(153) Improving consistency of work-up for infants with positive NBS and inconclusive diagnosis

Background: Newborn screening (NBS) for cystic fibrosis (CF) has led to a rise in the number of infants with positive NBS but inconclusive diagnosis. Despite the availability of guidelines for the work-up and management of infants with suspected CFTR-related metabolic syndrome (CRMS), rapid advances in genetic testing have resulted in variation in practice at our center. To address these discrepancies, the Children’s Healthcare of Atlanta and Emory University Pediatric CF Program started a quality initiative aimed to establish an institutional guideline for infants with positive CF NBS, intermediate sweat test, and uncertain genetic testing.

Methods: A 6 question survey about management of infants with inconclusive diagnoses was sent out to all pediatric CF providers. The survey consisted of 3 multiple choice questions, and 2 multi-step diagnostic scenario questions.

Results: Survey data identified discrepancies in provider work-up for infants with positive NBS and intermediate sweat test. Some providers preferred to wait for repeat sweat test, while others chose to pursue genetic testing immediately. Results were reviewed at a clinic-wide QI meeting. Key cases were discussed, including 1) an infant found to have 2 CFTR variants whose sweat test normalized by 2 months and thus could have been falsely cleared as a carrier without early sequencing and 2) an infant whose sequencing was delayed and was eligible to start ivacaftor before testing resulted. A guideline for infants with positive NBS and uncertain diagnosis was then developed to ensure consistency from all providers. The algorithm recommends CFTR sequencing and deletion/duplication testing after initial intermediate sweat test as well as a consistent follow-up schedule for CRMS patients.

Conclusions: This QI initiative aimed to optimize quality and consistency of care for infants with positive CF NBS, intermediate sweat testing, and uncertain genetic testing. We plan to follow-up after algorithm implementation to determine effectiveness. During the development process, providers noted the critical benefit of having a genetic counselor, experienced in CF, involved in the diagnostic process to assist with interpretation of genetic results and provide counseling to families.

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