This study examined for the first time to our knowledge the national data available from newborn screening programs in the United States and determined the salient characteristics of various screening tests for 3 hereditary metabolic disorders and 2 congenital endocrinopathies with emphasis on positive predictive values (PPVs) to delineate the magnitude of false-positive results.
Reports published by the Council of Regional Networks for Genetic Services for 1990 through 1994 were examined carefully, paying particular attention to phenylketonuria, galactosemia, biotinidase deficiency, congenital hypothyroidism, and congenital adrenal hyperplasia (CAH). Because of recent improvements in data collecting, reporting, and tabulating, we used data from 1993 and 1994 to determine the apparent sensitivity, specificity, relative incidence rates, and PPVs for the 5 disorders. For biotinidase deficiency and CAH, we also calculated relative incidence rates and PPVs for 1991 and 1992.
Our analyses revealed the following best estimates for the relative incidence rates of 5 disorders: phenylketonuria, 1:14,000; galactosemia, 1:59,000; biotinidase deficiency, 1:80,000; congenital hypothyroidism, 1:3300; and CAH, 1:20,000. An apparent sensitivity of 100% has been reported by the various states for most of the disorders, and specificity levels are all above 99%. The PPVs, however, range from 0.5% to 6.0%. Consequently, on average, there are more than 50 false-positive results for every true-positive result identified through newborn screening in the United States.
The magnitude of false-positive results generated in newborn screening programs, particularly for congenital endocrinopathies, presents a great challenge for future improvement of this important public health program. Attention must be given to improved laboratory tests, use of more specific markers, and better risk communication for families of patients with false-positive test results.