Table 1.
Background of CMV and effects of CMV on hearing, speech and language development, and clinical outcomes in children.
| References | Study design | Population | Major findings | Search strategy | |
|---|---|---|---|---|---|
| Background (n = 9) | Foulon et al. (5) | Observational Study | 28 children born with cCMV whose mothers had a primary CMV diagnosis | Trimester in which the mother's primary CMV infection occurred was estimated and all children were screened for SNHL. Results showed that SNHL is more common in cCMV-positive infants born to mothers who became infected with CMV in their first trimester than mothers infected later in pregnancy. | 1 |
| Foulon et al. (2) | Observational Study (Prospective Longitudinal Study) | 157 children with cCMV, identified within 5 days of birth | Children with cCMV may have certain risk factors (infection before the 14th week of pregnancy, infection at birth, and imaging abnormalities) for SNHL. | 1 | |
| Fowler and Boppana (6) | Systematic Review | Mothers with CMV, babies with cCMV | There is little awareness among pregnant women and healthcare providers about cCMV and associated risks. Prenatal testing for CMV generally only occurs as part of the diagnostic evaluation for mononucleosis and similar illnesses. CMV screening technologies for newborns have improved and CMV-related SNHL is more likely to be detected thanks to routine newborn hearing screenings. Newborn CMV screenings themselves are not routine, however. Longer-term antiviral treatments for infants with symptomatic cCMV are beneficial. | 1 | |
| Fowler et al. (7) | Proposal | 99,945 newborns screened for cCMV at 7 different medical centers between 2007 and 2012 | Infants were screened for cCMV, along with their routine newborn hearing screening, while in the nursery. 7% of CMV-positive newborns failed their newborn hearing screenings, compared to only 0.9% of newborns who were not cCMV positive. Most cCMV-positive newborns who failed their hearing screening had SNHL. A targeted approach to test all newborns who fail their hearing screenings for cCMV is proposed. It is important to note that 43% of infants with CMV-related SNHL were not identified by the newborn hearing screening. | 1 | |
| Giannattasio et al. (8) | Cohort Study | 158 congenitally infected children; 93 born to mothers with primary CMV infection and 65 with non-primary infected mothers | The frequency of hearing loss and neurodevelopmental deficits in newborns does not vary with type of maternal CMV infection. | 1 | |
| Kimberlin et al. (9) | Randomized Control Trial | 2 randomly assigned groups of neonates with CMV disease involving the central nervous system | One group received 6 weeks of ganciclovir while the other group received no treatment. 21/25 in the ganciclovir group had improved or maintained hearing between baseline and 6 months old. 7/17 control patients had worsening of hearing between baseline and 6 months. Ganciclovir administered in the neonatal period may prevent hearing deterioration. | 1 | |
| Nicloux et al. (10) | Review | Newborns with cCMV | cCMV is the most common non-hereditary cause of hearing loss in children. 90% are asymptomatic at birth, and of those 90%, 5–15% are considered at-risk of experiencing neurosensory sequelae, including hearing loss. The 10% of infants who exhibit cCMV symptoms have a much higher risk of neurosensory impairment (17–60%). Even if neurosensory sequelae are not immediately present upon a cCMV diagnosis, they can be delayed, so follow-ups well beyond the neonatal period are recommended. | 1 | |
| Shearer et al. (11) | Proposal | Newborns with cCMV | cCMV testing is currently not part of the routine hearing screening a newborn undergoes, despite being one of the major causes for hearing loss in children. This proposal suggests that (limited) genetic testing and cCMV testing are implemented into the universal newborn hearing screening procedures to better identify newborns with hearing loss who may be missed by current testing protocols. | 1 | |
| Yamamoto et al. (12) | Secondary Infection Study | 11,900 newborns born to mothers in a very seropositive population, of which 68 were cCMV-positive and 91 failed their newborn hearing screening | 7/24 (29.2%) of the newborns who failed their hearing screening had cCMV. Integrating targeted cCMV screening among newborns who fail their hearing screening could be a cost-effective strategy to identifying newborns with early-onset, cCMV-related HL. | 1 | |
| Hearing loss (n = 11) | Dar et al. (13) | Cohort Study | 1,720 newborns in rural northern India who are CMV-positive and/or failed their newborn hearing screening | cCMV is the leading factor that causes permanent congenital/early-onset hearing loss. Even with nearly universal seroimmunity, there is still a strong correlation between cCMV and hearing loss. This holds true in both the developing world and more rural places, like regions of northern India, and simultaneous cCMV and hearing screenings are both possible and beneficial in a resource-limited setting. | 1 |
| Demmler-Harrison et al. (14) | Longitudinal Study | 237 infant-mother pairs with maternal CMV, followed child from birth-18 years of age | Primary and non-primary CMV during pregnancy may result in symptomatic or asymptomatic cCMV. SNHL occurred most commonly after maternal primary infection with CMV. This HL was detected within the first year of life in most cases. | 1 | |
| Fletcher et al. (15) | Systematic Review | Children with cCMV-induced SNHL, from 36 articles regarding the history and rehabilitative outcome of cCMV-induced SNHL | 9–68% of cCMV-induced SNHL is delayed, meaning it is not uncommon for newborns with cCMV to pass their newborn hearing screenings undetected. In 7–71% of cases, SNHL was progressive. Frequent audiologic evaluation of children who are cCMV-positive is necessary considering the natural history of cCMV-related hearing loss. Because so many cCMV-positive newborns are asymptomatic, universal neonatal screening should be considered. | 1 | |
