The Neonatal Detection of Cystic Fibrosis by Measurement of Immunoreactive Trypsin in Blood

Although enzymically active trypsin is not present in blood, a very small amount of the zymogen secreted by the endocrine pancreas appears to enter the circulation directly and is normally detectable in the blood by immunoassay (immunoreactive trypsin, lRT). An early stage of the exocrine pancreatic pathology in newborn infants affected by cystic fibrosis (CF) results in greater than normal amounts of IRT entering the circulation, and this occurs whether or not there are clinical symptoms and signs of the disease. For this reason measurement of IRT in whole blood spots has been proposed as a method for the detection of CF through newborn population screening. During the past decade the performance of this test has been evaluated in several population screening trials; this review describes the assays used and the results obtained. The screening strategy generally adopted is aimed at identifying infants who have prolonged neonatal hypertrypsinaemia, who are then sweat tested to confirm the diagnosis. With fairly few exceptions these trials have succeeded in detecting 91-981170 of affected infants following repeat IRT testing of 0'3-0·7% of the population initially screened, with a predictive value for CF in infants with positive repeat tests of 52-86%. Factors which are the most likely contributors to false negative and false positive results are discussed in detail. Other aspects reviewed include: the use of blood spot IRT measurement in the