Clinical and Laboratory Standards Institute guideline NBS05—Newborn Screening for Cystic Fibrosis describes newborn screening (NBS) laboratory tests and screening strategies used worldwide to identify newborns at increased risk of developing cystic fibrosis (CF). CF is a common genetic disorder caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Presymptomatic detection through NBS leads to early diagnosis and improves the outcomes of babies with CF. This guideline describes comprehensively the laboratory tests for detecting CF risk among newborns as well as recommendations for follow-up evaluation. It describes the use of immunoreactive trypsinogen assays and second-tier NBS testing, including DNA analysis for detecting specific CFTR variants and pancreatitis-associated protein assays. A core panel of CFTR variants for routine testing is discussed with guidance included on NBS program considerations for core panel expansion. This guideline is intended for use by NBS laboratory, follow-up, and program personnel; public health program administrators; medical laboratories; CF center personnel and organizations responsible for CF center networks; health care providers (eg, primary care providers, neonatologists, pediatricians, disease specialists); regulatory agencies; public health policy makers; and manufacturers of instruments, reagents, and related products for NBS testing.

This guideline replaces the previous edition of the approved guideline, NBS05-A, published in 2011. Several changes were made in this edition, including: 
• Reassessed IRT cutoff value guidelines and discussed the use of a floating rather than fixed cutoff value 
• Revised recommendations regarding CFTR variant panels based on the most current information, including new biotechnologies such as next-generation sequencing 
• Assessed using PAP for detecting newborns at risk for CF 
• Discussed communication strategies related to detecting CF heterozygote newborns and providing genetic counseling 
• Reviewed emerging issues related to using genetic and genomic sequencing in NBS 
• Described the existing CF NBS algorithms

This guideline specifies recommendations for newborn screening (NBS) for cystic fibrosis (CF) and routine use of dried blood spot (DBS) specimens for identifying potentially affected newborns. This guideline also discusses the preanalytical, analytical, and postanalytical activities of CF NBS, including short-term follow-up (STFU) and long-term follow-up (LTFU) considerations. 

This guideline describes: 
• Screening methodologies for immunoreactive trypsinogen (IRT), pancreatitis-associated protein (PAP), and cystic fibrosis transmembrane conductance regulator (CFTR) gene variant analysis 
• Screening algorithms currently used, including the use of IRT assays alone or in combination with DNA analysis for detecting specific CFTR variants through second-tier NBS with the IRT/DNA strategy 
• Variations in the IRT/DNA strategy, including the use of PAP testing after IRT testing, with explanations of their advantages and disadvantages 
• Selecting CFTR variant panels that enable equal detection of CF in all populations within the screening jurisdiction 
• Reporting results 
• Roles and responsibilities during STFU through diagnosis This guideline recommends the use of CFTR variant panels in CF NBS algorithms when resources allow. 

The intended users of this guideline are NBS laboratory, follow-up, and program personnel; public health program administrators; medical laboratories; CF center personnel and organizations responsible for CF center networks; health care providers (HCPs) (e.g., primary care providers, neonatologists, pediatricians); regulatory agencies; public health policy makers; and manufacturers of instruments, reagents, and related products used for NBS testing. 

Although the need for confirmatory diagnostic testing is discussed, this guideline describes only some of the issues regarding satisfactory sweat chloride testing. In addition, this guideline: 
• Is not intended to provide details of confirmatory diagnostic laboratory testing 
• Does not include comparative cost information 
• Does not cover CF prenatal carrier screening or prenatal diagnosis