Investigators from several Israeli institutions conducted a retrospective study of infants with isolated sensorineural hearing loss (SNHL) from congenital cytomegalovirus (cCMV) to assess the efficacy of valganciclovir on hearing status. Infants were included if they (a) had cCMV, defined as a positive urine culture or polymerase chain reaction on a specimen taken during the first 2 weeks of life; (b) were followed up for at least 1 year at the study hospital from 2005 to 2017; (c) had a pathologic hearing evaluation at birth by means of brainstem auditory evoked response (BAER); (d) did not have other central nervous system or non-central nervous system manifestations of cCMV; and (e) had started in the first 12 weeks of life either IV ganciclovir at 5 mg/kg/day for 6 weeks followed by oral valganciclovir at 17 mg/kg/dose in 2 daily doses for 6 weeks and then 1 daily dose to complete 12 months or oral valganciclovir at 17 mg/kg/dose in 2 daily doses for 12 weeks followed by 1 daily dose to complete 12 months.
The primary outcome was hearing status, defined as the change in BAER results in each affected ear from birth to the follow-up study visit. Follow-up visits occurred when study participants were ≥1 year old, and BAER results were categorized at each time as normal (<25 dB HL) or as mild (25–44 dB HL), moderate (45–69 dB HL), or severe (≥70 dB HL) hearing loss. A secondary outcome was neutropenia as a side effect of treatment, defined as an absolute neutrophil count of ≤1,000/mm3. Complete blood cell counts were obtained from infants every other week for the first 12 weeks and then every 4–6 weeks. Investigators used chi-square tests to test the association of change in hearing status by baseline BAER category.
There were 59 infants included in analysis. Isolated SNHL was unilateral in 38 (64%) and bilateral in 21 (36%), resulting in 80 affected ears. Most infants (93%) had been born at ≥37 weeks, and 52% were female.
At follow-up, hearing status improved from baseline in 55 of 80 affected ears (69%); 2 (3%) worsened. Of the affected ears that improved, most (96%) returned to normal. A higher proportion of ears with mild (vs moderate or severe) hearing loss at baseline improved (P<.001). Neutropenia occurred in 19 infants (32%), though only 1 infant required treatment change (temporary discontinuation of valganciclovir).
The investigators conclude that the hearing status of infants with isolated SNHL from cCMV improves with valganciclovir treatment.
Commentary
Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
Natural history studies have demonstrated that up to 47% of children with asymptomatic cCMV and SNHL show improvement in hearing thresholds.1 Those with milder degrees of hearing impairment are more likely to have a return to normal hearing, as was noted in the present study. Consequently, it is difficult to ascribe improvement to valganciclovir because all infants with isolated SNHL received antiviral therapy for 12 months in the current study. Two different treatment regimens were used at the discretion of the treating physician, and the investigators did not specify how many infants received each regimen. Neither of these regimens was assessed in the controlled study by Kimberlin et al,2 which limited therapy to 6 months. It is not clear whether the additional 6 months of therapy used in the current study adds benefit. The investigators assessed for neutropenia, a risk of valganciclovir therapy, but other potential side effects, including carcinogenicity and gonadotoxicity,3 could not be assessed in the current short-term study.
Utah and Connecticut have implemented targeted CMV screening of newborns who fail their newborn hearing screens.4,5 Those who are identified as having cCMV infection undergo additional evaluations, including blood cell counts, liver function tests, and brain ultrasonography, to assess for other manifestations of cCMV.6 For those with only isolated SNHL from cCMV, providers can confidently recommend follow-up hearing assessments and early interventions to minimize the effect of the hearing impairment.3 Well-designed clinical trials, currently underway, will better inform discussions about the benefits and risks of antiviral therapies for this group of infants.3
Bottom Line
Isolated SNHL may be the only manifestation of cCMV infection and may improve with valganciclovir treatment. These infants deserve close audiology follow-up. (See AAP Grand Rounds, 2018;39[2]:19.7)
EDITORS’ NOTE
The recognition that children with cCMV may have delayed onset of isolated hearing loss and may benefit from antiviral therapy has led to renewed interest in universal newborn screening for cCMV. Although CMV polymerase chain reaction on salivary samples is a sensitive screening methodology, its feasibility awaits confirmation.3
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