# Evaluating Georgia’s Cystic Fibrosis Newborn Screening Algorithm to Inform Improvement Recommendations

## TL;DR

This study evaluates Georgia's cystic fibrosis newborn screening system and finds that it misses or delays diagnoses in some infants, especially among minoritized groups.

## Contribution

The study identifies specific gaps in Georgia's newborn screening algorithm and provides data-driven recommendations for improvement.

## Key findings

- 18 out of 390 children with cystic fibrosis had false negative newborn screening results.
- Black and Hispanic infants had higher odds of missed or delayed diagnosis compared to non-Hispanic White infants.
- Expanded CFTR assays could reduce missed cases, and seasonal IRT variations suggest potential for improved cut-off approaches.

## Abstract

Early diagnosis by newborn screening (NBS) has contributed to improved outcomes in children with cystic fibrosis (CwCF). Georgia’s two-tiered algorithm consists of a fixed immunoreactive trypsinogen (IRT) cut-off followed by a 39-variant CFTR genetic panel. We conducted a retrospective review of CwCF born in Georgia from 2007 to 2022 to evaluate false negative NBS frequency. We characterized CwCF whose diagnosis was delayed beyond 28 days of age despite positive NBS. Six cases were detailed demonstrating the impact of missed and delayed diagnoses. We examined IRT trends from 2018 to 2022 and cut-off approaches. Missed case detection by expanded CFTR variant assays was assessed. Of 390 CwCF born in Georgia, 18 (4.6%) had false negative NBS—6 due to lack of CFTR variant detection and 12 due to low IRT values. Thirty children had delayed diagnosis, with the majority related to sweat testing. Minoritized children made up 19% of the population but 43% of missed and 44% of delayed diagnoses. Black and Hispanic infants had higher odds of missed or delayed diagnosis compared to non-Hispanic White infants (OR = 2.7, p = 0.027 and OR = 6.1, p < 0.001, respectively). Average IRT values varied across kits and were lower in warmer seasons. Expanded CFTR assays would reduce missed cases. Our results informed recommendations for improvement at multiple steps in the NBS process.