April 19, 2010

”Heel-Stick” Test Misses Viral Cause of Hearing Loss

Photo of a newborn infant's foot held in a woman's hands

The routine "heel-stick" blood test that screens for several disorders in newborns would fail to detect most cases of cytomegalovirus (CMV) infection, a leading cause of hearing loss in children. The new finding highlights the need for rapid, reliable and cost-effective screening methods that can identify the virus early in life.

CMV is the most common infection passed from mother to unborn child. Because most infected newborns have no symptoms, CMV infection often goes undetected until later in life, when problems like hearing loss begin to emerge. Nationwide, about 20,000-30,000 infants are born each year with CMV infections, and up to 15% are at risk for eventual hearing loss.

A few studies have suggested that DNA analysis of dried blood spots, routinely collected from newborns, might be a quick and convenient alternative to the standard "rapid culture" method for detecting CMV in saliva or urine. Although the standard method is highly accurate, it's labor-intensive and relatively expensive, making it difficult to adapt for widespread screening. The newer DNA technique is known as real-time polymerase chain reaction (PCR).

Until now, no large studies have directly compared the 2 techniques. Dr. Suresh Boppana of the University of Alabama at Birmingham and colleagues undertook the comparison in a study supported by NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD).

For the PCR test, the scientists analyzed dried blood samples obtained through the routine heel-stick procedure, which involves pricking a newborn’s heel and placing small droplets of blood on filter paper for later testing. The procedure is currently used to test for several disorders, including hypothyroidism and sickle cell disease.

The results appeared in the April 14, 2010, edition of the Journal of the American Medical Association. Of the 20,448 babies screened using both techniques, 92 were confirmed to have congenital CMV infection. As expected, the standard rapid culture analysis of saliva had nearly 100% sensitivity, or accuracy. The method identified 91 of the 92 infected infants.

The researchers tried 2 different types of PCR to detect CMV in the dried blood samples. For the 11,422 infants screened with the first method, called a single-primer PCR test, the sensitivity was just over 28%, with 17 out of 60 infected children identified. The researchers hoped to increase the test’s accuracy by using a 2-primer method on the remaining 9,026 infants. But the second test was only slightly more sensitive, identifying just over one-third of the 32 infected newborns.

"In order to be included as part of a screening test, the minimum sensitivity should be at least 95%," says Boppana. "Our findings indicate that dried blood spot PCR will only detect 30-40% of babies with CMV infection. More than half of babies who are infected would be missed."

The researchers are now assessing whether real-time PCR might be more effective in detecting evidence of CMV in saliva, which is known to carry large amounts of the virus, rather than in dried blood.

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