Blue, ElizabethBridges, Gracia2025-10-022025-10-022025-10-022025-10-022025Bridges_washington_0250O_28595.pdfhttps://hdl.handle.net/1773/54116Thesis (Master's)--University of Washington, 2025Cystic fibrosis (CF) has been universally included in newborn screening (NBS) programs across the United States for nearly two decades. In Washington State, CF NBS was introduced in 2006 and follows a two-step protocol: initial immunoreactive trypsinogen (IRT) measurement, followed by limited CFTR variant analysis for samples exceeding an IRT threshold. Studies from multiple regions and countries have shown that CF NBS is associated with improved early outcomes, including enhanced nutritional status, delayed chronic Pseudomonas aeruginosa infection, and expedited lung function growth1. However, inequities persist, with Black/African American and Asian infants experiencing false-negative screens at disproportionately higher rates than non-Hispanic White infants2. Although false-negatives are an inherent risk of biomarker-based screening, their disproportionate burden raises concerns about systemic bias within existing NBS algorithms. To explore longitudinal clinical impacts of false-negative NBS, we conducted a pilot project assessing long-term clinical outcomes among children diagnosed with CF after false-negative NBS in WA State compared to matched peers diagnosed after positive screens. We conducted a retrospective matched case-control study of individuals born between 2006 and 2024 in WA State and followed at Seattle Children's Hospital CF Center. Cases were diagnosed after a false-negative NBS; controls were matched 1:1 by birth year (±1 year) and pancreatic sufficiency status. Data collected included demographics (birth month/year, race/ethnicity, zip code), newborn screen and diagnostic characteristics (NBS IRT level and CF variant panel results, diagnosis month/year, CFTR genotype, clinical presentation, hospitalization status at diagnosis), and longitudinal clinical outcomes (height and weight percentiles, forced expiratory volume in one second (FEV1) from spirometry). Additional indicators included number and duration of hospitalizations and age at first positive Pseudomonas aeruginosa culture. Prior analyses have suggested that individuals diagnosed with CF after a false-negative NBS may experience less favorable outcomes than matched peers, including lower weight trajectories and higher hospitalization rates.1,3,4 Our results mirrored these patterns. False-negative cases were more racially and ethnically diverse (36.3% vs. 0%, p = 0.027), diagnosed later (median 19 vs. 1 month, p < 0.0001), and more often hospitalized at diagnosis (36.4% vs. 0%, p = 0.045). They also had higher annualized hospitalization rates (p = 0.018) and significantly slower growth trajectories. These findings suggest that false-negative NBS results may delay diagnosis and contribute to worse clinical outcomes, reinforcing concerns about equity in current screening algorithms.application/pdfen-USnoneCystic FibrosisFalse negativeGenetic epidemiologyHealth disparitiesIRTNewborn ScreeningPublic healthGeneticsMedicinePublic health geneticsThesis