{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:25:13Z","timestamp":1790814313371,"version":"4.1.0"},"reference-count":59,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":389,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroid hormone (TH) is essential for brain development in utero and during the first 2 to 3 years of life. The negative effects of TH deficiency on brain development are irreversible. Early detection of TH deficiency in neonates (congenital hypothyroidism (CH) through newborn screening (NBS)) allows for early treatment, thereby preventing brain damage. Screening for CH began in 1973 with the measurement of total thyroxine (T4) in dried blood spots. The enhanced sensitivity of thyroid-stimulating hormone (TSH) measurement has prompted a shift in the approach to NBS for CH. Currently, worldwide, the majority of NBS programs for CH employ TSH as the primary screening marker. However, a select few programs still utilize T4 as the primary marker, enabling the detection of both primary and central CH. This review provides an overview of the laboratory aspects of the screening on CH from the start of screening to the present.<\/jats:p>","DOI":"10.1530\/etj-24-0325","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T08:27:19Z","timestamp":1737707239000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":6,"title":["Newborn screening and the screening laboratory: past, present and future"],"prefix":"10.1530","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-2918","authenticated-orcid":true,"given":"Anita","family":"Boelen","sequence":"first","affiliation":[{"name":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location University of Amsterdam 1 , ,","place":["Amsterdam, The Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism 2 , ,","place":["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":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location University of Amsterdam 1 , ,","place":["Amsterdam, The Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism 2 , ,","place":["Amsterdam, The Netherlands"]},{"name":"Amsterdam Reproduction & Development Research Institute 3 , ,","place":["Amsterdam, The Netherlands"]},{"name":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location Vrije Universiteit Amsterdam 4 , ,","place":["Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"2026070712534101800_bib1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/B978-0-12-820107-7.00010-0","article-title":"Congenital isolated central hypothyroidism: novel mutations and their functional implications","volume":"180","author":"Boelen","year":"2021","journal-title":"Handb Clin Neurol"},{"key":"2026070712534101800_bib2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1177\/095952875003300123","article-title":"Two cases of absence of the thyroid body, and symmetrical swellings of fat tissue at the sides of the neck, connected with defective cerebral development","volume":"33","author":"Curling","year":"1850","journal-title":"Med Chir Trans"},{"key":"2026070712534101800_bib3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/095952877105400108","article-title":"On sporadic cretinism, occurring in england","volume":"54","author":"Fagge","year":"1871","journal-title":"Med Chir Trans"},{"key":"2026070712534101800_bib4","first-page":"254","article-title":"On the extirpation of goitre and its consequences","volume":"29","author":"Kocher","year":"1883","journal-title":"Arch Clin Surg"},{"key":"2026070712534101800_bib5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1136\/bmj.1.1261.419","article-title":"The Brown lectures on pathology","volume":"1","author":"Horsley","year":"1885","journal-title":"Br Med J"},{"key":"2026070712534101800_bib6","first-page":"283","article-title":"Experiments on animals","volume":"68","author":"Paget","year":"1920","journal-title":"Hospital"},{"key":"2026070712534101800_bib7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1515\/bchm2.1896.21.4.319","article-title":"About the normal occurrence of iodine in the animal body [\u00dcber das normale Vorkommen von Jod im Thierk\u00f6rper]","volume":"21","author":"Baumann","year":"1986","journal-title":"Ztschr Phys Chem"},{"key":"2026070712534101800_bib8","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1136\/bmj.2.1606.796","article-title":"Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep","volume":"2","author":"Murray","year":"1891","journal-title":"Br Med J"},{"key":"2026070712534101800_bib9","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1210\/jcem-34-6-938","article-title":"A radioimmunoassay for measurement of thyroxine in unextracted serum","volume":"34","author":"Chopra","year":"1972","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib10","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/adc.46.249.692","article-title":"Cretinism: early diagnosis its relation to mental prognosis","volume":"46","author":"Raiti","year":"1971","journal-title":"Arch