{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:10:53Z","timestamp":1790619053276,"version":"4.1.0"},"reference-count":20,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age\u2013adjusted cutoffs. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false positives.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab464","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T16:45:58Z","timestamp":1624639558000},"page":"e4487-e4496","source":"Crossref","is-referenced-by-count":30,"title":["Second-tier Testing for 21-Hydroxylase Deficiency in the Netherlands: A Newborn Screening Pilot Study"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3838-4583","authenticated-orcid":false,"given":"Kevin","family":"Stroek","sequence":"first","affiliation":[{"name":"Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Ruiter","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelieke","family":"van der Linde","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Radboud University Nijmegen Medical Centre, 6525GA Nijmegen, The Netherlands"},{"name":"Department of Pediatrics, Amphia Hospital, 4818CK Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2722-2653","authenticated-orcid":false,"given":"Mariette","family":"Ackermans","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marelle J","family":"Bouva","sequence":"additional","affiliation":[{"name":"Center for Health protection, National Institute for Public Health and the Environment, 3721MA Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-6720","authenticated-orcid":false,"given":"Henk","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Isala Hospital, 8025AB Zwolle, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Jakobs","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Elisabeth-Tweesteden Hospital, 5022GC Tilburg, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien A","family":"Kemper","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, IJsselland Hospital, 2906ZC Capelle aan den IJssel, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-9328","authenticated-orcid":false,"given":"Erica L T","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sophia Children\u2019s Hospital, Erasmus University Medical Center, 3015CN Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5282-3365","authenticated-orcid":false,"given":"Mirjam E","family":"van Albada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beatrix Children\u2019s Hospital, University Medical Center Groningen, 9713GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2665-8738","authenticated-orcid":false,"given":"Gianni","family":"Bocca","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beatrix Children\u2019s Hospital, University Medical Center Groningen, 9713GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-9788","authenticated-orcid":false,"given":"Martijn J J","family":"Finken","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-0993","authenticated-orcid":false,"given":"Sabine E","family":"Hannema","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E C A","family":"Mieke Houdijk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juliana Children\u2019s Hospital, 2545AA the Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty J","family":"van der Kamp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, 3584EA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"van Tellingen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Catharina Hospital, 5623EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-7441","authenticated-orcid":false,"given":"A S","family":"Paul van Trotsenburg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-5541","authenticated-orcid":false,"given":"Nitash","family":"Zwaveling-Soonawala","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5027-5916","authenticated-orcid":false,"given":"Annet M","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Metabolic Disorders, Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-0094","authenticated-orcid":false,"given":"Robert","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit & University of Amsterdam, 1105AZ Amsterdam, The 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