identified causes of prelingual hearing loss. attributed to functional alterations in the inner hair cells.
In the literature, the most important environmental In 1 child, auditory dyssynchrony was caused by hy-
factors responsible for prelingual hearing loss are con- perbilirubinemia attributable to Rh factor incompatibil-
genital infections (mainly rubella in nonvaccinated areas ity. The child was treated with exchange transfusion
and CMV), ototoxicity, prematurity, and asphyxiation.12 during the newborn period, and later she received a
In our study group, 39.6% of the cases of permanent cochlear implant. For the other child, no risk factors
hearing loss were attributable to environmental causes. were present and mutations in the OTOF gene were
Congenital CMV infection was recognized as the most excluded.
frequent cause of acquired hearing loss in neonates. In It is obvious that identification of the cause of the
our population, congenital CMV infection was present hearing loss provides new information relevant to hear-
in 18.8% of cases. A diagnosis of congenital CMV infec- ing loss management, coexisting medical problems, and
tion was based on PCR assays with dried blood spots on the prognosis for the child and family. In addition, these
Guthrie cards, viral cultures from urine or saliva sam- investigations clarify the epidemiological features of con-
ples, and the presence of specific IgM antibodies. Con- genital deafness, which may facilitate the planning of
genital CMV infection is a challenging diagnosis.21 Once effective hearing loss prevention and surveillance pro-
children are older than 2 to 3 weeks, the diagnosis grams.
becomes sometimes difficult, because viral excretion in
the urine might be intermittent and a postnatal infection CONCLUSIONS
cannot be ruled out. In more-recent years, implementa- A diagnosis of congenital hearing loss (either unilateral
tion of PCR analysis of viral DNA in dried blood spots has or bilateral) was made for 68.2% of neonates referred for
significantly improved the diagnostic power for congen- audiometric evaluation after failed UNHS. For 55.2% of
ital CMV infection.22,23 An early diagnosis of congenital those children, an etiologic diagnosis could be made after
CMV has important implications from a therapeutic a comprehensive etiologic evaluation. This evaluation
point of view. Clinical studies with treatment protocols allows for appropriate, individually tailored rehabilita-
based on ganciclovir are underway and promising, al- tion, audiometric follow-up monitoring, and parental
though not applied in the present study.24,25 Hearing loss counseling. Our diagnostic abilities are likely to improve
attributable to congenital CMV may be progressive in in the near future, with advances in molecular genetics
⬎50% of cases,26 and regular audiometric follow-up and the rapidly expanding knowledge concerning genes
monitoring is required until the age of 6 years. Both involved in nonsyndromic sensorineural hearing loss.
aspects underscore the need for correct early diagnosis This would significantly improve the strength of UNHS
and appropriate counseling of the parents. programs and allow for the rapid identification of pre-
According to Fortnum and Davis,27 bacterial menin- lingual hearing loss.
gitis accounts for 6% of sensorineural hearing loss in
children. In a study by Koomen et al, 75% of patients ACKNOWLEDGMENT
were ⬍2 years of age.28 Bacterial meningitis was a cause We thank the audiologists in our department for their
of acquired neonatal hearing loss in 1 child (2.1%) in outstanding professional help and diligence in screening
our population. newborns.
A diagnosis of auditory dyssynchrony was estab-
lished for 2 children (4.2%). This disorder is charac- REFERENCES
terized by a dysfunction in neural/brainstem transmis- 1. Parving A, Hauch AM, Christensen B. Hearing loss in children:
sion of auditory stimuli in the presence of normal epidemiology, age at identification and causes through 30 years
outer hair cell function. This condition translates into [in Danish]. Ugeskr Laeger. 2003;165(6):574 –579
absent or abnormal ABR responses and normal oto- 2. van Straaten HL, Tibosch CH, Dorrepaal C, Dekker FW, Kok
acoustic emissions. The clinical significance is that this JH. Efficacy of automated auditory brainstem response hearing
may result in impaired development of normal audi- screening in very preterm newborns. J Pediatr. 2001;138(5):
674 – 678
tory behavior or oral language, often leading to co-
3. Yoshinaga-Itano C, Coulter D, Thomson V. Developmental
chlear implantation. According to Foerst et al,29 a outcomes of children with hearing loss born in Colorado hos-
prevalence of 0.94% was found within the group at pitals with and without universal newborn hearing screening
risk for hearing loss, compared with 8.44% among programs. Semin Neonatol. 2001;6(6):521–529
profoundly hearing-impaired children. Protocols that 4. Van Kerschaver E, Stappaerts L. ALGO Gehoorsscreening: Rapport
use otoacoustic emission screening should refer in- van de Werkjaren 2001 & 2002 [ALGO Hearing Screening: Report of
fants with hyperbilirubinemia for ABR testing, be- the Work Years 2001 and 2002; in Dutch]. San Carlos, CA: ALGO
cause there is mounting evidence in the literature Natus Medical Inc; 2003
5. Thompson DC, McPhillips H, Davis RL, Lieu TL, Homer CJ,
showing linkage between auditory dyssynchrony and
Helfand M. Universal newborn hearing screening: summary of
hyperbilirubinemia.30 In the present study, every child evidence. JAMA. 2001;286(16):2000 –2010
who needed at least phototherapy was considered at 6. Declau F, Doyen A, Robillard T, Janssens de Varebeke S. Uni-
risk for hearing loss. versal newborn hearing screening. B-ENT. 2005;1(suppl 1):
Mutations in the gene encoding otoferlin (OTOF), 16 –23
known as DFNB9, also may cause a pattern of auditory 7. Joint Committee on Infant Hearing, American Academy of
1126 DECLAU et al
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Etiologic and Audiologic Evaluations After Universal Neonatal Hearing Screening:
Analysis of 170 Referred Neonates
Frank Declau, An Boudewyns, Jenneke Van den Ende, Anouk Peeters and Paul van den
Heyning
Pediatrics 2008;121;1119
DOI: 10.1542/peds.2007-1479
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