Hearing status in children with congenital cytomegalovirus: Up-to-6-years audiological follow-up
Introduction
Congenital cytomegalovirus (cCMV) is a major cause of congenital infection. Its birth prevalence is estimated at 0.64–2% [1], [2], [3]. cCMV causes central nervous system and sensory impairments with hearing impairment being one of the most common sequelae. Of all infected newborns, only 5–10% have clinically apparent symptoms at birth [2], [4]. However, sensorineural hearing loss (SNHL) can occur in both asymptomatic and symptomatic children, at birth or later in childhood. The hearing loss can be unilateral or bilateral and varies from mild to profound. Over time, progression or fluctuation of the hearing loss can occur [1], [2], [4], [5]. Therefore, long-term audiological follow-up is crucial in this population. In Belgium, pregnant women are not generally screened for CMV. Only women who are at risk for infection, such as teachers and nannies, are tested routinely during pregnancy. In accordance to the Flemish CMV protocol started in 2003, all children with a CMV seroconversion during pregnancy and confirmed CMV infection at birth, receive systematic audiological follow-up until 6 years of age.
The protocol for treatment of newborns with cCMV at the Neonatal Intensive Care Unit (NICU) of the University Hospital of Leuven, Belgium, proposes a treatment with ganciclovir to all newborns with hearing loss in combination with other CMV-induced lesions. The treatment may reduce hearing deterioration and increase improvement of the hearing thresholds [6], [7]. Improvement of other neurological symptoms has also been documented [8]. Treatment includes a 6 week intravenous administration of the drug. Not all parents consent to the treatment because of the severe side effects and the long stay at the hospital.
Over the past years, ganciclovir, a nucleoside analogue, has been used to treat congenital CMV infection. In vivo, ganciclovir is converted into ganciclovir triphosphate, which inhibits CMV DNA polymerases by competitively inhibiting the incorporation of deoxyguanosine triphosphate into elongating viral DNA. After the release of pyrophosphate, ganciclovir monophosphate is incorporated into the end of a growing chain of viral DNA, thereby slowing down replication. The drug can be monophosphorylated to a certain extent by normal, uninfected or non-transfected cells, possibly explaining its cytotoxic side effects (myelosuppression) in human patients [7]. Potential side effects include hematological abnormalities, especially neutropenia, and catheter-related problems, such as infection and catheter malfunction. Hematological abnormalities are transient, but may necessitate dose adjustment or therapy interruption.
The importance of early detection of hearing loss and early intervention to improve language development and later on educational outcomes is well known [9]. In Flanders, a region of Belgium, Kind & Gezin (“Child & Family”), a Flemish public child care organization, runs a hearing screening program since 1998. Hearing screening is conducted using an automated auditory brainstem response (AABR) test, the ALGO (Natus Medical Inc., ALGO® and ALGO®3i). The neural response to a 35 dBnHL click stimulus is scored as pass or fail, based on template-matching algorithms. The child is referred after two failures at the ALGO-test. In the 1999–2004 period, a screening offer was made to 97.91% of all newborns in Flanders [10]. Since 2003, the Ear–Nose–Throat department of the University Hospital of Leuven offers hearing screening, using AABR at 35 dBnHL, at the Neonatal Intensive Care Unit to newborns, who are at risk of hearing loss. Test results are passed on to Kind & Gezin. The aim is to detect hearing loss as soon as possible in high-risk newborns. This prospective study will describe the audiological outcomes of 97 children with cCMV, tested at the ENT department of the University Hospital Leuven.
Section snippets
Subjects
The study population consisted of 97 children, 61 boys and 36 girls, born between January 2003 and July 2009. Children were entered upon a cCMV confirmation during pregnancy.
Audiological assessment
In 2003, a number of hospitals in Belgium, including the University Hospital of Leuven, set up a protocol for the audiological follow-up of children with CMV seroconversion during pregnancy. This protocol is referred to as the “Flemish CMV protocol”. Following the protocol, every newborn undergoes a hearing screening within
Results
During the study period, 97 children entered the protocol at the University Hospital of Leuven. The mean follow-up time until December 2009 is 2.4 years ± 1.5 years, the first child now being in follow-up for six years. Under the protocol, every child should be monitored until the age of six. For 23 children, follow-up stopped early for various reasons. Some of them went to another medical centre, others stopped follow-up early despite detailed information. Table 1 gives an overview of the number
Discussion
The exact prevalence of cCMV and its impact on the etiology of SNHL in Belgium is not yet known, because there is no systematic screening for CMV during pregnancy or at birth. One prospective study has been performed at a maternity ward in Brussels covering 14,021 births with a prevalence of 0.53% [1]. Many cCMV-infected children are born with normal hearing and without any clinically apparent symptoms. As a consequence, even criterion-based screening for CMV will not be sufficient. Standard
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Hearing loss caused by CMV infection is correlated with reduced endocochlear potentials caused by strial damage in murine models
2022, Hearing ResearchCitation Excerpt :Sensorineural hearing loss (SNHL) is the most common permanent disability resulting from congenital CMV infection (e.g. Demmler 1991; Foulon et al. 2012; Fowler et al. 1999; Hicks et al. 1993; Manicklal et al. 2013; Misono et al. 2011; Park et al. 2014; Pass et al. 2006; Royackers et al. 2011; Stagno et al. 1986).
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2021, Early Human DevelopmentCitation Excerpt :Hearing loss can be of variable severity and is unilateral in more than half of the cases. [23,24]. Of children with clinical apparent signs at birth, up to 40% have SNHL, whereas only 5–10% of the children without any clinical signs have SNHL. [24] This is also reflected in our population.
Early Identification and Management of Congenital Cytomegalovirus
2021, Otolaryngologic Clinics of North AmericaCitation Excerpt :The Joint Committee on Infant Hearing has stated that “early and more frequent assessment” might be indicated for children with cCMV infection as compared with their recommendation of “at least one” additional audiology assessment by 24 to 30 months of age for children who pass newborn hearing screening but have risk factors for hearing loss.33 Other monitoring recommendations for delayed onset of hearing loss in children with cCMV vary from every 6 to 12 months until age 4 to 6 years (see Fig. 1).4,20,34 The risk of delayed-onset SNHL is reported to return to a level comparable to non-cCMV-infected controls by age 5 years.9
Implications of dried blood spot testing for congenital CMV on management of children with hearing loss: A preliminary report
2019, International Journal of Pediatric Otorhinolaryngology