TY - JOUR
T1 - Second-tier testing for 21-hydroxylase deficiency in the Netherlands; a newborn screening pilot study
AU - Stroek, Kevin
AU - Ruiter, An
AU - van der Linde, Annelieke
AU - Ackermans, Mariette
AU - Bouva, Marelle J
AU - Engel, Henk
AU - Jakobs, Bernadette
AU - Kemper, Evelien A
AU - van den Akker, Erica L T
AU - van Albada, Mirjam E
AU - Bocca, Gianni
AU - Finken, Martijn J J
AU - Hannema, Sabine E
AU - Houdijk, E C A Mieke
AU - van der Kamp, Hetty J
AU - van Tellingen, Vera
AU - van Trotsenburg, A S Paul
AU - Zwaveling-Soonawala, Nitash
AU - Bosch, Annet M
AU - de Jonge, Robert
AU - Heijboer, Annemieke C
AU - Claahsen-van der Grinten, Hedi L
AU - Boelen, Anita
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2021/6/25
Y1 - 2021/6/25
N2 - BACKGROUND: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cut-off values. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false-positives. We assessed the accuracy and turnaround time of the current CAH NBS-algorithm and compared this to alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot-study.METHODS: Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019 21-DF concentrations were analyzed by liquid chromatography-tandem mass spectrometry, in parallel with routine NBS. Diagnoses were confirmed by mutation analysis.RESULTS: 328 DBS were analyzed. 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. In the second-tier, all 37 confirmed CAH had elevated 21-DF concentrations, all 33 false-positives and 253/258 second HP negatives had undetectable 21-DF concentrations. The elevated 21-DF of the other five newborns may be NBS false-negatives or second-tier false-positives. Adding the second-tier to inconclusive first HPs reduced the number of false-positives to 11 and prevented all 286 second HPs. Adding the second-tier to both positive and inconclusive first HPs eliminated all false-positives at the cost of delayed referral for 31 CAH patients (1-4 days).CONCLUSION: Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false-positives, abolishing the second HP and thereby shortening referral time.
AB - BACKGROUND: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cut-off values. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false-positives. We assessed the accuracy and turnaround time of the current CAH NBS-algorithm and compared this to alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot-study.METHODS: Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019 21-DF concentrations were analyzed by liquid chromatography-tandem mass spectrometry, in parallel with routine NBS. Diagnoses were confirmed by mutation analysis.RESULTS: 328 DBS were analyzed. 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. In the second-tier, all 37 confirmed CAH had elevated 21-DF concentrations, all 33 false-positives and 253/258 second HP negatives had undetectable 21-DF concentrations. The elevated 21-DF of the other five newborns may be NBS false-negatives or second-tier false-positives. Adding the second-tier to inconclusive first HPs reduced the number of false-positives to 11 and prevented all 286 second HPs. Adding the second-tier to both positive and inconclusive first HPs eliminated all false-positives at the cost of delayed referral for 31 CAH patients (1-4 days).CONCLUSION: Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false-positives, abolishing the second HP and thereby shortening referral time.
U2 - 10.1210/clinem/dgab464
DO - 10.1210/clinem/dgab464
M3 - Article
C2 - 34171085
SP - 1
EP - 24
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
ER -