Evaluating the efficacy of IRT-based newborn screening for cystic fibrosis in a Turkish tertiary care center

Cystic fibrosis (CF) is a genetic disorder associated with multiorgan dysfunction. It has been included in the newborn screening program in Turkey since 2015. Our aim is to re-evaluate patients with IRT (immunoreactive trypsinogen) positivity, to identify cases missed through our screening process, and to obtain information about the positive predictive value and sensitivity of the IRT screening program. We identified 208 infants referred to our center between 2015 and 2023 due to IRT positivity. Infants were categorized into four groups based on guidelines: CF, CRMS (Cystic Fibrosis Related Metabolic Syndrome), carrier, and false-positive newborn screening test. Clinical data, IRT and SCT values, and genetic analysis were reviewed. 29.3% were diagnosed with CF, 5.7% had CRMS, and 15.3% were carriers. 7 CF patients were identified through genetic analysis despite normal SCT values. Significant differences were found between the CF group and other groups concerning mean IRT values. At the threshold value of 100.1 ng/mL for IRT-1, the sensitivity was 83% and the specificity was 37%. Meanwhile, for the threshold value of 97.2 ng/mL for IRT-2, sensitivity was 89% and specificity was 19%. The positive predictive value with these thresholds was determined to be 60%. SCT is insufficient as a stand-alone test for the CF diagnosis. A comprehensive diagnostic protocol, including SCT and genetic analysis, is needed. Our findings underscore the importance of genetic testing. The high false-positivity of our screening strategy suggests that the IRT thresholds in use are low. This study advocates for a reassessment of these threshold values to improve the screening system’s precision.