NEONATAL SCREENING FOR CYSTIC-FIBROSIS - A COMPARISON OF 2 STRATEGIESFOR CASE DETECTION IN 1.2-MILLION BABIES

Objectives: To review the overall performance of a neonatal screening program for cystic fibrosis (CF) from 1981 to 1994, and to compare two strategies of case detection. Program design: Initially, immunoreacti ve trypsin (IRT) was measured in dried blood spots, and because of the low sensitivity of this test at days 3 to 5, a second sample was need ed from babies with positive test results. Since 1993 a positive IRT a ssay result has been followed by direct gene analysis for the common C F mutation, Delta F508, with the use of the same sample. Cases with fa lse-negative results were actively sought throughout the period. Resul ts: With IRT alone, 1,015,000 babies were tested. Of 389 babies with C F, 30 had a clinical diagnosis of CF made after a negative screening t est result or an administrative error. Early diagnosis was achieved in 92%. With the IRT/DNA protocol, 59 of 62 infants had a positive scree ning test result (44 were homozygous for Delta F508) among 189,000 bab ies tested. Three babies with CF had no copy of this mutation, but two were identified early because of meconium ileus. The false-positive r ate was much greater for IRT alone than for the IRT/DNA test (0.69% vs 0.054%). All false-positive cases in the IRT/DNA protocol were, of ne cessity, CF carriers. Conclusion: The percentage of babies with CF who had an early diagnosis was similar with the two protocols, but we con cluded that the advantages of the IRT/DNA test for screening, particul arly in the avoidance of the need for second IRT samples, outweighed t he drawback of unwanted carrier detection.