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CMV Hearing Loss

last modified on: Wed, 10/21/2020 - 21:06

Return to: Hearing Loss Clinic


CONGENITAL CYTOMEGALOVIRUS (cCMV) PREVALENCE:

  • Dependent on geography and socioeconomic factors.
  • Worldwide: 0.2 – 2.5% of all live births
  • Industrialized countries: 0.58-0.70% of all live births

TRANSMISSION:

  • Children are at greater risk of infection during primary maternal CMV infections but the majority of cCMV cases are linked to reactivation or reinfection. Children are also at greater risk during the first trimester.
  • Routine maternal screening is not currently recommended both for economic reasons and because previous infection and seroprevalence, while associated with an increased risk, is not predictive of cCMV in the newborn. Avoiding sharing food and drink with children and thorough hand washing are common recommendations to avoid infection during the prenatal period.

PRESENTATION:

  • Congenital CMV infections are generally categorized into either symptomatic or asymptomatic infections.
  • Symptomatic infections include a varied combination of intrauterine growth retardation (IUGR), microcephaly, intracranial calcifications, lack of coordination, significant cognitive delays, sleep issues, hearing loss, cerebral palsy, jaundice, hepatosplenomegaly, thrombocytopenia, pancytopenia, petechia. These children are often easily identifiable at birth with confirmatory laboratory testing. Only 10% of children who test positive for cCMV are symptomatic at birth.
  • Historically, isolated hearing loss now attributed to cCMV has not been included in the category of a “symptomatic” infection. Asymptomatic cCMV with isolated hearing loss is therefore a distinct category.

HEARING LOSS:

  • Congenital CMV is the most common non-genetic cause of congenital hearing loss. 20-25% of all congenital hearing loss.
  • The pattern of hearing loss in cCMV is extremely variable. Approximately 30% of symptomatic children have hearing loss compared to only 10% of asymptomatic children. Symptomatic hearing loss has a higher rate of bilateral as well as delayed hearing. There is no conclusive evidence of acquired CMV causing hearing loss.
  • Children will present as either unilateral to bilateral and from mild to profound. There is a high degree of observed progression and fluctuation. There is also a significant portion of children with delayed hearing loss attributed to cCMV. Meta-review has shown heterogeneity of hearing loss with CMV with some notable trends. Symptomatic CMV is more likely to be bilateral (~70%) compared to asymptomatic CMV (~40%). Both have a large proportion of severe to profound hearing loss (~77%).

MECHANISM:

  • Unknown. Mouse models show no significant inner ear histopathology but persistent inflammation in cochlea suggestive of mechanism. Natural killer cells have been implicated.
  • Evidence has not supported a hypothesis suggesting cCMV induces genetic mutation

DIAGNOSIS:

  • Symptomatic cCMV can often be part of the differential diagnosis before birth, either from known maternal CMV infection or IUGR, periventricular calcifications and microcephaly on ultrasound. While not common, amniotic fluid PCR is possible. In these situations, a poor outcome is likely.
  • Saliva rapid culture – time consuming
  • Saliva or urine PCR – cheaper, faster. Must be completed within the first 21 days. After this time, it is not possible to distinguish between congenital and acquired CMV.
    • In the case of saliva testing, false positives can result from recent breastfeeding if the mother is seropositive and care must be taken in the collection of samples. One study, using a second saliva PCR on positive patients 3 days later, found a generous false positive rate (58.6%) with saliva testing alone. Many centers advocate subsequent confirmatory urine testing.
  • Dried blood spot (DBS) PCR:
    • Collected on Guthrie cards at birth, offer an alternative test if a child is outside the initial 21 day window.
    • DBS testing has been found to have great specificity but unfortunately very low sensitivity (~35%).
    • Only available tool for retrospective diagnosis – especially in the child with delayed asymptomatic hearing loss.'
  • Screening:
    • No standard protocol in the United States
    • Universal screening has been proposed but not currently adopted at a policy level
    • Currently 5 states have legislation mandating targeted cCMV screening after a failed hearing screen (Iowa, Utah, Illinois, New York, Connecticut) (NationalCMV.org accessed 3/13/19)
      • Many other states are considering similar legislation
    • Increase in CMV screening will necessitate increased understanding of hearing loss in asymptomatic cCMV as well as treatment options.

