Cytomegalovirus (CMV) is the most common congenital viral infection in the United States, affecting approximately 0.7% of all newborns, of which an estimated 90% will be asymptomatic at birth [1-4]. It is estimated that up to 0.2% of U.S. infants have signs and symptoms of congenital CMV infection at birth, based on retrospective analyses of infants diagnosed with congenital CMV [3]. Recognizing congenital CMV disease in the neonatal period can be challenging since manifestations such as microcephaly, chorioretinitis, and thrombocytopenia are not unique to CMV infection [5-7]. Consequently, few infants with even symptomatic congenital CMV are likely to receive a diagnosis in the absence of screening. Because 40-58% of surviving infants with congenital CMV infections that are symptomatic at birth will develop permanent sequelae [2], diagnosis of congenital CMV disease in the newborn period is important for identifying those with neurologic abnormalities who may benefit from treatment with antivirals as well as those who will need ongoing management of CMV-related sequelae such as hearing and vision loss.

Up to 12% of infants with congenital CMV infection that are asymptomatic at birth will develop CMV-related hearing loss later in childhood [2]. Routine newborn screening for congenital CMV infection is not currently recommended; rates of laboratory testing for congenital CMV infection and ascertainment of congenital CMV disease in the United States are unknown. Congenital CMV infection is confirmed by detection of CMV DNA by PCR or CMV by viral culture from urine, saliva, or blood [8]. In order to distinguish between congenital and postnatal infection, testing should be conducted within the first 2–3 weeks after birth [9] as infants may acquire CMV from infected cervical and vaginal secretions during delivery, breast milk feeding, or blood transfusions.

The objective of this study was to determine, in the absence of recommendations for routine screening for congenital CMV infection or disease, rates of coding for CMV diagnosis and testing among insured infants less than one month of age in the United States using a large national healthcare claims database.

This is the first study to examine the frequencies of diagnostic coding for congenital CMV and CMV laboratory testing among infants ≤1 month of age using healthcare claims data from a large insured population in the United States. We found that CMV-specific testing is rarely coded for infants and most CMV-specific testing appears to have been conducted for diagnostic purposes since 82% of those tested had a claim for at least one potential manifestation of congenital CMV disease. We found that 44% of CMV-specific testing conducted among infants ≤1 month of age appeared to be limited to serologic assays. Virologic testing is necessary for confirmation of congenital CMV infection because CMV IgG detected in newborns may reflect maternal antibody transmission and assays to detect CMV IgM antibodies lack sensitivity and specificity [7]. Although virologic testing was historically used as the gold-standard for diagnosing CMV, PCR testing for CMV is now widely accepted and the preferred method in some settings. While the low rates of CMV testing among infants with symptoms suggestive of congenital CMV infection and the high proportion of infants who appeared to have been tested only with serologic assays instead of PCR or viral culture may be explained in part by incomplete medical claims coding or bundling of services, these findings suggests gaps in awareness among healthcare providers of congenital CMV disease and its diagnostic evaluation.

We identified 0.02% of infants ≤ 1 month of age as having congenital CMV infection or CMV disease in a privately-insured population using healthcare claims data. That is a small percentage of the true rate of congenital CMV infection in the US population. The low rate of diagnosis of congenital CMV disease that we report likely reflects a combination of the insensivity of claims data in general to detect all diagnoses and tests included in medical records, and the low rate of clinical diagnosis of congenital CMV which could reflect low awareness among healthcare providers of congenital CMV disease as well as the non-specific nature of symptoms. Although healthcare claims databases are not sensitive enough to identify all symptomatic congenital CMV infections in the United States, they may be useful for surveillance to monitor trends in testing practices and diagnostic coding for congenital CMV disease in the absence of national surveillance for congenital CMV infection or disease.

An additional factor that might help account for the low frequency of diagnoses of congenital CMV in the present study is the selective nature of the MarketScan population, which represents individuals with employer-sponsored health insurance, about 55% of the US population in 2011 [11]. People with employer-sponsored insurance are less likely to be low-income or non-white than are uninsured or publicly-insured people [12]. Future work could examine the frequencies of coding for CMV diagnosis and CMV testing rates in the US population with publicly-financed health insurance.

There are a number of challenges to using claims data to investigate laboratory testing for congenital CMV infection. We were only able to identify infants with a diagnostic code for CMV infection, but were unable to confirm congenital CMV infection without access to laboratory test results or medical record review. The proportion of infants with CMV testing is likely underestimated as there is no specific billing code for CMV-specific viral culture. However, even if some of the claims for non-specific viral or molecular testing actually represented CMV-specific testing, the rate of CMV testing would still be quite low. It is unclear the extent to which CMV diagnostic testing was performed but not billed for with individual test codes; our finding that only 10% of infants had a code for one of the other routinely performed laboratory tests, suggests that there may be additional testing occurring that is not detectable because of bundling of charges. Many of the conditions associated with congenital CMV disease, such as jaundice, low birth weight, and hearing loss, are non-specific and have numerous potential underlying etiologies. It is difficult to definitively determine from medical claims data whether these conditions were due to congenital CMV infection but not recognized by providers as being CMV-related, coded to indicate an evaluation rather than diagnosis of CMV, or if an alternative etiology was identified. Some signs of symptomatic congenital CMV infection, such as petechiae and hepatosplenomegaly, are unlikely to be coded in claims data, even if recognized and recorded in the medical record. Finally, we were unable to validate the sensitivity and specificity of codes for CMV testing and diagnosis using medical claims. In the future, it would be useful to conduct a validation study of coding to enhance the interpretability of claims data for CMV testing and diagnostic coding.

This study provides data on testing practices for congenital CMV infection among a sample of privately-insured infants in the United States. The substantial proportion of infants tested with only serologic assays instead of PCR or viral culture suggests gaps in knowledge of laboratory confirmation of CMV infection. Further investigation of the low prevalence of diagnosed symptomatic congenital CMV disease detected in this population merits further research to understand the true burden and spectrum of congenital CMV disease in this population, the extent to which symptomatic congenital CMV disease may go undiagnosed, and the validity of medical claims data for identifying this condition whether claims data could be an adequate source for surveillance to monitor trends in CMV testing and diagnostic coding in the United States. As the indications for and benefits of antiviral treatment for congenital CMV disease in early infancy are refined, increasing awareness and prompt ascertainment of congenital CMV is important to ensure identification of all infants who might benefit from early treatment.

CMV: Cytomegalovirus; ICD-9-CM: International Classification of Diseases, 9^th revision, Clinical Modification; CPT: Current Procedural Terminology; PCR: Polymerase chain reaction; IgG: Immunoglobulin G; IgM: Immunoglobulin M; DFA: Direct fluorescent antibody; EIA: Enzyme immunoassay.

The authors declare that they have no competing interests.

JL conceptualized and designed the study; acquired, analyzed, and interpreted the data; drafted and critically revised the manuscript for important intellectual content; and approved the final manuscript as submitted. MJC conceptualized and designed the study; interpreted the data; reviewed and critically revised the manuscript for important intellectual content; and approved the final manuscript as submitted. SDG conceptualized and designed the study; interpreted the data; reviewed and critically revised the manuscript for important intellectual content; and approved the final manuscript as submitted. SRB conceptualized and designed the study; interpreted the data; reviewed and critically revised the manuscript for important intellectual content; and approved the final manuscript as submitted.

No additional information to add.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-2431/13/90/prepub