Our understanding of the role of congenital viral infection and hearing loss, and specifically congenital Cytomegalovirus (CMV) infection, has improved dramatically over the past few years and reports cite as many as 1% of all infants born in the US are infected with CMV 36–44
. Sensorineural hearing loss (SNHL) represents one of the most common sequelae of congenital CMV infection in infants and another large group of children with so-called “asymptomatic CMV infection” may present with hearing loss alone and no other CMV-related manifestations (e.g. no hepatosplenomegaly, petichiae, retinitis, microcephaly, brain calcifications, etc)36, 40, 45
. Making this topic even more clinically compelling are newer data now demonstrating that treatment of children with congenital symptomatic CMV infection (with intravenous ganciclovir)can stabilize or even rescue hearing if the CMV infection is diagnosed and treated early 36–38, 46
. As a result, clinicians are now presented with the challenge of quickly identifying infants with congenital CMV infection (and CMV-related hearing loss)in order to allow delivery of medical therapies that might actually stabilize or improve hearing for these infants.
One of the best windows of opportunity to screen for congenital CMV infection would be at the newborn period. Preliminary studies have already documented the feasibility of using blood spots from a Guthrie card as a DNA sample for polymerase chain reactions(PCRs) that would allow amplification of viral DNA sequences which in turn would indicate congenital CMV infection. Alternatively, simple and non-invasive sampling of infant saliva is another excellent source for culturing or sampling of virus since CMV is typically concentrated in salivary secretions 47, 48
Such a scheme obviously suggests a “hybrid” newborn hearing screening process in which physiologic hearing testing (OAE, AABR, wideband reflectance) is coupled with clinical laboratory-type screening methodologies to enhance the sensitivity and specificity of the newborn “hearing” screening. While such laboratory testing has traditionally been delegated to the diagnostic workup phase of an infant with congenital hearing loss, it is worthwhile considering the benefits of exploiting new diagnostic technologies and new knowledge of virally-mediated hearing loss and its treatment, to enhance the screening/diagnostic process and potentially reach a successful treatment phase in a shorter time frame. Taking into consideration the substantial lost-to-follow up challenges faced by most newborn hearing screening programs, it is even more compelling to consider performing as much screening, diagnosis and counseling or intervention as possible while the infant and family is engaged in the medical system. Further data are needed to determine the frequency of CMV-related hearing loss in infants as part of the calculation of whether CMV screening merits inclusion in a newborn hearing screening algorithm. This exact data is currently being collected in a large scale, multicenter study funded by the National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD) that seeks to enroll 100,000 infants that will be screened for congenital CMV infection (http://www.nidcd.nih.gov/health/inside/spr06/pg3.htm
). This information will become increasingly pertinent as more efficient and cost-effective methodologies for CMV screening are developed. A later potential benefit of congenital CMV screening would also be the identification of those children who are at elevated risk for later onset hearing loss due to CMV infection. By age 6 years, 6 per 1000 children will display a permanent hearing loss. At the present time, our knowledge of who is at higher risk for later onset hearing loss is minimal and identification of those children is difficult or often delayed.
It is completely tenable to foresee further expanding this hybrid screening concept to include molecular screening methodologies that could analogously utilize either Guthrie card bloodspots or simple buccal brushings that provide adequate DNA samples for mutation screening. With the ever increasing availability and utilization of molecular genetic testing for deafness causing mutations, it is plausible to envision a molecular screening process that utilizes rapid PCR assays to detect common mutations (e.g. 35delG of GJB2). With reports of GJB2 mutations being responsible for anywhere from24–40% of pediatric patients with a confirmed SNHL 49–51
, it would be reasonable to suggest incorporating a limited and rapid molecular screening for hearing loss mutations in an innovative UNHS protocol.
An inescapable aspect of such molecular or CMV screening, and indeed, all NHS methodologies, is the cost factor. With most births being covered by a capitated reimbursement system and no additional reimbursement being provided for NHS, minimizing costs to the birthing facility is essential 20, 52–58
. The cost of molecular diagnostics have the potential to gradually decrease as robotic PCR and automated sequencing systems are implemented that allow higher throughput of samples with less manpower utilization and some economies of scale. However, interpretation of molecular diagnostics remain a key feature that necessarily involves greater manpower time, effort and expertise. In the case of CMV screening at birth, work on refining different assays such as PCR of viral sequences, rapid microcultures, or routine viral cultures, will determine how cost-effective viral screenings may become.