New technologies in newborn screening.

In our Supplemental Newborn Screening Program in western Pennsylvania, we have introduced not only a unique approach to newborn screening, but also some innovative concepts in follow-up confirmation and prognostic diagnosis. The Pennsyl-vania Department of Health routinely screens only for phenylketonuria and congenital hypothyroidism. In an attempt to extend this basic state-mandated screening program, we developed, in 1986, the concept of an independent supplemental fee-for-service screening program. At present we are screening 37 hospitals plus a number of nurse midwifery programs in western Pennsylvania and eastern Ohio. We routinely screen for 11 inherited metabolic disorders: sickle-cell disease, congenital adrenal hyperplasia, galactosemia, biotinidase deficiency, maple syrup urine disease, homocystinuria, cystic fibrosis, Duchenne muscular dystrophy, glucose-6-phosphate dehydrogenase deficiency, pyroglutamic aciduria, and arginase deficiency. Having the opportunity to design our program from the start has permitted us to include screening for conditions with extensive worldwide experience and acceptance, as well as for lesser-known and less widely accepted conditions. It has also allowed us to develop and introduce some exciting new technologies as part of our routine confirmation procedures. Newborn screening for cystic fibrosis (CF), using immunoreactive trypsinogen (IRT), was first introduced in New Zealand over ten years ago [1]. Today, well over 3.2 million newborns have been screened worldwide, using this procedure [2]. In the United States, screening is only being done in Colorado, Wisconsin, at 13 hospitals in Conneticut, and by our program. A major justification for newborn screening for CF has been that at least half of the patients with CF go undiagnosed during the first year of life, while 25 percent remain undiagnosed by the end of their second year. In addition, a number of clinical benefits have been shown to be associated with early diagnosis and early treatment [3-5]. One limitation of newborn CF screening using IRT is the age-dependence of the elevation. By three to six months of age, the pancreas has begun to burn out or has, in fact, already burned out, with the result that reliable screening and retesting is limited to the early weeks or months of life; that circumstance requires a declining cutoff with increasing age. This complexity potentially increases the risk of false-negatives. A second problem with newborn IRT screening is a higher than comfortable false-positive rate. Depending on the program, between two and ten patients are referred for sweat testing in order to confirm one case of CF. While this number is …