Evaluating Georgia's Cystic Fibrosis Newborn Screening Algorithm to Inform Improvement Recommendations
Brittany Truitt1,2, Eileen Barr2,3, Angela Wittenauer3
1Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
Insights
Newborn screening for cystic fibrosis (CF) in Georgia has false negatives, particularly impacting minority infants. Expanding genetic testing could improve early detection and outcomes for children with CF.
Area of Science:
- Medical Genetics
- Newborn Screening
- Pediatric Pulmonology
Background:
- Early diagnosis of cystic fibrosis (CF) through newborn screening (NBS) significantly improves patient outcomes.
- Georgia utilizes a two-tiered NBS algorithm involving immunoreactive trypsinogen (IRT) and a 39-variant *CFTR* genetic panel.
Purpose of the Study:
- To evaluate the frequency of false-negative NBS results in children with CF (CwCF) in Georgia.
- To identify factors contributing to delayed CF diagnoses beyond 28 days of age.
- To assess the impact of race and ethnicity on missed or delayed diagnoses.
Main Methods:
- Retrospective review of CwCF born in Georgia between 2007 and 2022.
- Analysis of NBS data, including IRT levels and *CFTR* variant detection.
- Characterization of cases with delayed diagnoses and examination of demographic disparities.
Main Results:
- Of 390 CwCF, 4.6% had false-negative NBS results due to lack of *CFTR* variant detection or low IRT.
- Thirty children experienced delayed diagnoses, often linked to sweat testing.
- Minoiritized infants, particularly Black and Hispanic infants, faced significantly higher odds of missed or delayed diagnoses.
Conclusions:
- Current NBS protocols in Georgia can result in missed or delayed CF diagnoses.
- Disparities in diagnosis rates exist among different racial and ethnic groups.
- Expanding *CFTR* variant assays and refining NBS protocols are recommended to improve early detection and reduce diagnostic delays.
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.
