Newborns are screened for CF in the United States. This leads to prompt diagnosis and initiation of therapy, which improves the quality of life. A blood sample, collected by heel prick onto filter paper, is sent to a state or regional laboratory for a variety of NBS tests. Two-tier testing for CF is employed by most states. Blood immunoreactive trypsinogen (IRT), a pancreatic enzyme, is measured in the primary screening. IRT is initially elevated in CF patients (possibly due to pancreatic inflammation) and then declines in infancy. However, IRT is increased in a variety of other conditions as well, such as neonatal apnea. Therefore, all elevated samples are reflexed to a second test on the original sample. The second test in most states is for specific DNA mutations. The ethnic makeup of the regional population determines which CFTR mutations will be tested. For more information concerning CF NBS, refer to Newborn Screening for Cystic Fibrosis; Approved Guideline. CLSI document I/LA35-A.6
If the NBS test is positive, a sweat test is performed to confirm the diagnosis. A positive DNA test may not be able to distinguish the heterozygote (carrier) state from the homozygous (affected) state. This is because a patient with one known CF-causing mutation (aka a positive result) may have a second, unidentified mutation on the other allele (therefore affected) or may have no CF-causing mutation on the other allele (carrier). Patients that have reported 2 CF-causing mutations are still referred for sweat testing to rule out specimen misidentification or the presence of both mutations on the same allele.
6. Clinical and Laboratory Standards Institute (CLSI). Newborn Screening for Cystic Fibrosis; Approved Guideline. CLSI document NBS05-A. Wayne, PA: CLSI; 2011.
