Newborn Screening for Cystic Fibrosis and Its Incidence at a Tertiary Care Center in Saudi Arabia: A Retrospective Study

Abstract

Background: Cystic fibrosis (CF) is a life-limiting genetic disorder where early detection via newborn screening (NBS) significantly improves clinical outcomes. Data regarding CF incidence and NBS efficacy in Saudi Arabia remain limited. This single-center pilot study aimed to evaluate the primary diagnostic performance, local incidence, and CFTR genotype distribution using an immunoreactive trypsinogen (IRT)-IRT NBS protocol implemented exclusively at our institution, Prince Sultan Military Medical City (PSMMC), Riyadh. Methods: A retrospective analysis was conducted on 10,286 newborns screened. between May 2017 and April 2019 using a two-tiered IRT sequence (Day 1 and Day 5). Screen-positive infants underwent confirmatory sweat conductivity analysis and CFTR variant testing. Results: Three infants were confirmed with CF, yielding a regional incidence of 1:3,429 live births (2.9 per 10,000). Day 5 IRT levels were significantly higher in confirmed CF cases than in non-CF infants (136.07 ± 27.24 vs. 19.44 ± 13.08 ng/mL, p = 0.003) and strongly correlated with sweat conductivity (r = 0.698, p < 0.001). Receiver operating characteristic (ROC) analysis identified an optimal Day 5 IRT cutoff of 114.9 ng/mL (area under the ROC curve (AUC)= 0.999), demonstrating 75.0% sensitivity and 99.8% specificity. Genetic confirmation identified three distinct homozygous variants (c.1416delG, I1234V, and c.1418delG). Conclusion: This descriptive pilot study conducted at our center demonstrates the feasibility and diagnostic utility of the IRT-IRT screening protocol for early CF detection. To build upon these single-center findings and support the development of a comprehensive national screening strategy, future multi-center studies across Saudi Arabia are recommended.