Newborn screening for cystic fibrosis.

To the Editor: Newborn screening is a well-established approach for identifying genetic diseases with a 40-year history of improving public health. (1) The debate about justification for screening newborns for cystic fibrosis (CF) continues; however, the Centers for Disease Control and Prevention (CDC) recommends that individual states consider planning and implementing newborn screening for CF with consideration for the magnitude of benefits, cost, and the need to minimize risks. (2) Clinical benefits for CF newborn screening are early nutritional intervention that improves growth and cognitive development with other benefits ranging from reduced hospitalizations to improved survival. (2) There is unclear evidence that pulmonary outcomes are improved by newborn screening with potential harm being psychosocial risks for carrier children and exposure of young children to infectious agents through patient interactions in clinical settings. (2) Presently, there is no uniformity in the eight states that have mandatory CF newborn screening programs, which includes three southern states, Mississippi, Oklahoma, and South Carolina.

The first CF newborn screening program began in Colorado in 1983 followed by Wisconsin in 1985. Lee and colleagues reported that CF newborn screening was a potential cost-saving alternative to the traditional method of diagnosing CF with a reduction in sweat chloride tests from 1,670 to 804 annual tests. (3) The estimated annual cost of the Wisconsin CF newborn screening and diagnosis was $4.58 per newborn infant and the estimated annual cost per newly diagnosed CF infant using the traditional method was $4.97 per newborn infant. (3)

The current methodology for CF newborn screening by the Wisconsin Newborn Screening Laboratory is a two-tier process with the initial step being the measurement of immunoreactive trypsinogen (IRT) levels of the dried blood spot on Guthrie cards from newborn infants with abnormal IRT levels defined as [greater than or equal to] 170 ng/mL followed by the second step being a 25 genetic mutation analysis on the highest 4% of the daily IRT levels. Positive newborn screens are confirmed by sweat chloride testing by pilocarpine iontophoresis. The other newborn screening program commonly utilized is repeating the IRT level as the second tier. The Wisconsin group showed that the two-tier newborn screen with IRT testing followed by DNA mutation analysis decreased the number of false-positives without a significant increase in cost. (4)

The survival rate for patients with CF has dramatically improved over the past fifty years due to scientific advancement. Further innovation includes newborn screening which leads to a diagnosis of CF one year earlier on average than symptomatic detection. CF newborn screening significantly reduces morbidity and mortality, in addition to being cost-effective, with reduced expenses for workup of failure to thrive, reduced number of unnecessary sweat tests, reduced hospitalizations, and improved survival rates. States presently not performing CF newborn screening should consider adopting such a program and should strongly consider the two-tier process with IRT level testing followed by genetic mutation analysis with its proven efficacy and efficiency in Wisconsin. Standardized CF newborn screen testing is needed and should be a consideration for future recommendations by the CDC.

Don Hayes, Jr., MD

Adult and Pediatric Pulmonary Fellow

Departments of Medicine and Pediatrics

University of Wisconsin School of Medical and Public Health

Madison, WI

References

1. McCabe LL, Therell BL Jr, McCabe ER. Newborn screening: rationale for a comprehensive, fully integrated public health system. Mol Genet Metab 2002;77:267-273.

2. Grosse SD, Boyle CA, Botkin JR, et al. Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 2004;53:1-36.

3. Lee DS, Rosenberg MA, Peterson A, et al. Analysis of the costs of diagnosing cystic fibrosis with a newborn screening program. J Pediatr 2003;142:617-623.

4. Gregg RG, Wilfond BS, Farrell PM, et al. Application of DNA analysis in a population screening program for neonatal diagnosis of cystic fibrosis (CF): comparison of screening protocols. Am J Hum Genet 1993;52:616-626.

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