Five Years of Experience With Biochemical Cystic Fibrosis Newborn Screening Based on IRT/PAP in Germany

摘要

Background: Evidence from recent studies suggests that IRT/PAP protocols may be successfully used as a purely biochemical newborn screening (NBS) for cystic fibrosis (CF) that does not require genetic screening. However, the experience with the performance of different IRT/PAP protocols remains limited. In this study, we evaluated the performance of IRT/PAP-based CF-NBS used in two German regions between 2008 and 2013 in a large cohort. Methods: In both regions slightly different IRT/PAP protocols were used to screen newborns for CF. In contrast to the original IRT/PAP protocol published by Sarles et al., both German protocols contained an IRT-dependent safety net strategy (CF-NBS positive, if IRT >= 99.9th percentile). Positive rating of the screening result led to confirmatory diagnostics using sweat chloride testing and clinical assessment. Findings: A total of 328,181 newborns were tested with IRT/PAP in Germany within 5 years. 639 of these newborns (0.19%) were tested positive, and 60 infants were diagnosed with CF leading to a sensitivity of 0.968 and a PPV (positive predictive value) of 0.097. Compared to IRT/DNA protocols, the PPV of IRT/PAP is lower, but PAP used as second tier test has the advantage of a lower detection rate of healthy carriers and CF patients with equivocal results. Conclusions: Our results obtained in a large cohort of similar to 330,000 newborns support the use of a purely biochemical IRT/PAP protocol as an acceptable alternative when genetic CF-NBS has to be avoided. (C) 2015 Wiley Periodicals, Inc.