IN A significant development for U.S. healthcare, new consensus guidelines from the Cystic Fibrosis Foundation call for a nationwide overhaul of newborn screening protocols for cystic fibrosis (CF). These recommendations, rooted in systematic evidence reviews, aim to enhance diagnostic timeliness, sensitivity, and equity, addressing long-standing disparities and inefficiencies in current state-run programs.
Cystic fibrosis newborn screening has been universal in the U.S. since 2010, but protocols vary widely by state. The new seven-part guideline focuses on refining the screening algorithms, particularly the use of immunoreactive trypsinogen (IRT) cutoffs and CFTR genetic testing.
One key change is the recommendation to replace fixed IRT thresholds with floating cutoffs, a move designed to better capture infants at risk regardless of seasonal or laboratory variability. Additionally, states that use variant panels with less than 95% sensitivity across ancestral groups are advised to implement a “very high IRT” referral strategy to prevent missed diagnoses in non-European populations.
The guideline also pushes for comprehensive CFTR variant detection, moving beyond the commonly used F508del variant and the limited 23-variant panel recommended by the American College of Medical Genetics. Instead, the use of full CFTR2 variant panels, which now include over 1,000 CF-causing mutations—is strongly encouraged.
Notably, the guidance promotes more frequent CFTR variant screening, recommending labs process results at least twice weekly. It also introduces a three-tiered testing strategy: beginning with IRT measurement, followed by a variant panel, and concluding with CFTR gene sequencing when needed. This approach, known as IRT-DNA-SEQ, aims to boost the specificity and predictive value of screenings.
Finally, both primary care physicians and CF specialists should be promptly notified of abnormal results to ensure timely intervention.
The Foundation anticipates that full implementation of these updates will not only accelerate diagnosis but also reduce disparities and improve long-term outcomes for children born with CF. As genetic technologies advance and become more accessible, these new guidelines signal a pivotal shift toward more equitable and effective care from the very first days of life.
Reference: McGarry Me et al. Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation. Int J Neonatal Screen. 2025;11(2):24.
