TY - JOUR
T1 - Second-tier Testing for 21-Hydroxylase Deficiency in the Netherlands
T2 - 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 - Mieke Houdijk, E. C. A.
AU - van der Kamp, Hetty J.
AU - van Tellingen, Vera
AU - Paul van Trotsenburg, A. S.
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 - Funding Information: This study was partially funded by Innovatiefonds Zorgverzekeraars (grant 3.412) and the Noyons prize of the Netherlands Society for Clinical Chemistry and Laboratory Medicine. Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Context: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cutoffs. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false positives. Objective: We assessed the accuracy and turnaround time of the current CAH NBS algorithm in comparison with 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 LC-MS/MS in parallel with routine NBS. Diagnoses were confirmed by mutation analysis. Results: A total of 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. With second-tier testing, all 37 confirmed CAH had elevated 21-DF, while all 33 false positives and 253/258 second-HP negatives had undetectable 21-DF. The elevated 21-DF of the other 5 newborns may be NBS false negatives or second-tier false positives. Adding the second-tier results 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 but 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 - Context: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cutoffs. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false positives. Objective: We assessed the accuracy and turnaround time of the current CAH NBS algorithm in comparison with 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 LC-MS/MS in parallel with routine NBS. Diagnoses were confirmed by mutation analysis. Results: A total of 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. With second-tier testing, all 37 confirmed CAH had elevated 21-DF, while all 33 false positives and 253/258 second-HP negatives had undetectable 21-DF. The elevated 21-DF of the other 5 newborns may be NBS false negatives or second-tier false positives. Adding the second-tier results 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 but 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.
KW - 21deoxycortisol
KW - CAH
KW - neonatal screening
KW - second tier
UR - http://www.scopus.com/inward/record.url?scp=85119486644&partnerID=8YFLogxK
U2 - https://doi.org/10.1210/clinem/dgab464
DO - https://doi.org/10.1210/clinem/dgab464
M3 - Article
C2 - 34171085
SN - 0021-972X
VL - 106
SP - E4487-E4496
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 11
ER -