title: Lessons learned from 5 years of newborn screening for congenital adrenal hyperplasia in the Czech Republic: 17-hydroxyprogesterone, genotypes, and screening performance.
abstract: The aims were to summarize the experience and to determine the performance metrics of newborn screening (NBS) for congenital adrenal hyperplasia (CAH) in the Czech Republic. 17-Hydroxyprogesterone (17OHP) was measured in NBS samples prospectively in 545,026 newborns and retrospectively in 31 CAH patients born outside the study period. A total of 2,811 screened newborns had abnormal 17OHP; CAH was confirmed in 46 probands. One patient with a severe-moderate genotype of CAH had 17OHP below the cut-off and was diagnosed clinically. This corresponds to a screening sensitivity of 98% and a false positive rate (FPR) of 0.51%. The median of 17OHP in the most severe genotypes was 484 nmol/L (n = 21); in severe/moderate, 321 nmol/L (n = 30); in moderate, 61 nmol/L (n = 20); and in mild genotypes, 31 nmol/L (n = 7). NBS is efficient to detect severe CAH but may fail to detect milder variants. However, the FPR is too high but could be improved by application of a second tier test.
authors.affiliation: 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady, Department of Pediatrics, Charles University in Prague, Srobarova 50, 100 34, Prague 10, Czech Republic. votava@fnkv.cz
authors.forename: Felix
authors.initials: F
authors.lastname: Votava
authors.forename: Dana
authors.initials: D
authors.lastname: Novotna
authors.forename: Petr
authors.initials: P
authors.lastname: Kracmar
authors.forename: Hana
authors.initials: H
authors.lastname: Vinohradska
authors.forename: Eva
authors.initials: E
authors.lastname: Stahlova-Hrabincova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vrzalova
authors.forename: David
authors.initials: D
authors.lastname: Neumann
authors.forename: Jana
authors.initials: J
authors.lastname: Malikova
authors.forename: Jan
authors.initials: J
authors.lastname: Lebl
authors.forename: Dietrich
authors.initials: D
authors.lastname: Matern
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D018153:Czech Republic; D005189:False Positive Reactions; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013255:Steroid 21-Hydroxylase / Q000235:genetics
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D019326:17-alpha-Hydroxyprogesterone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase