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DOI: 10.1055/s-0035-1556593
Combining IRT/PAP+SN with DNA analysis for the best CF newborn screening strategy for Germany
Introduction: Evidence from recent European studies suggests that protocols using immunoreactive trypsine (IRT) and pancreatitis associated protein (PAP) for cystic fibrosis (CF) newborn screening (NBS) may be successfully used as a purely biochemical NBS strategy that does not require genetic screening. Pure IRT/PAP protocols can reach acceptable sensitivities and specificities, but this comes at the expense of a relatively low positive predictive value (PPV). The Dutch CHOPIN study (Vernooij-van Langen 2012) has reported that using a three tier strategy (IRT/PAP + extended gene analysis) results in a better PPV.
Objective: Assessment of the performance of different IRT/PAP/DNA CF NBS protocols using different numbers of CFTR mutations included in the DNA test panel.
Methods: Recent data available from the cohort of the Heidelberg CF NBS study (2008 – 2014, 354.722 newborns) were evaluated in a post hoc analysis. The IRT/PAP protocol used in Heidelberg (Sommerburg et al. 2010) used one IRT-independent PAP-cut-off and a safety net (SN, CF-NBS positive, if IRT ≥99.9th IRT percentile) to reach a sufficient sensitivity.
Findings: The combined strategy (IRT/PAP+SN/DNA) resulted in a sensitivity similar to that of IRT/PAP+SN, but a higher specificity and a higher PPV. Nevertheless, the strategy keeps main advantages of IRT/PAP, such as the detection of considerably fewer carriers and fewer newborns with CFSPID when compared with current IRT/DNA screening strategies. Using a mutation panel covering less than 80% allele frequency will lead to a loss of sensitivity when compared to the results of IRT/PAP+SN alone. A sufficient performance (sensitivity and PPV) could already be reached with a mutation panel covering the most common 20 mutations in the German population.
Conclusions: Our results obtained in a cohort of 354.722 newborns support the use of a IRT/PAP+SN/DNA protocol to achieve a better PPV compared to a purely biochemical IRT/PAP+SN protocol.
*Presenting author