TY - JOUR
T1 - Lessons learned from 5 years of newborn screening for congenital adrenal hyperplasia in the Czech Republic
T2 - 17-hydroxyprogesterone, genotypes, and screening performance
AU - Votava, Felix
AU - Novotna, Dana
AU - Kracmar, Petr
AU - Vinohradska, Hana
AU - Stahlova-Hrabincova, Eva
AU - Vrzalova, Zuzana
AU - Neumann, David
AU - Malikova, Jana
AU - Lebl, Jan
AU - Matern, Dietrich
N1 - Funding Information:
Acknowledgments The authors are very grateful to Dr A.M. Wallace, Department of Clinical Biochemistry, Glasgow, Scotland, and Mark McCann, Minnesota Department of Health, St. Paul, Minnesota, USA for 17OHP measurements in NBS samples. The study was supported by the Czech Ministry of Health, project IGA numbers 9981-3 and NT12213 and by the Czech Ministry of Education, project numbers MSM0021620814 and grant numbers MSMT LC06023.
PY - 2012/6
Y1 - 2012/6
N2 - 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 (n021); in severe/moderate, 321 nmol/L (n030); in moderate, 61 nmol/L (n020); and in mild genotypes, 31 nmol/L (n07). 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.
AB - 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 (n021); in severe/moderate, 321 nmol/L (n030); in moderate, 61 nmol/L (n020); and in mild genotypes, 31 nmol/L (n07). 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.
KW - 17-Hydroxyprogesterone
KW - CYP21 gene
KW - Congenital adrenal hyperplasia
KW - Newborn screening
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U2 - 10.1007/s00431-011-1656-6
DO - 10.1007/s00431-011-1656-6
M3 - Article
C2 - 22234478
AN - SCOPUS:84863726767
SN - 0943-9676
VL - 171
SP - 935
EP - 940
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
IS - 6
ER -