Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

Felix Votava, Dóra Török, József Kovács, Dorothea Möslinger, Sabina M. Baumgartner-Parzer, J. Sólyom, Zuzana Pribilincová, Tadej Battelino, Jan Lebl, Herwig Frisch, Franz Waldhauser, P. Blümel, M. Borkenstein, J. Fussenegger, Z. Jaros, K. Kapelari, P. Kurnik, R. Puttinger, K. Schmitt, O. HníkováB. Kalvachová, J. Klabochová, S. Koloušková, L. Lisá, V. Rakosniková, Š Průhová, R. Průša, J. Škvor, M. Šnajderová, J. Venháčová, J. Zapletalová, J. Zeman, E. Erhardt, Z. Halász, I. Ilyés, L. Ságodi, G. Soltész, E. Sólyom, L. Szabó, P. Szütz, S. Bieliková, M. Debreová, J. Javorková, L. Košt'álová, M. Kúseková, Ž Mišíková, J. Strnová, Z. Šimeková, D. Trezová, N. Bratanič, V. Dolžan, C. Križišnik, B. Repič-Lampret, M. Stopar, K. Trebušak, N. Uršič-Bratina, M. Žerjav-Tanšek

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: Newborn screening based on measurement of 17α-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis: in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. Methods: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. Results: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/1) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 3 3 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. Conclusion: Newborn screening is efficient for diagnosing the SW form CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.

Original languageEnglish
Pages (from-to)869-874
Number of pages6
JournalEuropean Journal of Endocrinology
Volume152
Issue number6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

Congenital Adrenal Hyperplasia
Newborn Infant
Salts
Puberty
Early Diagnosis
Fluoroimmunoassay
17-alpha-Hydroxyprogesterone
Androgens
Mutation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Votava, F., Török, D., Kovács, J., Möslinger, D., Baumgartner-Parzer, S. M., Sólyom, J., ... Žerjav-Tanšek, M. (2005). Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia. European Journal of Endocrinology, 152(6), 869-874. https://doi.org/10.1530/eje.1.01929

Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia. / Votava, Felix; Török, Dóra; Kovács, József; Möslinger, Dorothea; Baumgartner-Parzer, Sabina M.; Sólyom, J.; Pribilincová, Zuzana; Battelino, Tadej; Lebl, Jan; Frisch, Herwig; Waldhauser, Franz; Blümel, P.; Borkenstein, M.; Fussenegger, J.; Jaros, Z.; Kapelari, K.; Kurnik, P.; Puttinger, R.; Schmitt, K.; Hníková, O.; Kalvachová, B.; Klabochová, J.; Koloušková, S.; Lisá, L.; Rakosniková, V.; Průhová, Š; Průša, R.; Škvor, J.; Šnajderová, M.; Venháčová, J.; Zapletalová, J.; Zeman, J.; Erhardt, E.; Halász, Z.; Ilyés, I.; Ságodi, L.; Soltész, G.; Sólyom, E.; Szabó, L.; Szütz, P.; Bieliková, S.; Debreová, M.; Javorková, J.; Košt'álová, L.; Kúseková, M.; Mišíková, Ž; Strnová, J.; Šimeková, Z.; Trezová, D.; Bratanič, N.; Dolžan, V.; Križišnik, C.; Repič-Lampret, B.; Stopar, M.; Trebušak, K.; Uršič-Bratina, N.; Žerjav-Tanšek, M.

In: European Journal of Endocrinology, Vol. 152, No. 6, 06.2005, p. 869-874.

