{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:02Z","timestamp":1784557142709,"version":"3.55.0"},"reference-count":27,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["etj.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic\/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007\u20132017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model\u2019s performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The PPV improved significantly (26\u201348%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-23-0141","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T14:55:30Z","timestamp":1697036130000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-16","source":"Crossref","is-referenced-by-count":14,"title":["Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2359-2865","authenticated-orcid":true,"given":"Heleen I","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"van Haeringen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"},{"name":"Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marelle J","family":"Bouva","sequence":"additional","affiliation":[{"name":"Reference Laboratory Neonatal Screening, Center for Health protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy P J","family":"den Elzen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Specialized Diagnostics & Research, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"},{"name":"Amsterdam Public Health, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-8497","authenticated-orcid":true,"given":"Eveline","family":"Bruinstroop","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina P B","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"TNO - Child Health, Sylviusweg, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A S Paul","family":"van Trotsenburg","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Paediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitash","family":"Zwaveling-Soonawala","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Paediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-9955","authenticated-orcid":true,"given":"Annemieke C","family":"Heijboer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet M","family":"Bosch","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Pediatrics, Division of Metabolic Disorders, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Amsterdam UMC, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hoogendoorn","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-2918","authenticated-orcid":true,"given":"Anita","family":"Boelen","sequence":"additional","affiliation":[{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Orphanet Journal of Rare Diseases","first-page":"17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","unstructured":"Rastogi MV & LaFranchi SH. 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