Neonatal screening for cystic fibrosis using blood trypsin with complementary meconium lactase: an advisable strategy for the population of southern Europe

Abstract

Introduction: Neonatal screening for cystic fibrosis (CF) is now included in several newborn screening programs, based on the view that early presymptomatic diagnosis and therapy for CF reduces the morbidity and mortality from that disease. However, screening for CF is complicated by a relatively high rate of false-positive and a substantial frequency of false-negative results. To reduce the rates of these aberrant results, we have developed a neonatal screening strategy that combines estimation of immunoreactive blood trypsin (IRT) with the meconium lactase activity assay (LACT) for those blood samples that produce the highest 1% of IRT. Methods: This system was used to screen 157 992 newborns in Northeastern Italy from September 1988 to August 1991. Meconium collected just after birth was smeared on filter paper and dried. Immunoreactive trypsin was measured in dried blood spots collected when the infants were 3–5 days old. If the level of IRT exceeded 30 μg/1, LACT was determined in the dried meconium sample. If LACT exceeded 0.5 U/g, a confirmatory sweat test was performed on the infant (mean age, 22 days). If LACT was negative but the IRT level exceeded 40 μg/1, a repeat filter paper blood specimen was collected for IRT measurement. If the IRT level was > 17 μg/1 in this specimen, sweat testing was performed on the infant (mean age, 40 days). Results: We found an incidence of 1:3510 for CF, with 86% of patients identified by LACT among those diagnosed by IRT screening. The initial IRT cut-off level of 30 μg/1 selected 0.83% of screened infants as positive but the complementary use of LACT reduced the rate of sweat tests or requests forrepeat specimens to 0.31%. No false-negative results were encountered, with the exception of three cases of meconium ileus. Discussion: This screening strategy seems to reduce the frequency of false-positive results, while also reducing the rate of false-negative results in neonatal screening for CF.