Kids in America

Newborn Screening for Cystic Fibrosis

Laura M. Bender,PhD; Steven W. Cotten,PhD; Monte S. Willis,MD


Lab Med. 2011;42(10):595-601. 

In This Article

Abstract and Introduction


Within the last year, all 50 states in the United States have adopted newborn screening (NBS) protocols for cystic fibrosis (CF), the most common fatal autosomal recessive disease among Caucasian populations. In this overview, we discuss the rationale for implementing NBS for CF and discuss the different testing algorithms states have adopted. Based on studies in the United States, Australia, and the United Kingdom, these measures will likely lead to less severe disease, prolonged life, and more cost-effective management of CF in the long run.


The introduction of newborn screening (NBS) programs follows growing evidence of the benefits of identifying cystic fibrosis (CF) early.[1] Randomized clinical trials,[2–5] observational studies,[6–10] and data gathered from CF databases[11,12] all have identified the benefits of CF NBS. Early identification of CF by NBS allows improvements in nutritional, respiratory, gastrointestinal, and cognitive function.[13,14] It also allows genetic counseling for carrier parents and more widespread family testing.[15] But these benefits do not come without some adversity. In particular, the anxiety associated with false-positive diagnostic tests is 1 drawback to CF NBS. A CDC workshop addressed this issue and concluded that the health benefits outweighed the risk and harm to justify CF screening.[16] Similarly, a consensus conference organized by the European Cystic Fibrosis Society, the International Society for Neonatal Screening, the European Molecular Genetic Quality Network, and the EU EuroGentest Network of Excellence concluded that CF NBS would be supported by the evidence with respect to health benefits and clinical outcomes.[13]

Meta-analysis of randomized trials of CF NBS in Europe and Australia demonstrate a 5%–10% reduction in mortality by the age of 10 in children with CF without meconium ileus.[17] The detection of CF by screening resulted in better lung function, improved growth parameters, and less intensive therapy compared to children diagnosed with CF clinically in a number of observational studies.[7,10,18–22] Improvement in pulmonary function and overall outcomes have not been definitively confirmed by randomized trials,[23,3] but growth and nutritional outcome improvement through adolescence has been documented in randomized trials where children were identified by CF NBS and compared to those diagnosed based on symptoms.[2] An improvement in neurocognitive outcome in infants and young children has been identified when CF NBS is used and nutritional intervention is applied early.[2,21,24–26] An unintended benefit of CF NBS has been its cost effectiveness. A U.K. Cystic Fibrosis study compared the annual costs of long-term therapies and IV antibiotics for children whose CF was identified through a NBS program compared to children identified clinically after the age of 2 months.[27] The cost of therapy was lower in those identified by NBS.

Multiple diagnostic modalities have been developed since the identification of CF. In 1979, screening for elevated immunoreactive trypsinogen (IRT) in dried blood spots was published.[28] The use of IRT was implemented in Australia in 1981, where 2 consecutive IRT tests, taken at day 3–5 after birth and repeated 3–5 weeks later, was first used to screen newborns for CF.[29] In 1994, they added the direct DNA analysis of CF transmembrane conductance regulator (CFTR) as part of a national NBS screening program. In 1989, CFTR was identified as the gene mutated in CF and mapped to chromosome 7; there are currently more than 1800 cataloged mutations.[11,30] When the IRT followed by DNA was compared to the IRT/IRT (followed by DNA analysis), it was concluded that the false-positive rate was much lower for IRT/DNA analysis (0.69% vs 0.0543%), and this proved to be a more beneficial screening strategy for the population in question.[31] While standardized sweat testing to detect elevated sweat chloride levels in CF patients was implemented in 1959 to diagnose CF,[32] it has continued to play a prominent role in confirming the diagnosis of CF in many NBS algorithms. These 3 testing modalities—IRT, direct DNA analysis, and sweat chloride analysis—comprise the basis of NBS programs internationally.


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