{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T19:11:42Z","timestamp":1780686702843,"version":"3.54.1"},"reference-count":32,"publisher":"Walter de Gruyter GmbH","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-1387_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Newborn screening for congenital hypothyroidism (CH) relies on thyroid-stimulating hormone (TSH) levels from dried blood spots (DBS). We investigated whether incorporating TSH variation across serial DBS could improve prediction of CH in term and preterm infants with complex risk profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1387_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Among 207,895 newborns screened, 272 (0.13\u202f%) were diagnosed with CH. TSH variations across 3 serial DBS were analyzed in 6,146 healthy infants (2.96\u202f%). Predictive algorithms were developed using linear mixed-effects models in 1,968 term and 1,387 preterm infants with\u00a0\u22652 and\u00a0\u22653 DBS, respectively. Average DBS collection times were 58, 260, and 478\u202fh for term and 63, 350, and 664\u202fh for preterm infants. TSH was measured by GSP neonatal hTSH assay (Revvity).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1387_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Daily TSH variation was influenced by the initial DBS1 value. For DBS1 &gt;5.2 and &lt;1.7\u202fmUI\/L, increase and decrease, respectively, in TSH level on DBS2 is detectable, and this particularly occurs in preterm infants. In preterms, CH could be excluded when TSH remained &lt;5\u202fmUI\/L on DBS1,\u00a0&lt;6\u202fmUI\/L on DBS2, &lt;4\u202fmUI\/L on DBS3, and with daily variation &lt;12\u202f% from DBS1 to DBS3 (sensitivity 100\u202f%; specificity 77.85\u202f%). Term infants with TSH &lt;11\u202fmUI\/L on DBS1, &lt;4.5\u202fmUI\/L on DBS2, and daily variation &lt;13\u202f% from DBS1 to DBS2 may be ruled out for CH (sensitivity 96.5\u202f%; specificity 66.6\u202f%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-1387_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Distinct predictive algorithms for term and preterm newborns, incorporating TSH variations as daily percentage changes, may improve CH rule out in children with complex risk profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-1387","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:57:17Z","timestamp":1769525837000},"page":"1604-1613","source":"Crossref","is-referenced-by-count":0,"title":["Predicting congenital hypothyroidism in newborns with complex risk profiles by using thyroid-stimulating hormone variations across serial dried blood spots"],"prefix":"10.1515","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2863-5596","authenticated-orcid":false,"given":"Laura","family":"Cappelletti","sequence":"first","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Gaviglio","sequence":"additional","affiliation":[{"name":"Connetics Consulting, LLC , Minneapolis , MN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Moggia","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology, and Public Health, Department of Statistics and Quantitative Methods , University of Milano-Bicocca , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Lalli","sequence":"additional","affiliation":[{"name":"Unit of Translational Immunology , Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Fede","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Cannella","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Vigone","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , IRCCS San Raffaele Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianvincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science , University of Milan , Milan , Italy"},{"name":"Department of Pediatrics , Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Zambon","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology, and Public Health, Department of Statistics and Quantitative Methods , University of Milano-Bicocca , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cereda","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6733-4166","authenticated-orcid":false,"given":"Simona","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital , Milan , Italy"},{"name":"Department of Pediatrics , Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"2026060518413043254_j_cclm-2025-1387_ref_001","unstructured":"Bowden, SA, Goldis, M. Congenital hypothyroidism. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK558913\/ [Accessed 5 Jun 2023]."},{"key":"2026060518413043254_j_cclm-2025-1387_ref_002","doi-asserted-by":"crossref","unstructured":"Kollati, Y, Akella, RRD, Naushad, SM, Thalla, M, Reddy, GB, Dirisala, VR, et al.. The rs1991517 polymorphism is a genetic risk factor for congenital hypothyroidism. Biotech 2020;10:285. https:\/\/doi.org\/10.1007\/s13205-020-02273-7.","DOI":"10.1007\/s13205-020-02273-7"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_003","doi-asserted-by":"crossref","unstructured":"Grob, F, Lain, S, Olivieri, A. Newborn screening for primary congenital hypothyroidism: past, present and future. Eur Thyroid J 2025;14. https:\/\/doi.org\/10.1530\/etj-24-0358.","DOI":"10.1530\/ETJ-24-0358"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_004","doi-asserted-by":"crossref","unstructured":"Delado\u00eby, J, Ruel, J, Gigu\u00e8re, Y, Van Vliet, G. Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Qu\u00e9bec. J\u00a0Clin Endocrinol Metab 2011;96:2422\u20139.","DOI":"10.1210\/jc.2011-1073"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_005","doi-asserted-by":"crossref","unstructured":"Hinton, CF, Harris, KB, Borgfeld, L, Drummond-Borg, M, Eaton, R, Lorey, F, et al.. Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United\u00a0States, California, Massachusetts, New York, and Texas. Pediatrics 2010;125:S37\u201347. https:\/\/doi.org\/10.1542\/peds.2009-1975d.","DOI":"10.1542\/peds.2009-1975D"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_006","unstructured":"Strahan, JE, Canfield, MA, Drummond-Borg, LM, Neill, SU. Ethnic and gender patterns for the five congenital disorders in Texas from 1992 through 1998. Tex Med 2002;98:80\u20136."},{"key":"2026060518413043254_j_cclm-2025-1387_ref_007","doi-asserted-by":"crossref","unstructured":"Waller, DK, Anderson, JL, Lorey, F, Cunningham, GC. Risk factors for congenital hypothyroidism: an investigation of infant\u2019s birth weight, ethnicity, and gender in California, 1990\u20131998. Teratology2000;62:36\u201341. https:\/\/doi.org\/10.1002\/1096-9926(200007)62:1<36::aid-tera8>3.3.co;2-n.","DOI":"10.1002\/1096-9926(200007)62:1<36::AID-TERA8>3.3.CO;2-N"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_008","doi-asserted-by":"crossref","unstructured":"Yu, A, Alder, N, Lain, SJ, Wiley, V, Nassar, N, Jack, M, et al.. Outcomes of lowered newborn screening thresholds for congenital hypothyroidism. 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Hyperthyrotropinemia is common in preterm infants who are born small for gestational age. J\u00a0Pediatr Endocrinol Metab 2020;33:375\u201382. https:\/\/doi.org\/10.1515\/jpem-2019-0461.","DOI":"10.1515\/jpem-2019-0461"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_012","doi-asserted-by":"crossref","unstructured":"Nolan, B, Uy, C, Stablein, L, Bany-Mohammed, F. Screening for delayed thyroid stimulation hormone rise and atypical congenital hypothyroidism in infants born very preterm and infants with very low birth weight. J\u00a0Pediatr 2024;269. https:\/\/doi.org\/10.1016\/j.jpeds.2024.113974.","DOI":"10.1016\/j.jpeds.2024.113974"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_013","doi-asserted-by":"crossref","unstructured":"Rapaport, R, Rose, SR, Freemark, M. Hypothyroxinemia in the preterm infant: the benefits and risks of thyroxine treatment. 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J\u00a0Inherit Metab Dis 2006;29:677\u201382. https:\/\/doi.org\/10.1007\/s10545-006-0381-1.","DOI":"10.1007\/s10545-006-0381-1"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_026","doi-asserted-by":"crossref","unstructured":"Caiulo, S, Corbetta, C, Di Frenna, M, Medda, E, De Angelis, S, Rotondi, D, et al.. Newborn screening for congenital hypothyroidism: the benefit of using differential TSH cutoffs in a 2-screen program. J\u00a0Clin Endocrinol Metab 2021;106:e338\u201349. https:\/\/doi.org\/10.1210\/clinem\/dgaa789.","DOI":"10.1210\/clinem\/dgaa789"},{"key":"2026060518413043254_j_cclm-2025-1387_ref_027","doi-asserted-by":"crossref","unstructured":"Olivieri, A, Fazzini, C, Medda, E. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. 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