HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Votava, F. Search for Related Content PubMed PubMed Citation Articles by Votava, F.

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

¹ Department of Paediatrics, Medical University of Vienna, Vienna, Austria, ² Department of Paediatrics, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic, ³ Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ⁴ 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary, ⁵ Department of Paediatrics, University of Szeged, Szeged, Hungary, ⁶ 2nd Department of Paediatrics, Comenius University, Bratislava, Slovakia and ⁷ University Children’s Hospital, University Medical Centre, Ljubljana, Slovenia

(Correspondence should be addressed to F Waldhauser, Department of Paediatrics, University of Vienna, AKH-Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Email: franz.waldhauser{at}meduniwien.ac.at)

Objective: Newborn screening based on measurement of 17-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/l) 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 33 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 of 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.

This article has been cited by other articles:

				J. E. Lee, Y. Moon, M. H. Lee, Y. H. Jun, K. I. Oh, and J. W. Choi Corrected 17-Alpha-Hydroxyprogesterone Values Adjusted by a Scoring System for Screening Congenital Adrenal Hyperplasia in Premature Infants Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 235 - 240. [Abstract] [Full Text] [PDF]

				C. Moran, R. Azziz, N. Weintrob, S. F. Witchel, V. Rohmer, D. Dewailly, J. A. M. Marcondes, M. Pugeat, P. W. Speiser, D. Pignatelli, et al. Reproductive Outcome of Women with 21-Hydroxylase-Deficient Nonclassic Adrenal Hyperplasia J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3451 - 3456. [Abstract] [Full Text] [PDF]