Dis Child"},{"key":"2026070712534101800_bib11","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1136\/adc.56.2.134","article-title":"Congenital hypothyroidism in Denmark","volume":"56","author":"Jacobsen","year":"1981","journal-title":"Arch Dis Child"},{"key":"2026070712534101800_bib12","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S0022-3476(75)80349-0","article-title":"Preliminary report on a mass screening program for neonatal hypothyroidism","volume":"86","author":"Dussault","year":"1975","journal-title":"J Pediatr"},{"key":"2026070712534101800_bib13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3390\/ijns7010015","article-title":"Neonatal screening in Europe revisited: an ISNS perspective on the current state and developments since 2010","volume":"7","author":"Loeber","year":"2021","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib14","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/0002-9343(76)90417-4","article-title":"Recommendations for screening programs for congenital hypothyroidism","volume":"61","author":"Fisher","year":"1976","journal-title":"Am J Med"},{"key":"2026070712534101800_bib15","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.beem.2013.05.008","article-title":"Screening for congenital hypothyroidism: a worldwide view of strategies","volume":"28","author":"Ford","year":"2014","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2026070712534101800_bib16","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1210\/jc.2016-1822","article-title":"Defining the newborn blood spot screening reference interval for TSH: impact of ethnicity","volume":"101","author":"Peters","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib17","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1210\/jc.2018-00658","article-title":"Newborn screening for primary congenital hypothyroidism: estimating test performance at different TSH thresholds","volume":"103","author":"Knowles","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/archdischild-2015-309564","article-title":"Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone &lt;10 mU\/L","volume":"103","author":"Jones","year":"2018","journal-title":"Arch Dis Child"},{"key":"2026070712534101800_bib19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13052-021-01053-0","article-title":"Neonatal screening for congenital hypothyroidism in an italian centre: a 5-years real-life retrospective study","volume":"47","author":"Maggio","year":"2021","journal-title":"Ital J Pediatr"},{"key":"2026070712534101800_bib20","first-page":"816","article-title":"Impact of the reduction in TSH cutoff level to 6 mIU\/L in neonatal screening for congenital hypothyroidism in santa catarina: final results","volume":"64","author":"Nascimento","year":"2021","journal-title":"Arch Endocrinol Metab"},{"key":"2026070712534101800_bib21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3390\/ijns10030052","article-title":"Impact of lowering TSH cut-off on neonatal screening for congenital hypothyroidism in Minas Gerais, Brazil","volume":"10","author":"Teixeira Palla Braga","year":"2024","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/ejendo\/lvad064","article-title":"Neonatal screening for congenital hypothyroidism in Sweden 1980\u20132013: effects of lowering the thyroid-stimulating hormone threshold","volume":"188","author":"Gunnerbeck","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib23","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jpeds.2017.09.003","article-title":"Newborn screening in the US may miss mild persistent hypothyroidism","volume":"192","author":"Kilberg","year":"2018","journal-title":"J Pediatr"},{"key":"2026070712534101800_bib24","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1089\/thy.2023.0114","article-title":"Thyrotropin screening of newborns: before or after 72 hours of life? before discharge or at home?","volume":"33","author":"Boros","year":"2023","journal-title":"Thyroid"},{"key":"2026070712534101800_bib25","doi-asserted-by":"crossref","first-page":"e338","DOI":"10.1210\/clinem\/dgaa789","article-title":"Newborn screening for congenital hypothyroidism: the benefit of using differential TSH cutoffs in a 2-screen program","volume":"106","author":"Caiulo","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jpeds.2021.11.003","article-title":"Utility of repeat testing for congenital hypothyroidism in infants with very low birth weight","volume":"242","author":"Rose","year":"2022","journal-title":"J Pediatr"},{"key":"2026070712534101800_bib27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/ijns7040081","article-title":"Targeted secondary screening for congenital hypothyroidism in high-risk neonates: a 9 year review in a large California health care system","volume":"7","author":"Cortez","year":"2021","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib28","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jpeds.2018.11.044","article-title":"Increased congenital