Question

• Does newborn screening for CF improve morbidity, mortality, or quality of life?

Clinical Bottom Lines

1. Cystic fibrosis is an important health problem that occurs frequently enough to justify screening an entire population. Cystic fibrosis (CF) is a chronic, progressive, and life-shortening disease, which affects the pulmonary, gastrointestinal, reproductive, and other systems. The incidence of CF is 1 in 1,700 to 1 in 6,500 in the general population in the US.¹
2. Over 50% of patients with CF are diagnosed beyond one year of age.² The average life expectancy of patients with CF today is 32 years.
3. There is some evidence to suggest that treatment for cystic fibrosis is effective when initiaited early.^3,4
4. However, there is still overall insufficient data to support newborn screening:
   • While the diagnostic test is simple, safe, precise, and validated, there is insufficient cost-effectiveness data.

Summary of Key Evidence

1. A Cochrane review of studies regarding newborn screening for CF excluded all studies except for the Wisconsin trial, a randomized, controlled trial comparing newborn screening for CF and early treatment with later diagnosis and treatment.³
2. In the Wisconsin trial, 650,3341 neonates were screened for CF. Of these neonates, half were kept blinded from the families and investigators, and the other half were unblinded.⁴
3. The screening test was an ELISA for immunoreactive trypsin (IRT) performed on a dried blood spot, sensitivity 90-95%. If positive then a sweat test was done for confirmation. If the IRT was borderline positive, then a DNA analysis for the F508 mutation was performed, and if at least one allele was present then a sweat test was done.
4. 74 patients in the screened group were diagnosed with CF, vs. 75 in the control group. 3 false-negative IRT results occurred in the screened group, but the number of false-positive results was not reported. 18 false-positive results occurred in the control population, and the number of false-negative results was not reported.
5. Most outcome measures sought by the Cochrane group were not reported for the Wisconsin trial. Included in these outcome measures is number of respiratory infections requiring antibiotics, hospital admissions, occurrence of diabetes mellitus or liver cirrhosis, age at death, or sufficient cost-effectiveness data.
6. The nutritional data that was reported revealed that the proportion of patients with weight and height < 5% by 11 years was significantly less among the screened group. These data support newborn screening for CF.

Additional Comments

Citation

1. American Academy of Pediatrics, Newborn Screening Task Force. Serving the Family From Birth to the Medical Home. A Report From the Newborn Screening Task Force Convened in Washington DC, May 10-11, 1999. Pediatrics 2000; 106:386-427. 
2. American Academy of Pediatrics, Committee on Genetics. Newborn Screening Fact Sheets. Pediatrics 1996; 98:473-501.
3. Merelle ME, Lees CM, Nagelkerke AF, Dezateux C. Newborn screening for cystic fibrosis (Cochrane Review). In: The Cochrane Library, Issue 3, 2000. Oxford.
4. Farrell PM, Kosorok MR, Laxova A, et al. Nutritional benefits of neonatal screening for
   cystic fibrosis. N Engl J Med 1997; 337: 963-9

CAT Author: Susan Frangiskakis, MD

CAT Appraisers: Katherine Layton , MD

Date appraised: December 18, 2000