de Hora, MarkHeather, NatashaWebster, DianneAlbert, BenjaminHofman, Paul2025-04-022025-04-022023-01(2023). Frontiers in Endocrinology, 14, 1226284.1664-2392https://hdl.handle.net/2292/71727Newborn screening for congenital adrenal hyperplasia using 17-hydroxyprogesterone by immunoassay remains controversial despite screening been available for almost 40 years. Screening is confounded by poor immunoassay specificity, fetal adrenal physiology, stress, and illness which can result in a large number of false positive screening tests. Screening programmes apply higher screening thresholds based on co-variates such as birthweight or gestational age but the false positive rate using immunoassay remains high. Mass spectrometry was first applied to newborn screening for congenital adrenal hyperplasia over 15 years ago. Elevated 17-hydroxprogesterone by immunoassay can be retested with a specific liquid chromatography tandem mass spectrometry assay that may include additional steroid markers. Laboratories register with quality assurance programme providers to ensure accurate steroid measurements. This has led to improvements in screening but there are additional costs and added laboratory workload. The search for novel steroid markers may inform further improvements to screening. Studies have shown that 11-oxygenated androgens are elevated in untreated patients and that the adrenal steroidogenesis backdoor pathway is more active in babies with congenital adrenal hyperplasia. There is continual interest in 21-deoxycortisol, a specific marker of 21-hydroxylase deficiency. The measurement of androgenic steroids and their precursors by liquid chromatography tandem mass spectrometry in bloodspots may inform improvements for screening, diagnosis, and treatment monitoring. In this review, we describe how liquid chromatography tandem mass spectrometry has improved newborn screening for congenital adrenal hyperplasia and explore how future developments may inform further improvements to screening and diagnosis.Electronic-eCollectionItems in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmHumansAdrenal Hyperplasia, CongenitalSteroidsNeonatal ScreeningChromatography, LiquidInfant, NewbornTandem Mass SpectrometryLCMSMSLCMSMS congenital adrenal hyperplasiabloodspotscongenital adrenal hyperplasianewborn screeningsteroid profiling3213 Paediatrics32 Biomedical and Clinical SciencesPreterm, Low Birth Weight and Health of the NewbornHealth ServicesRare DiseasesSexual and Gender Minorities (SGM/LGBT*)PediatricPerinatal Period - Conditions Originating in Perinatal PeriodClinical ResearchPrevention4.2 Evaluation of markers and technologiesMetabolic and endocrineScience & TechnologyLife Sciences & BiomedicineEndocrinology & Metabolism21-HYDROXYLASE DEFICIENCYBACKDOOR PATHWAYBIOLOGICAL SAMPLESSTEROID PROFILE17-ALPHA-HYDROXYPROGESTERONEMS/MSQUANTIFICATIONDERIVATIZATIONMETABOLISMTIER1103 Clinical Sciences1111 Nutrition and Dietetics3202 Clinical sciencesJournal Article10.3389/fendo.2023.1226284Copyright: The authors37850096 (pubmed)1664-2392Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/