hypothyroidism detection in preterm infants with serial newborn screening","volume":"207","author":"Kaluarachchi","year":"2019","journal-title":"J Pediatr"},{"key":"2026070712534101800_bib29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jpeds.2018.09.044","article-title":"Optimal timing of repeat newborn screening for congenital hypothyroidism in preterm infants to detect delayed thyroid-stimulating hormone elevation","volume":"205","author":"McGrath","year":"2019","journal-title":"J Pediatr"},{"key":"2026070712534101800_bib30","doi-asserted-by":"crossref","first-page":"e3329","DOI":"10.1210\/clinem\/dgaa415","article-title":"Newborn screening TSH values less than 15 mIU\/L are not associated with long-term hypothyroidism or cognitive impairment","volume":"105","author":"West","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib31","doi-asserted-by":"crossref","first-page":"D1","DOI":"10.1530\/EJE-17-0107","article-title":"Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?","volume":"177","author":"Lain","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1530\/EJE-19-1048","article-title":"Critical evaluation of the newborn screening for congenital hypothyroidism in the Netherlands","volume":"183","author":"Stroek","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib33","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1159\/000513516","article-title":"Improving the Dutch newborn screening for central congenital hypothyroidism by using 95% reference intervals for thyroxine-binding globulin","volume":"10","author":"Stroek","year":"2021","journal-title":"Eur Thyroid J"},{"key":"2026070712534101800_bib34","doi-asserted-by":"crossref","DOI":"10.1530\/ETJ-23-0041","article-title":"Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?","volume":"12","author":"Boelen","year":"2023","journal-title":"Eur Thyroid J"},{"key":"2026070712534101800_bib35","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1159\/000479367","article-title":"Detecting congenital central hypothyroidism by newborn screening: difficulty in distinguishing from congenital thyroxine-binding globulin deficiency","volume":"88","author":"Connelly","year":"2017","journal-title":"Horm Res Paediatr"},{"key":"2026070712534101800_bib36","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1824-7288-35-2","article-title":"The Italian national register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism","volume":"35","author":"Olivieri","year":"2009","journal-title":"Ital J Pediatr"},{"key":"2026070712534101800_bib37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/096914130301100103","article-title":"Diagnostic effectiveness of simultaneous thyroxine and thyroid-stimulating hormone screening measurements. Thirteen years' experience in the Northeast Italian screening programme","volume":"11","author":"Zamboni","year":"2004","journal-title":"J Med Screen"},{"key":"2026070712534101800_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2021.686317","article-title":"Diagnosis and management of central congenital hypothyroidism","volume":"12","author":"Lauffer","year":"2021","journal-title":"Front Endocrinol"},{"key":"2026070712534101800_bib39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1530\/EJE-11-0653","article-title":"Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper","volume":"166","author":"Adachi","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib40","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1507\/endocrj.EJ14-0143","article-title":"Overall usefulness of newborn screening for congenital hypothyroidism by using free thyroxine measurement","volume":"61","author":"Soneda","year":"2014","journal-title":"Endocr J"},{"key":"2026070712534101800_bib41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cca.2013.04.004","article-title":"Measuring free thyroxine levels in neonatal heel-prick samples","volume":"423","author":"Boelen","year":"2013","journal-title":"Clin Chim Acta"},{"key":"2026070712534101800_bib42","first-page":"250","article-title":"Opportunities and challenges in machine learning-based newborn screening \u2013 a systematic literature review","volume":"63","author":"Zaunseder","year":"2022","journal-title":"JIMD Rep"},{"key":"2026070712534101800_bib43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1210\/clinem\/dgac555","article-title":"Plasma metabolomics reveals systemic metabolic alterations of subclinical and clinical hypothyroidism","volume":"108","author":"Shao","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712534101800_bib44","doi-asserted-by":"crossref","DOI":"10.1530\/ETJ-23-0141","article-title":"Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model","volume":"12","author":"Jansen","year":"2023","journal-title":"Eur Thyroid J"},{"key":"2026070712534101800_bib45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/ijns7020023","article-title":"A novel approach to improve newborn screening for congenital hypothyroidism by integrating covariate-adjusted