{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:52:32Z","timestamp":1791337952268,"version":"4.3.1"},"reference-count":32,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000912","name":"March of Dimes","doi-asserted-by":"publisher","award":["6-FY14-440"],"award-info":[{"award-number":["6-FY14-440"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Single-tier newborn screening (NBS) for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24 to 48\u2005hours produces a high false-positive rate (FPR). Second-tier steroid testing can reduce the FPR and has been widely implemented.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We investigated the accuracy of an alternative multitier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the first-tier 17OHP cutoff to minimize missed cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We create a Minnesota-specific CYP21A2 pathogenic variants panel; developed a rapid, high-throughput multiplex, allele-specific-primer-extension assay; and performed a 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based 2-tier protocol and a molecular-based multitier NBS protocol, applied post hoc.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. The Centers for Disease Control and Prevention created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68 659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A 3-tier protocol with a lower first-tier steroid cutoff, second-tier 21-variant CYP21A2 panel, and third-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs, and 3 TPs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae297","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T19:00:56Z","timestamp":1714762856000},"page":"e1194-e1203","source":"Crossref","is-referenced-by-count":7,"title":["Can Incorporating Molecular Testing Improve the Accuracy of Newborn Screening for Congenital Adrenal Hyperplasia?"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-3629","authenticated-orcid":false,"given":"Kyriakie","family":"Sarafoglou","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School , Minneapolis, MN 55454 ,","place":["USA"]},{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy , Minneapolis, MN 55455 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Gaviglio","sequence":"additional","affiliation":[{"name":"Newborn Screening Program, Minnesota Department of Health , St. Paul, MN 55155 ,","place":["USA"]},{"name":"4ES Corporation , San Antonio, TX 78261 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Wolf","sequence":"additional","affiliation":[{"name":"Newborn Screening Program, Minnesota Department of Health , St. Paul, MN 55155 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