The major challenge with linking CMV testing with newborn hearing screening is whether treatment with valganciclovir would be of value in congenital CMV infection and isolated hearing loss. Studies of children with symptomatic central nervous system congenital CMV disease provide evidence of improvement (or lack of progression) in hearing loss in those treated with valganciclovir. Few, if any of these children had isolated hearing loss in this pivotal study.6 An observational study reported improved outcomes in 55 of 59 (93%) children with congenital CMV and isolated SNHL treated with valganciclovir between birth to 12 weeks of life.7 Hearing improved in nearly 70% of ears, 27% showed no change, and only 3% demonstrated progression of hearing loss; most of the improved ears returned to normal hearing. Currently, a National Institutes of Health study (ValEAR) is recruiting CMV-infected infants with isolated SNHL and randomizing them to treatment with valganciclovir or placebo. The goal is to determine if infants treated with valganciclovir will have better hearing and language outcomes.
Linking CMV testing to those who fail newborn hearing screening programs is an important step, as it appears such children are at least five times more likely to be infected with CMV than is the overall birth cohort. However, such strategies fall short of identifying the majority of newborns with congenital CMV infection, who are completely asymptomatic yet are at risk for development of complications that potentially have substantial impact on their quality of life. Although the availability of sensitive and specific PCR testing in saliva provides a pragmatic approach to identify infected children, many questions remain. First, would a confirmatory test be necessary, such as urine PCR (now considered the gold standard by many CMV experts)? Second, once identified, what regimen for follow-up testing would be indicated to identify those with early SNHL or retinopathy, and until what age? Third, is there a role for treatment in asymptomatic infection? Would that treatment be prophylactic, prior to the development of clinical signs, or implemented once early evidence of SNHL or retinopathy is present?
Dr. Stephen I. Pelton
The Valgan Toddler study – sponsored by NIH and the University of Alabama as part of the Collaborative Antiviral Study Group – will enroll children who are aged 1 month through 3 years and who had a recent diagnosis of hearing loss (within the prior 12 weeks) and evidence of congenital CMV infection. The purpose of this study is to compare the effect on hearing and neurologic outcomes in infants aged 1 month through 4 years with recent onset SNHL who receive 6 weeks of valganciclovir versus children who do not receive this drug. The results of such studies will be critical for the development of best practices.
In summary, the licensure of a rapid PCR-based tool for diagnosis of CMV infection from saliva adds to our ability to develop screening programs to detect asymptomatic infants with congenital CMV infection. The ability to link newborns who fail hearing screening programs with CMV testing will lead to more detection of CMV-infected neonates, both with isolated hearing loss, and subsequently with no signs or symptoms of infection. There is an urgent need for evidence from randomized clinical trials to enable the development of best practices for such infants.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University and senior attending physician at Boston Medical Center. Dr. Lapidot is a senior fellow in pediatric infectious diseases, Boston Medical Center. Neither Dr. Pelton nor Dr. Lapidot have any relevant financial disclosures. Email them at pdnews@mdedge.com.
References
1. J Pediatric Infect Dis Soc. 2019 Mar 28;8(1):55-9.
2. N Engl J Med 2011 Jun 2; 364:2111-8.
3. Pediatrics. 2008 May;121(5):970-5
4. J Clin Virol. 2018 May;102:110-5.
5. J Pediatric Infect Dis Soc. 2019 Mar;8(1):55-9.