"We wanted to determine whether testing for SCID should be added to the universal screening panel for genetic disorders," said Dr. Sean McGhee, clinical instructor of pediatric immunology at Mattel Children's Hospital at UCLA. "Treatment is now advanced enough that 95 percent of children can be cured, but newborns must be detected in the first month, before the onset of severe infections."
In the first study -- detailed in the November edition of the Journal of Pediatrics -- UCLA researchers concluded that SCID screening could result in a large benefit to infants, making screening relatively cost-effective in spite of the low incidence of the disease. However, an adequate test would be critical to cost-effectiveness.
The analysis is the first of its kind to examine formally cost and benefits of SCID newborn screening.
To conduct the study, researchers used information about the costs of diagnosing and treating SCID and the benefits of early diagnosis, and performed a cost-benefit analysis comparing universal screening with screening only those with a family history of SCID.
Researchers determined that a SCID screening test that cost less than five dollars with a false-negative rate of 0.9 percent and a false-positive rate of 0.4 percent would be considered cost-effective by most currently accepted standards.
A nationwide screening program would cost an additional $23.9 million per year for screening costs, but would result in 760 years of life saved per year of screening.
In a related pilot study -- described in the December edition of Molecular Genetics and Metabolism -- McGhee and his colleagues looked at using a "two-tiered" strategy to improve the accuracy of SCID screenings.
"Existing tests for SCID are pretty good by themselves, but they do not provide sufficient accuracy in diagnosing the disorder to make them cost-effective," McGhee said. "We wanted to see if combining the two tests would limit the false positive results."
The current basis for the screening test is measurement of the number of lymphocytes at the time of birth that are normally very high, but very low in SCID infants. The screening is done by using dried blood samples obtained for other newborn screenings.
In the retrospective analysis, investigators measured serum or plasma levels of interleukin-7 (IL-7), a T-cell growth cytokine elevated in SCID, in combination with the previously developed T-cell receptor recombination excision circles assay.
They found that combining the tests in a two-tiered strategy decreased the false positive rate to nearly zero, which would be sufficient to allow cost-effective screening.
McGhee added that this strategy should be addressed in a multi-center, prospective trial to determine accurately the incidence, specificity, sensitivity and cost of SCID newborn screening.
The incidence of SCID is unknown but may be more common than published estimates because infants frequently die of infection before diagnosis. If an infant is diagnosed -- preferably within the first month of life -- and before their first infection, most can be treated with a bone-marrow transplant. About half of the patients can be cured; the other half may require intravenous immune globulin therapy treatments, but can live normal lives.
Other UCLA authors on both studies included Dr. E. Richard Stiehm and Dr. Edward McCabe. In addition, Dr. Morton Cowan, University of California, San Francisco, and Dr. Paul Krogstad, UCLA, co-authored the study on the two-tiered universal newborn screening strategy.
Support for all research was provided by the human and molecular development training grant at the David Geffen School of Medicine at UCLA, NIH/NICHD and the Culpepper Biomedical Pilot Initiative of the John D. Rockefeller Foundation.
McCabe is an adviser to GeneFluidics, a nanotechnology company involved in genetic testing.