| Kim et al. (16) | Retrospective Case Study | 58 children born with cCMV | 11/58 (19%) of children with confirmed cCMV infections at birth also had SNHL. Most confirmed HL cases passed their newborn hearing screening and were diagnosed only after re-evaluation following a CMV test. It is important to still perform timely audiologic evaluations of children who are identified to have cCMV, even if they initially passed their newborn hearing screening. | 1 | |
| Korver et al. (3) | Systematic Review | children with congenital hearing loss identified at birth due to genetics or infection | Several genetic disorders and infections may result in hearing loss in children. It is important for professionals to focus on early diagnosis and treatment of hearing loss for optimal results. | 1 | |
| Lanzieri et al. (17) | Longitudinal Study | 92 case patients and 51 controls; assessment was completed with auditory brainstem response and behavioral audiometry | Delayed-onset and progression of SNHL continued through adolescence for children with asymptomatic congenital cytomegalovirus. The risk of developing SNHL after 5 was not different than in uninfected children. | 1 | |
| Lanzieri et al. (18) | Longitudinal Prospective Cohort Study | 96 case patients of which 4 were symptomatic and 92 asymptomatic. | Congenital/early-onset SNHL frequently resulted in severe to profound HL in both asymptomatic and symptomatic cases. | 1 | |
| Riga et al. (19) | Systematic Review | 181 children with cCMV-induced hearing loss | The prevalence of cCMV-induced hearing loss was significantly higher among children who were symptomatic and were also much more likely to develop bilateral hearing loss. Infants with cCMV should be closely monitored during their preschool years, regardless of hearing status, since hearing thresholds can change substantially long after the neonatal period. | 1 | |
| Rosenthal et al. (20) | Longitudinal Follow-up Study | 580 children with cCMV | Urine/saliva samples from 580 children were collected and analyzed for CMV “shedding.” Prevalence of culture positivity decreased significantly after 3 years of age. Delayed HL is strongly associated with symptomatic infection at birth, but many asymptomatic children also developed HL. Longer duration of CMV shedding could predict delayed HL. | 1 | |
| Salomè et al. (21) | Prospective Study | 102 children with asymptomatic CMV | The long-term audiologic outcomes of 102 children with asymptomatic CMV were measured from 2002 to 2018. Following a mean follow-up period of 3.3 years, none of these 102 children developed SNHL. Only 14 presented with a a variable hearing impairment. Overall, these data suggest that there is a relatively low risk of delayed hearing loss if a cCMV-infected child is asymptomatic during the first month of life. | 1 | |
| Verbeeck et al. (22) | Comparative Study | 194 infants with indicative hearing impairment, 332 matched controls in Flanders, Belgium | Significantly more infants with hearing impairments were cCMV positive. The presence of CMV before or shortly after birth influences the outcome of hearing impairment. Follow-up study suggests that the hearing impairment of children infected with CMV after birth are less likely to improve than children who are CMV-negative. | 1 | |
| Speech/ Language (n = 3) | De Kegel et al. (23) | Longitudinal Study | 64 children with cCMV assessed at 6, 12, and 24 months old | cCMV is a risk factor for early motor development delays. | 1 |
| Lopez et al. (24) | Comparative Study | Children born with cCMV (some of whom have SNHL), and matched controls | cCMV-positive children with SNHL scored significantly lower on full-scale intelligence and receptive vocabulary tests than their normal hearing peers. There were no significant differences among the groups for verbal-nonverbal intelligence, expressive vocabulary, and reading/math achievements. | 1 | |
| Zhang et al. (25) | Cohort Study | 49 children age birth-6 years in Qinba, China | Asymptomatic cCMV did not relate to physical or intellectual disability, but it may be a predictor of poorer long-term development of language. | 1 | |
| Clinical outcomes (n = 5) | Cannie et al. (26) | Cohort Study | 51 fetuses with cCMV; 121 total confirmed patients with cCMV | cCMV can be identified with MRI as early as 27 to 33 weeks gestation. 18 infants showed post-natal SNHL, 10 infants showed post-natal neurological impairment. | 2 |
| Corazzi et al. (27) | Retrospective Case Control Study | Children with both symptomatic and asymptomatic cCMV who received CIs, children the Connexin 26 mutation who received CIs | Connexin 26 mutations are known to cause hereditary bilateral SNHL, and cCMV is known to be the leading cause of non-hereditary SNHL. Children with symptomatic cCMV who received CIs and speech therapy struggled to obtain language more than their asymptomatic cCMV peers and those with Connexin 26 mutations. Regardless, CI usage supported by speech therapy is an excellent intervention plan for cCMV-positive children who suffer from SNHL. | 1 | |
| Diogo et al. (28) | Systematic Review | fetuses with cCMV; MRI findings at 29, 31, 34, and 36 gestational weeks | Imaging reveals abnormal brain structures in developing fetuses exposed to CMV, one of the more common abnormalities being lesions in the temporal lobe. Parental and healthcare professional education is recommended, in addition to future research and a solidified screening protocol for prenatal identification of cCMV. | 2 | |
| Laccourreye et al. (29) | Cohort Study | 15 children with profound HL from cCMV; assessed 3 months pre- and post- cochlear implantation | Children with typical anatomy (as shown on MRI) demonstrated improved hearing and speech production following cochlear implantation. For those with abnormal MRI results, speech therapy and balance rehabilitation were recommended for best outcomes. | 1 | |
| Natale et al. (30) | Retrospective Case Study | 60 infants born with asymptomatic cCMV, none of whom underwent antiviral treatment | 16/60 (26.67%) of infants had some form of auditory neuropathy, mainly moderate. However, all 16 of these infants spontaneously recovered a normal auditory threshold over time. A delayed maturation of the auditory system should be considered when an isolated mild-moderate SNHL is found at birth as a result of cCMV. | 1 |
cCMV, congenital cytomegalovirus; CMV, cytomegalovirus; HL, hearing loss; MRI, magnetic resonance imaging; SNHL, sensorineural hearing loss.