results of different tests into CLIR customized interpretive tools","volume":"7","author":"Rowe","year":"2021","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib46","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jcf.2023.09.001","article-title":"Optimization of performance of Dutch newborn screening for cystic fibrosis","volume":"23","author":"Bouva","year":"2024","journal-title":"J Cyst Fibros"},{"key":"2026070712534101800_bib47","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3389\/fcell.2020.00499","article-title":"Adrenoleukodystrophy newborn screening in the Netherlands (scan study): the X-factor","volume":"8","author":"Barendsen","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026070712534101800_bib48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3390\/ijns4040040","article-title":"Introducing newborn screening for severe combined immunodeficiency (SCID) in the Dutch neonatal screening program","volume":"4","author":"Blom","year":"2018","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib49","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/ijns5020021","article-title":"Validation of a fast, robust, inexpensive, two-tiered neonatal screening test algorithm on dried blood spots for spinal muscular atrophy","volume":"5","author":"Strunk","year":"2019","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib50","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.ajhg.2022.08.003","article-title":"A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases","volume":"109","author":"Kingsmore","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2026070712534101800_bib51","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1286747","article-title":"Borealin\/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures","volume":"14","author":"Didier-Mathon","year":"2023","journal-title":"Front Endocrinol"},{"key":"2026070712534101800_bib52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40618-017-0715-x","article-title":"Role of Jagged1-Notch pathway in thyroid development","volume":"41","author":"Marelli","year":"2018","journal-title":"J Endocrinol Invest"},{"key":"2026070712534101800_bib53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12020-022-03188-4","article-title":"Mutation screening of eight genes and comparison of the clinical data in a Chinese cohort with congenital hypothyroidism","volume":"79","author":"Li","year":"2023","journal-title":"Endocrine"},{"key":"2026070712534101800_bib54","doi-asserted-by":"crossref","first-page":"K1","DOI":"10.1530\/EJE-20-0255","article-title":"First case of fetal goitrous hypothyroidism due to SLC5A5\/NIS mutations","volume":"183","author":"Stoupa","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib55","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.99631","article-title":"Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism","volume":"3","author":"Cangul","year":"2018","journal-title":"JCI Insight"},{"key":"2026070712534101800_bib56","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1530\/EJE-20-0833","article-title":"Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening","volume":"183","author":"Naafs","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"2026070712534101800_bib57","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2023.1185802","article-title":"Combined genetic screening and traditional newborn screening to improve the screening efficiency of congenital hypothyroidism","volume":"11","author":"Ye","year":"2023","journal-title":"Front Pediatr"},{"key":"2026070712534101800_bib58","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3390\/ijns10010018","article-title":"Psychosocial impact of a true-positive, false-positive, or inconclusive newborn bloodspot screening result: a questionnaire study among parents","volume":"10","author":"van den Heuvel","year":"2024","journal-title":"Int J Neonatal Screen"},{"key":"2026070712534101800_bib59","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1001\/jama.290.19.2564","article-title":"Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress","volume":"290","author":"Waisbren","year":"2003","journal-title":"JAMA"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/etj.bioscientifica.com\/view\/journals\/etj\/14\/1\/ETJ-24-0325.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/etj.bioscientifica.com\/downloadpdf\/journals\/etj\/14\/1\/ETJ-24-0325.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-24-0325\/32729\/etj-24-0325.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-24-0325\/32729\/etj-24-0325.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:22:02Z","timestamp":1783444922000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/14\/1\/e240325\/4396\/Newborn-screening-and-the-screening-laboratory"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2,1]]}},"URL":"https:\/\/doi.org\/10.1530\/etj-24-0325","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,24]]},"article-number":"e240325"}}