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Improved Algorithm for Cystic Fibrosis Screening in the State of New Jersey

Newborn Screening

M. Kam, C. Russo, M. Schachter, M. Carayannopoulos

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Study

Act

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Project Aim�(Plan)

Improve the Cystic Fibrosis screening algorithm in the State of New Jersey by lowering the immunoreactive trypsinogen cutoff (IRT) to improve the first-tier screen, and subsequently increasing the number of variants screened to improve the second-tier test. In a stepwise fashion, we expect to reduce the number of false-negative screening results.

Changes We Made (Do)

To improve the sensitivity of the first-tier screen for cystic fibrosis (CF), the immunoreactive trypsinogen (IRT) cutoff was lowered from ≥ 90 ng/mL to ≥ 70 ng/mL (began April 2, 2018)

To improve the sensitivity of the second-tier screen, we increased the number of mutations screened from 1(Δ F508 only) to 139 using next-generation sequencing technology from Illumina (began July 27, 2022)

Results�Phase 1 (Lowering IRT)

Confirmed cases that would have been missed

Results�Phase 2 (Implementation of CF-139 Variant Assay)

Cases that would have been missed

Remaining Phase 2 Cases

Why it Matters

In general, it is imperative to improve processes where there is a significant quantity of false positives or negatives.

Commitment to saving babies, protecting lives: Improving the CF screening algorithm was important because we were missing newborns with the previous screening algorithm (kids that should have been screened positive were missed).

Screening for this disorder in the newborn period is crucial, as early diagnosis and treatment of patients with cystic fibrosis prevents disease associated morbidity and mortality.

Impacts & Lessons Learned

New Jersey’s screening algorithm was adjusted to meet national standards and resulted in the identification of 7 cases that would have been missed with the former screening algorithm.

Implementation of the CF 139-Variant Assay has increased the sensitivity of identifying carriers for the disease. We were able to identify 47 carriers, which is beneficial for diagnosis within families.

This change was important because it changed the trajectory of our CF screening methodology, which allowed us to identify cases that would have been missed. These babies were referred faster and provided the treatment/care that they need.

Next Steps (Act)

Although we made improvements to our screening algorithm, there is still some insensitivity associated with the IRT cutoff; due to this insensitivity, we will be moving to a floating cutoff.

Reasoning for a floating cutoff: controls for variability in IRT levels based on the time of year/changes in season, as well as assay variability

The NBS lab will continue to apply QI to our work activities by evaluating screening outcomes and assessing ways that we can better optimize current and future screening algorithms.

Can this QI project be replicated?

Replication of this project is possible by evaluating current procedures and protocols and comparing to national guidelines

Assessing current protocols and methodologies to find ways to improve and optimize outcomes can be done in any workflow to maximize efficiency