Research output: Contribution to journalArticle

Votava, F, Török, D, Kovács, J, Möslinger, D, Baumgartner-Parzer, SM, Sólyom, J, Pribilincová, Z, Battelino, T, Lebl, J, Frisch, H, Waldhauser, F, Blümel, P, Borkenstein, M, Fussenegger, J, Jaros, Z, Kapelari, K, Kurnik, P, Puttinger, R, Schmitt, K, Hníková, O, Kalvachová, B, Klabochová, J, Koloušková, S, Lisá, L, Rakosniková, V, Průhová, Š, Průša, R, Škvor, J, Šnajderová, M, Venháčová, J, Zapletalová, J, Zeman, J, Erhardt, E, Halász, Z, Ilyés, I, Ságodi, L, Soltész, G, Sólyom, E, Szabó, L, Szütz, P, Bieliková, S, Debreová, M, Javorková, J, Košt'álová, L, Kúseková, M, Mišíková, Ž, Strnová, J, Šimeková, Z, Trezová, D, Bratanič, N, Dolžan, V, Križišnik, C, Repič-Lampret, B, Stopar, M, Trebušak, K, Uršič-Bratina, N & Žerjav-Tanšek, M 2005, 'Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia', European Journal of Endocrinology, vol. 152, no. 6, pp. 869-874. https://doi.org/10.1530/eje.1.01929
Votava, Felix ; Török, Dóra ; Kovács, József ; Möslinger, Dorothea ; Baumgartner-Parzer, Sabina M. ; Sólyom, J. ; Pribilincová, Zuzana ; Battelino, Tadej ; Lebl, Jan ; Frisch, Herwig ; Waldhauser, Franz ; Blümel, P. ; Borkenstein, M. ; Fussenegger, J. ; Jaros, Z. ; Kapelari, K. ; Kurnik, P. ; Puttinger, R. ; Schmitt, K. ; Hníková, O. ; Kalvachová, B. ; Klabochová, J. ; Koloušková, S. ; Lisá, L. ; Rakosniková, V. ; Průhová, Š ; Průša, R. ; Škvor, J. ; Šnajderová, M. ; Venháčová, J. ; Zapletalová, J. ; Zeman, J. ; Erhardt, E. ; Halász, Z. ; Ilyés, I. ; Ságodi, L. ; Soltész, G. ; Sólyom, E. ; Szabó, L. ; Szütz, P. ; Bieliková, S. ; Debreová, M. ; Javorková, J. ; Košt'álová, L. ; Kúseková, M. ; Mišíková, Ž ; Strnová, J. ; Šimeková, Z. ; Trezová, D. ; Bratanič, N. ; Dolžan, V. ; Križišnik, C. ; Repič-Lampret, B. ; Stopar, M. ; Trebušak, K. ; Uršič-Bratina, N. ; Žerjav-Tanšek, M. / Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia. In: European Journal of Endocrinology. 2005 ; Vol. 152, No. 6. pp. 869-874.
@article{9a6d88ea55fd4481a354d175be6dc4a5,
title = "Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia",
abstract = "Objective: Newborn screening based on measurement of 17α-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis: in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. Methods: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. Results: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/1) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 3 3 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. Conclusion: Newborn screening is efficient for diagnosing the SW form CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.",
author = "Felix Votava and D{\'o}ra T{\"o}r{\"o}k and J{\'o}zsef Kov{\'a}cs and Dorothea M{\"o}slinger and Baumgartner-Parzer, {Sabina M.} and J. S{\'o}lyom and Zuzana Pribilincov{\'a} and Tadej Battelino and Jan Lebl and Herwig Frisch and Franz Waldhauser and P. Bl{\"u}mel and M. Borkenstein and J. Fussenegger and Z. Jaros and K. Kapelari and P. Kurnik and R. Puttinger and K. Schmitt and O. Hn{\'i}kov{\'a} and B. Kalvachov{\'a} and J. Klabochov{\'a} and S. Kolouškov{\'a} and L. Lis{\'a} and V. Rakosnikov{\'a} and Š Průhov{\'a} and R. Průša and J. Škvor and M. Šnajderov{\'a} and J. Venh{\'a}čov{\'a} and J. Zapletalov{\'a} and J. Zeman and E. Erhardt and Z. Hal{\'a}sz and I. Ily{\'e}s and L. S{\'a}godi and G. Solt{\'e}sz and E. S{\'o}lyom and L. Szab{\'o} and P. Sz{\"u}tz and S. Bielikov{\'a} and M. Debreov{\'a} and J. Javorkov{\'a} and L. Košt'{\'a}lov{\'a} and M. K{\'u}sekov{\'a} and Ž Miš{\'i}kov{\'a} and J. Strnov{\'a} and Z. Šimekov{\'a} and D. Trezov{\'a} and N. Bratanič and V. Dolžan and C. Križišnik and B. Repič-Lampret and M. Stopar and K. Trebušak and N. Uršič-Bratina and M. Žerjav-Tanšek",
year = "2005",
month = "6",
doi = "10.1530/eje.1.01929",
language = "English",
volume = "152",
pages = "869--874",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "6",

}

TY - JOUR

T1 - Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

AU - Votava, Felix

AU - Török, Dóra

AU - Kovács, József

AU - Möslinger, Dorothea

AU - Baumgartner-Parzer, Sabina M.

AU - Sólyom, J.

AU - Pribilincová, Zuzana

AU - Battelino, Tadej

AU - Lebl, Jan

AU - Frisch, Herwig

AU - Waldhauser, Franz

AU - Blümel, P.

AU - Borkenstein, M.

AU - Fussenegger, J.

AU - Jaros, Z.

AU - Kapelari, K.

AU - Kurnik, P.

AU - Puttinger, R.

AU - Schmitt, K.

AU - Hníková, O.

AU - Kalvachová, B.

AU - Klabochová, J.

AU - Koloušková, S.

AU - Lisá, L.

AU - Rakosniková, V.

AU - Průhová, Š

AU - Průša, R.

AU - Škvor, J.

AU - Šnajderová, M.

AU - Venháčová, J.

AU - Zapletalová, J.

AU - Zeman, J.

AU - Erhardt, E.

AU - Halász, Z.

AU - Ilyés, I.

AU - Ságodi, L.

AU - Soltész, G.

AU - Sólyom, E.

AU - Szabó, L.

AU - Szütz, P.

AU - Bieliková, S.

AU - Debreová, M.

AU - Javorková, J.

AU - Košt'álová, L.

AU - Kúseková, M.

AU - Mišíková, Ž

AU - Strnová, J.

AU - Šimeková, Z.

AU - Trezová, D.

AU - Bratanič, N.

AU - Dolžan, V.

AU - Križišnik, C.

AU - Repič-Lampret, B.

AU - Stopar, M.

AU - Trebušak, K.

AU - Uršič-Bratina, N.

AU - Žerjav-Tanšek, M.

PY - 2005/6

Y1 - 2005/6

N2 - Objective: Newborn screening based on measurement of 17α-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis: in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. Methods: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. Results: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/1) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 3 3 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. Conclusion: Newborn screening is efficient for diagnosing the SW form CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.

AB - Objective: Newborn screening based on measurement of 17α-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis: in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. Methods: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. Results: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/1) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 3 3 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. Conclusion: Newborn screening is efficient for diagnosing the SW form CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.

UR - http://www.scopus.com/inward/record.url?scp=21344441963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21344441963&partnerID=8YFLogxK

U2 - 10.1530/eje.1.01929

DO - 10.1530/eje.1.01929

M3 - Article

C2 - 15941926

AN - SCOPUS:21344441963

VL - 152

SP - 869

EP - 874

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 6

ER -