Immunoreactive trypsinogen screening for cystic fibrosis: Characterization of infants with a false‐positive screening test

TLDR

Newborn screening for cystic fibrosis uses elevated blood immunoreactive trypsinogen (IRT), but the benefits of early diagnosis and the test’s sensitivity, specificity, and temporal decline remain incompletely characterized. This study characterizes infants with false‑positive IRT results and investigates whether perinatal stress, as reflected by low Apgar scores, is associated with elevated IRT. The authors evaluated Apgar scores at 1 and 5 minutes in 87,000 screened infants to assess the relationship between perinatal stress and IRT levels. Among 87,000 infants, 92 had elevated IRT, 13 were confirmed CF, and 79 were false positives; false‑positive infants had significantly lower Apgar scores, yet most had normal scores.

Abstract

Abstract Blood immunoreactive trypsinogen (IRT) is elevated in newborns with cystic fibrosis (CF) and has been used as a neonatal screening test. However, not only is the benefit of early diagnosis unknown, but also the sensitivity, specificity, and time related decline of IRT values have yet to be comprehensively evaluated. This report describes the characteristics of infants with a false‐positive IRT in our experience with CF screening of 87,000 infants. The IRT value was elevated in 92 newborns; 13 had a confirmed diagnosis of CF by quantitative pilocarpine iontophoresis sweat testing, and 79 infants did not have CF and were therefore classified as false positives by IRT screening. In order to test the hypothesis that perinatal stress factors are associated with high neonatal IRT values, we evaluated Apgar scores at 1 and 5 minutes. We found that the scores of false‐positive infants were significantly lower (P = 0.0004 and P = 0.0102 at 1 and 5 minutes, respectively), compared with infants in the general population. While perinatal asphyxia as reflected by low Apgar scores is an associated factor accounting for an elevated IRT value, the majority of non‐CF newborns with an elevated IRT have normal Apgar scores.