Additional sensitivity data for newborn screening for congenital adrenal hyperplasia in Wisconsin.
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Adrenal Hyperplasia, Congenital↗
Biomedical subjects
Gary L Hoffman
Publications and source records attributed to Gary L Hoffman.
Newborn screening for congenital adrenal hyperplasia has reduced sensitivity in girls.
OBJECTIVES: To characterize Wisconsin-born infants with 21-hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH) who were not identified by the newborn screening for 21-OH-D-CAH, and to examine male and female screening 17-hydroxyprogesterone (17-OHP) levels. STUDY DESIGN: Information on infants with false-negative results was gathered. Results of the Wisconsin newborn screening for 21-OH-D-CAH from January 1, 2000, to June 30, 2003, were analyzed to detect possible differences between male (n=119,842) and female (n=114,951) infants. RESULTS: Six of 7 female infants with false-negative results had genital masculinization, and 4 of 8 infants with false-negative results had laboratory evidence of salt-wasting. None died, had a salt-wasting crisis, or was assigned the wrong sex. A significant difference in the mean 17-OHP levels between male (17.5 ng/mL) and female (15.4 ng/mL) infants (P <.0001) was detected. The sensitivity of newborn screening for female infants was 60%, compared with 80% for male infants. CONCLUSIONS: Male and female infants have significantly different mean 17-OHP levels on newborn screening, and female infants comprise most of the infants with false-negative results. Although health professionals should not assume that newborn screening for 21-OH-D-CAH is a means of identifying all affected infants, the primary goals of newborn screening for CAH (prevention of salt-wasting crises and sex misassignment) are fulfilled.
17-alpha-Hydroxyprogesterone↗
Multiplexed genetic analysis using an expanded genetic alphabet.
BACKGROUND: All states require some kind of testing for newborns, but the policies are far from standardized. In some states, newborn screening may include genetic tests for a wide range of targets, but the costs and complexities of the newer genetic tests inhibit expansion of newborn screening. We describe the development and technical evaluation of a multiplex platform that may foster increased newborn genetic screening. METHODS: MultiCode PLx involves three major steps: PCR, target-specific extension, and liquid chip decoding. Each step is performed in the same reaction vessel, and the test is completed in approximately 3 h. For site-specific labeling and room-temperature decoding, we use an additional base pair constructed from isoguanosine and isocytidine. We used the method to test for mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The developed test was performed manually and by automated liquid handling. Initially, 225 samples with a range of genotypes were tested retrospectively with the method. A prospective study used samples from >400 newborns. RESULTS: In the retrospective study, 99.1% of samples were correctly genotyped with no incorrect calls made. In the perspective study, 95% of the samples were correctly genotyped for all targets, and there were no incorrect calls. CONCLUSIONS: The unique genetic multiplexing platform was successfully able to test for 31 targets within the CFTR gene and provides accurate genotype assignments in a clinical setting.
Autoanalysis↗
Screening newborns for congenital disorders.
The Newborn Screening Laboratory at the Wisconsin State Laboratory of Hygiene (WSLH) tests all newborn babies in the state of Wisconsin for 26 congenital disorders. The screening is mandated by state statute (253.13) and attempts to identify those babies at highest risk for any of the screened-for congenital disorders. The Newborn Screening Laboratory at the WSLH is part of the state's newborn screening program, a cooperative effort between the Wisconsin Department of Health and Family Services, state birthing hospital staff, several public and private specialty clinics, primary care providers, and parents. Screening occurs within the first hours (median 38 hours) of life when a few drops of blood from the baby's heel is collected, applied to a special paper, dried, and sent to the WSLH for analysis. Those babies determined to have at-risk test results get repeat testing to confirm the initial test results and, if warranted, the baby is referred to a specialty clinic for a diagnostic work-up and treatment if necessary. Since its inception in the early 1960s, newborn screening in Wisconsin has saved approximately 1300 children from serious mental or other medical problems.
Congenital Abnormalities↗
Newborn screening with tandem mass spectrometry: examining its cost-effectiveness in the Wisconsin Newborn Screening Panel.
OBJECTIVE: To examine the cost-effectiveness of tandem mass spectrometry (MS/MS) in a neonatal screening panel for 14 fatty acid oxidation and organic acidemia disorders in the Wisconsin Newborn Screening Program. STUDY DESIGN: An incremental cost-effectiveness analysis with a hypothetical cohort of 100,000 infants was performed. A threshold of $50,000/QALY (quality-adjusted life-year) was used to determine whether screening for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) alone is cost-effective or whether additional disorders would need to be incorporated into the analysis to arrive at a conclusion regarding the overall cost-effectiveness of MS/MS. RESULTS: Under conservative assumptions, screening for MCAD alone yields an incremental cost-effectiveness ratio of $41,862/QALY. With the use of more realistic assumptions, screening becomes more cost-effective ($6008/QALY) and remains cost-effective so long as the incremental cost of screening remains under $13.05 per test. Adding the incremental costs of detecting the 13 other disorders on the screening panel still yields a result well within accepted norms for cost-effectiveness ($15,252/QALY). CONCLUSIONS: In Wisconsin, MS/MS screening for MCAD alone appears to be cost-effective. Future analyses should examine the cost-effectiveness of alternative follow-up and treatment regimens for MCAD and other panel disorders.
Acyl-CoA Dehydrogenase↗