Managing challenges in congenital CMV: current thinking.

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants.

Vestibular and balance dysfunction in children with congenital CMV: a systematic review.

OBJECTIVE: This systematic review evaluates vestibular and balance dysfunction in children with congenital cytomegalovirus (cCMV), makes recommendations for clinical practice and informs future research priorities. DESIGN: MEDLINE, Embase, EMCARE, BMJ Best Practice, Cochrane Library, DynaMed Plus and UpToDate were searched from inception to 20 March 2021 and graded according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. PATIENTS: Children with cCMV diagnosed within 3 weeks of life from either blood, saliva and/or urine (using either PCR or culture). INTERVENTION: Studies of vestibular function and/or balance assessments. MAIN OUTCOME MEASURES: Vestibular function and balance. RESULTS: 1371 studies were identified, and subsequently 16 observational studies were eligible for analysis, leading to an overall cohort of 600 children with cCMV. All studies were of low/moderate quality. In 12/16 studies, vestibular function tests were performed. 10/12 reported vestibular dysfunction in ≥40% of children with cCMV. Three studies compared outcomes for children with symptomatic or asymptomatic cCMV at birth; vestibular dysfunction was more frequently reported in children with symptomatic (22%-60%), than asymptomatic cCMV (0%-12.5%). Two studies found that vestibular function deteriorated over time: one in children (mean age 7.2 months) over 10 months and the other (mean age 34.7 months) over 26 months. CONCLUSIONS: Vestibular dysfunction is found in children with symptomatic and asymptomatic cCMV and in those with and without hearing loss. Audiovestibular assessments should be performed as part of neurodevelopmental follow-up in children with cCMV. Case-controlled longitudinal studies are required to more precisely characterise vestibular dysfunction and help determine the efficacy of early supportive interventions. PROSPERO REGISTRATION: CRD42019131656.

Hearing-impaired young people - a physician's guide .

Physicians reading this will have a broad range of in-depth knowledge about their own subspecialty. However, in daily medical practice there are topics of which all physicians should have some knowledge. Those who deal with young people should have some knowledge of the needs of the hearing-impaired population within this group of patients. This article is intended to provide an overview of young people with hearing impairment (HIYP), the challenges they face and what we can do to help them. In this paper, we assume that data published regarding hearing-impaired children apply to HIYP from 13 years (the age at which the transition process begins) to 25 years of age (the age at which 'youth' according to the World health Organization and the Education Health Care Plan ends).

Evaluating the feasibility of integrating salivary testing for congenital CMV into the Newborn Hearing Screening Programme in the UK.

UNLABELLED: Congenital cytomegalovirus (cCMV) accounts for 20% of all childhood sensorineural hearing loss (SNHL) but is not routinely tested for at birth. Valganciclovir has been shown to prevent hearing deterioration and improve neurocognitive outcomes if started in the first month of life. This study aimed to assess the feasibility of integrating testing for cCMV using salivary swabs into the Newborn Hearing Screening Programme (NHSP). Parents of newborns <22 days old in South West London, who were referred after their initial newborn hearing screen for further audiological testing, were approached by hearing screeners to obtain a saliva sample for CMV DNA polymerase chain reaction (PCR). Eighty percent (203/255) of newborns who were eligible had a saliva swab taken by the hearing screener. Over 99% of results were delivered within the first month of life. Two newborns were identified with cCMV and both seen on day 10 of life by the paediatric specialist. All saliva samples tested delivered a result using real-time PCR. CONCLUSION: It is feasible for hearing screeners to obtain saliva swabs to test for CMV DNA using real-time PCR in newborns referred after their initial hearing screen. Rapid diagnostic testing for cCMV needs a more detailed clinical and cost-effectiveness analysis.

Feasibility and acceptability of targeted screening for congenital CMV-related hearing loss.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. Ganciclovir has been shown to prevent the continued deterioration in hearing of children with symptomatic cCMV, but some children with cCMV-related SNHL are unidentified in the neonatal treatment period. Neonatal cCMV screening provides an opportunity to identify infants with cCMV-related SNHL who might benefit from early treatment. OBJECTIVES: To assess the feasibility (ability to take samples before 3 weeks of age and clinical assessment by 30 days of age) and acceptability (maternal anxiety) of targeted CMV testing of infants who are 'referred' for further audiological testing after routine newborn hearing screening programme (NHSP). METHODS: Parents of infants who have 'no clear responses' on routine NHSP before 22 days of life in London and North East England were approached. Salivary and urine samples were tested by CMV PCR. At recruitment and 3 months, the short form Spielberger State-Trait Anxiety Inventory measured maternal anxiety. RESULTS: 411 infants were recruited. 99% (407/411) returned a sample; 98% (404/411) successfully yielded a CMV result, 6 had cCMV, all diagnosed on salivary samples taken <22 days of age (1.5%; 95% CI 0.6% to 3.2%). Only 50% returned urine samples compared with 99% returning salivary samples (p<0.001). Using saliva swabs 98% were successfully screened for CMV within 3 weeks. All positive screening CMV results were known by day 23, and 5/6 infants with cCMV were assessed within 31 days. Anxiety was not increased in mothers of infants screened for cCMV. CONCLUSIONS: Targeted salivary screening for cCMV within the NHSP is feasible, acceptable and detects infants with cCMV-related SNHL who could benefit from early treatment.

Use of stored dried blood spots for retrospective diagnosis of congenital CMV.

The diagnosis of congenital cytomegalovirus infection cannot be made with certainty in children presenting after the perinatal period, unless stored early samples are available for diagnostic testing. This has led to uncertainty in confirming the overall contribution of CMV to hearing loss and neurodevelopmental impairment. The use of dried blood spots (DBSs) to retrospectively diagnose infection in children with compatible symptoms may be helpful diagnostically although there are ongoing uncertainties regarding the stability of viral DNA in cards, the risk of contamination between cards, and sensitivity and specificity in a clinical setting. This report aims to address these areas and evaluate the use of DBS testing in our hands in the United Kingdom to date. Results from testing artificially prepared cards and cards from three populations of children suggest a high specificity for congenital CMV infection and a good sensitivity for cases where sensorineural hearing loss is caused by congenital CMV.

Cytomegalovirus.

PURPOSE OF REVIEW: To identify recent developments in the management of congenital cytomegalovirus infection which continues to exact a heavy toll on the developing central nervous system. RECENT FINDINGS: A major advance is the publication of a randomized controlled trial showing that hearing loss is significantly decreased by ganciclovir. This treatment should now be offered to all neonates who would have met the eligibility criteria of the trial, that is proven congenital infection with central nervous system involvement when treatment is begun within 1 month of birth. A second major advance is the use of stored dried blood spots to detect cytomegalovirus DNA and so differentiate congenital infection from perinatal infection. This approach has the potential to diagnose a proportion of cases of hearing loss and mental retardation which are currently labelled idiopathic. A third major advance is the clinical evaluation of vaccines against cytomegalovirus. Experiments with guinea pig cytomegalovirus show reduced fetal mortality and congenital infection among dams given vaccines containing the glycoprotein B of the virus. A different vaccine glycoprotein B construct has been shown to be immunogenic and well tolerated in healthy adult and paediatric humans. Recent reviews from the Institute of Medicine and the National Vaccine Advisory Committee emphasize the financial and humanitarian justifications for developing cytomegalovirus vaccines as a high priority. SUMMARY: Substantial progress has recently been made in diagnosis and treatment. If additional financial support were to be made available to evaluate existing vaccine candidates in controlled clinical trials, congenital cytomegalovirus could potentially become a vaccine-preventable disease.