Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.
Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.
“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.
In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.
The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.
The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).
By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.
The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.
However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.
The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
Findings lay foundation for widespread use
“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.
Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.
“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.
“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.
The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.
Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.