TREATMENT:

  • Antiviral treatment
    • Valganciclovir protocol for isolated cCMV hearing loss
    • Needs to be started within the first month of life and generally continues daily
    • RCT completed for children with symptomatic cCMV (Kimberlin 2015).
    • Consensus guidelines suggest that therapy should NOT routinely be recommended for children with congenital CMV with isolated sensorineural hearing loss (SNHL) (Rawlinson 2017).
    • After this consensus statement was published a retrospective study of children with isolated SNHL who had antiviral therapy was conducted showing 69% improvement in affected ears (Pasternak 2018).
    • There are currently further trials being conducted for the efficacy of Valganciclovir in asymptomatic CMV.
  • Amplification
    • Many children do well with amplification alone
    • Frequent monitoring is often required given progressive and fluctuating nature of hearing loss in cCMV. Low threshold for repeat testing
  • CI response
    • Many patients with severe to profound hearing loss will require cochlear implantation.
    • Long term language perception and production has been good in this population, with the caveat that many have motor or cognitive delay. (Yoshida 2017)

SUGGESTED READING:

  • UpToDate. Accessed March 13, 2019.
  • Goderis, J., et al. “Hearing Loss and Congenital CMV Infection: A Systematic Review.” Pediatrics, vol. 134, no. 5, 2014, pp. 972–982., doi:10.1542/peds.2014-1173.

REFERENCES:

  • Boppana SB. Dried Blood Spot Real-time Polymerase Chain Reaction Assays to Screen Newborns for Congenital Cytomegalovirus Infection. Jama. 2010;303(14):1375. doi:10.1001/jama.2010.423.
  • Fletcher KT, Horrell EMW, Ayugi J, et al. The Natural History and Rehabilitative Outcomes of Hearing Loss in Congenital Cytomegalovirus. Otology & Neurotology. 2018;39(7):854-864. doi:10.1097/mao.0000000000001861.
  • Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Seminars in Perinatology. 2018;42(3):149-154. doi:10.1053/j.semperi.2018.02.002.
  • Kimberlin, David W., et al. “Valganciclovir for Symptomatic Congenital Cytomegalovirus Disease.” New England Journal of Medicine, vol. 372, no. 10, 2015, pp. 933–943., doi:10.1056/nejmoa1404599.
  • Pasternak, Yehonatan, et al. “Valganciclovir Is Beneficial in Children with Congenital Cytomegalovirus and Isolated Hearing Loss.” The Journal of Pediatrics, vol. 199, 2018, pp. 166–170., doi:10.1016/j.jpeds.2018.02.028.
  • Leruez-Ville M, Magny J-F, Couderc S, et al. Risk Factors for Congenital Cytomegalovirus Infection Following Primary and Nonprimary Maternal Infection. Clinical Infectious Diseases. 2017;65(3):398-404. doi:10.1093/cid/cix337.
  • Rawlinson, William D, et al. “Congenital Cytomegalovirus Infection in Pregnancy and the Neonate: Consensus Recommendations for Prevention, Diagnosis, and Therapy.” The Lancet Infectious Diseases, vol. 17, no. 6, 2017, doi:10.1016/s1473-3099(17)30143-3.
  • Yoshida H, Takahashi H, Kanda Y, Kitaoka K, Hara M. Long-term Outcomes of Cochlear Implantation in Children With Congenital Cytomegalovirus Infection. Otology & Neurotology. 2017;38(7). doi:10.1097/mao.0000000000001483.