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Newborn screening for cystic fibrosis is complicated by age-related decline in immunoreactive trypsinogen levels. M.J. Rock, E.H. Mischler, P.M. Farrell, L.-J. Wei, W.T. Bruns, D.J. Hassemer, R.H. Laessig (Wisconsin, USA). Pediatrics 1990;85:1001-1007.

Detection of elevated levels of immunoreactive trypsinogen (IRT) in dried neonatal blood spots has been used as a screening test for cystic fibrosis. In other cystic fibrosis newborn-screening studies, a sweat chloride test is generally performed only if an infant has a persistent IRT level above a selected cutoff value on both the initial and subsequent specimens. Neither the timing of the second specimen nor the value of the cutoff point for the second specimen has been comprehensively evaluated. In this randomized controlled study, 145,024 infants were screened in the neonatal period for cystic fibrosis using the 99.8% (180 ng/ml) as the neonatal cutoff point. A total of 129 infants had elevated neonatal IRT levels and had negative results on sweat tests (false-positive by IRT screening). A total of 54 children with cystic fibrosis were identified in the screened and comparison groups. Excluding patients with meconium ileus, 4 infants with cystic fibrosis had neonatal IRT values less than 180 ng/ml, and an additional 9 infants with cystic fibrosis had values decline to less than 180 ng/ml within the first 2 months of age. The IRT values of infants with and without cystic fibrosis overlapped considerably beyond 30 days of age. These findings suggest that further refinement of cystic fibrosis screening methodology will be necessary to achieve an acceptable sensitivity and specificity.

Neonatal cystic fibrosis screening: New trends. 0. Peres, M.L. Briard, F. Lemon- nier, C. Pasquet-Ferre, C. Blandin, G. Travert, Y. Fernandez (Caen, France). Archives Francaises de Pediatrie 1990:47:251-253.

Cystic fibrosis (CF) screening by means of immunoreactive trypsin (IRT) lacks specificity: only 1 out of 12 hypertrypsinemic neonates has cystic fibrosis. We propose here to analyze the KM. 19 polymorphic site in the dried blood spots as an additional test in hypertrypsinemic neonates. A blind retrospective study of 114 hypertrypsi- nemic samples has been performed after polymerase chain reaction. Twenty-seven of 37 CF (74%) were homozygous for allele 2 (2-2) and could have been diagnosed on the 15th day of life. Fifty-five percent of the infants tested were homozygous for allele 1 (l-l), a very rare feature in CF, conferring them a probability of being normal of 99.8%. At the moment, this test could be of great help in the CF screening, even better than the search for the AF508 mutation for which 45.9% of CF patients are homozygous.

Screening for cystic fibrosis: Feasibility of molecular genetic analysis of dried blood specimens W.K. Seltzer, F. Accurso, M.Z. Fall, A.J. VanRiper, M. Descartes, Y. Huang, E.R.B. McCabe (Colorado and Texas, USA). Biochemical Medicine and Metabolic Biology 1991;46:105-109.

Direct genotypic analysis for the common Caucasian cystic fibrosis mutation (AF508) was performed using dried blood specimens in a filter paper matrix (neonatal screening blotter). DNA was obtained from dried and liquid blood samples, ampli- fied, and analyzed by polyacrylamide gel electrophoresis. Additionally, intact 4-mm-