DNA Testing of Blood Sample Not Effective for Identifying Newborns With Infection That May Cause Hearing Loss

DNA analysis of dried blood samples routinely collected from newborns did not effectively identify an infection that is a major cause of hearing loss in children, according to a study in the April 14 issue of JAMA.1

Cytomegalovirus (CMV) is an important cause of con genital infection and a lead ing cause of sensorineural hearing loss (SNHL) in children. “Of the estimated 20,000 to 40,000 infants born each year with congenital CMV infection in the United States, most (90 percent to 95 percent) have no detectable clinical abnormalities at birth and thus will not be identified by routine clinical examination,” according to background information in the article. “To identify these at-risk infants early in life, rapid, reliable, and relatively inexpensive methods to screen newborns for congenital CMV infection are needed. Identification of children at increased risk of CMV-associated SNHL early in life will allow targeted monitoring of these children in order to intervene at criti cal stages of acquiring speech and lan guage skills.”
 

Since dried blood spots (DBS) are collected routinely for newborn metabolic screenings from all infants born in the United States, there has been considerable interest in using polymerase chain re action (PCR; a technique in molecular genetics that permits the analysis of any short sequence of DNA)-based methods for detecting CMV in new born DBS specimens. “Despite the ben efits of DBS PCR-based methods, the sensitivity and specificity of these assays for universal newborn CMV screening have not been determined,” the authors write.

Suresh B. Boppana, M.D., of the University of Alabama at Birmingham, and colleagues examined the diagnostic accuracy of real-time PCR analysis of DBS as an approach for mass screening of new borns for congenital CMV infection. Between March 2007 and May 2008, infants born at 7 U.S. medical centers had saliva specimens tested by rapid culture (can be used for identification of CMV infection, but not favorable for mass screening). These results were compared with results of DBS real-time PCR tests for CMV infection.
 

Among the findings of the researchers was that compared with saliva rapid culture, CMV testing with DBS real-time PCR had low sensitivity, and did not identify approximately two-thirds of the congenital CMV infections.

“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 nongenetic cause of deafness in the United States,” the authors write. “As the disease burden from congenital CMV infection remains a significant public health problem, there contin ues to be a need to identify the large number of infants with clinically inapparent congenital CMV infection early in life. The results of our study under score 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.”
 

James F. Bale Jr., M.D., of the University of Utah School of Medicine, Salt Lake City, writes in an accompanying editorial2 that these findings do not necessarily suggest that the goal of uni versal screening for CMV should be abandoned.

“Although current tissue culture methods are too time consuming and expensive to be used for mass screening of newborns, mo lecular detection methods can provide high-throughput screening for CMV. While assaying the newborn dried blood spot may not be the solution to the problem of universal screening for congenital CMV infection, detecting viral DNA in specimens obtained in the first few days of life may still be possible. Rather than assaying blood, one possible ap proach is to consider assaying a specimen of the infant's sa liva. The saliva of virtually all congenially infected infants contains abundant quantities of CMV DNA that can be de tected by current PCR methods.”
 
References:
1. JAMA. 2010;303[14]:1375-1382.
2. JAMA. 2010;303[14]:1425-1426.