DNA Testing of Blood Sample Not Effective for Identifying CMV in Newborns, Says UAB Research
CMV is the most common infection passed from a mother to her unborn child. About 20,000-30,000 infants are born infected with CMV each year, and 10 to15 percent of those risk hearing loss. The sooner doctors can identify CMV infection, the better they can monitor a child's hearing.
Because dried blood spots routinely are collected from all infants born in the United States for screening for metabolic and genetic disorders, there has been considerable interest in using polymerase chain re­action (PCR)-based methods for detecting CMV in new­borns' specimens. Current rapid-culture CMV testing is a highly effective procedure that uses saliva or urine instead of dried blood samples to make the identification. The rapid-culture method is labor-intensive and requires an on-site tissue-culture facility, which makes it difficult to adapt this technology for widespread screening.
The lead author and co-principal investigator Suresh B. Boppana, M.D., professor of medicine in the Division of Pediatric Infectious Diseases at UAB, and colleagues compared the two. They found that dried blood sample real-time PCR testing had low sensitivity and did not identify approximately two-thirds of the congenital CMV infections when compared with saliva rapid culture,
"To identify these at-risk infants early in life, rapid, reliable, and relatively inexpensive methods to screen newborns for congenital CMV infection are needed," Boppana said. "Early identification of at-risk children will allow targeted monitoring in order to intervene at criti­cal stages of acquiring speech and lan­guage skills. Unfortunately, at least with current technologies, these findings show us that the heel-stick test is not an option for a primary newborn screening tool for CMV."
Previous studies have found that dried blood-spot PCR is able to identify babies with congenital CMV infection, so some researchers have suggested that it be used for a universal screening program. However, none of the earlier studies compared dried blood spot PCR results to rapid culture, and therefore could not determine if the PCR procedure was as good as the standard method, missed infected babies or falsely identified babies as being CMV-infected when they were not.
For this study, 20,448 babies were screened, 92 of whom were confirmed to have congenital CMV infection. The rapid culture method identified 91 of the 92 infants, for nearly 100 percent sensitivity. For the 11,422 infants who were screened using a single primer PCR analysis from dried blood spots, only 17 out of 60 infected children were identified, a 28.3 percent sensitivity. Of the 9,026 infants who were screened with the two-primer PCR method, 11 out of 32 infected children were identified, a sensitivity of 34.4 percent.
"In order to be included as part of a screening test, the minimum sensitivity should be at least 95 percent," Boppana said. "Our findings indicate that dried blood-spot PCR will only detect 30-40 percent of babies with CMV infection. More than half of babies who are infected would be missed."
The researchers now are assessing whether analysis of saliva samples using real-time PCR technology can do a better job than dried blood spots when compared with the rapid culture method. They believe that the use of saliva may be beneficial since babies with congenital CMV infection are known to have a lot of virus in their saliva, compared to the blood, where amounts can vary depending on when the infant was infected during development. In addition, saliva samples require minimal processing and are noninvasive.
"These results have major public-health implications because they indicate that such methods, as currently per­formed, will not be suitable for the mass screening of newborns for congenital CMV infection the most common non-genetic cause of deafness in the United States," said co-principal investigator Karen Fowler, Dr.Ph., professor of medicine in the Division of Pediatric Infectious Diseases at UAB. "As the disease burden from congenital CMV infection remains a significant public-health problem, we must find a rapid, reliable and relatively inexpensive method to identify the large number of infants with clinically inapparent, congenital CMV infection early in life.
"The results of our study under­score the need for further evaluation of high-throughput methods performed on saliva or other specimens that can be adapted to large-scale newborn CMV screening," Fowler said.
The study, funded by the National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, is part of a multi-center research project headed by UAB that is seeking to find the most effective screening test for CMV infection in newborns. The standard method for detecting CMV infection in newborns is labor-intensive and not conducive to a widespread screening program.
Other participating institutions are Saint Peter's University Hospital, New Brunswick, N.J.; University of Mississippi Medical Center, Jackson; Carolinas Medical Center, Charlotte, N.C.; University of Pittsburgh and the Children's Hospital of Pittsburgh; University of Texas Southwestern Medical Center, Dallas; and University of Cincinnati and Cincinnati Children's Hospital Medical Center.
About the UAB Division of Pediatric Infectious Diseases
The UAB Division of Pediatric Infectious Diseases provides excellent outpatient and inpatient care for infants, children and adolescents diagnosed with bloodstream infections, meningitis, pneumonias, viral diseases and other infections. The division operates a state-of-the-art diagnostic virology laboratory and provides clinical leadership for antibiotic use and infection control at Children's Hospital.
Jennifer Lollar
jpark@uab.edu