{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:56:21Z","timestamp":1785826581553,"version":"3.56.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore early management strategies for full-term neonates with TSH 5\u201310 mU\/L and normal FT4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single-center longitudinal prospective study, 88 neonates diagnosed at 7\u201314 days were followed to age three.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>94.3% (83\/88) had transient TSH elevation; 77 normalized within two months without treatment, while six received levothyroxine (3\u20135\u00b5g\/kg\/day). Five neonates (5.7%) exhibited persistent hyperthyrotropinemia and had significantly higher initial TSH. No hyperthyroidism was observed. Following up to 3 years old, only one child (1\/81, 1.2%) exhibited development delay in personal-social development. Neonates with transient hyperthyrotropinaemia scored higher in problem-solving and personal\u2013social domains than those with persistent hyperthyrotropinaemia. Neonatal FT4 at 7\u201314 days, timing of TSH normalization, and maternal early-pregnancy FT4 influenced the neurodevelopment of neonates. Infants of mothers with gestational diabetes scored lower in the personal\u2013social domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Persistent hyperthyrotropinemia occurs in 5.7% of mild cases and is associated with higher initial TSH. Levothyroxine at 3\u20135 \u00b5g\/kg\/day is both adequate and safe. The majority of neonates got a normal neurodevelopment by age 3, and the subtle difference between transient and persistent hyperthyrotropinemia was impacted by both maternal and neonatal factors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1548086","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:10:42Z","timestamp":1751515842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-center prospective study on thyroid function outcomes and neurological prognoses at 3 years of age in children with mild neonatal hyperthyrotropinemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Guoyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zezhong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1089\/thy.2020.0333","article-title":"Congenital hypothyroidism: A 2020\u20132021 consensus guidelines update -an ENDO-European reference network initiative endorsed by the European society for pediatric endocrinology and the European society for endocrinology","volume":"31","author":"van Trotsenburg","year":"2021","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","first-page":"643307","DOI":"10.3389\/fendo.2021.643307","article-title":"Update on neonatal isolated hyperthyrotropinemia A systematic review","volume":"12","author":"Chiesa","year":"2021","journal-title":"Front Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2017.05.003","article-title":"Neonatal screening: 9% of children with filter paper thyroid-stimulating hormone levels between 5 and 10 IU\/mL have congenital hypothyroidism","volume":"93","author":"Christensen-Adad","year":"2017","journal-title":"J Pediatr (Rio J)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022-060420","article-title":"Congenital hypothyroidism: screening and management","volume":"151","author":"Rose","year":"2023","journal-title":"Pediatrics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1297\/cpe.2022-0063","article-title":"Guidelines for newborn screening of congenital hypothyroidism (2021 revision)","volume":"32","author":"Nagasaki","year":"2023","journal-title":"Clin Pediatr Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1310.2011.06.006","article-title":"Consensus on the diagnosis and treatment of congenital hypothyroidism","volume":"49","year":"2011","journal-title":"Chin J Pediatr"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30122-X","article-title":"Association between borderline neonatal thyroid-stimulating hormone concentrations and educational and developmental outcomes: a population-based record-linkage study","volume":"4","author":"Lain","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0002-22.2022","article-title":"Tsh induces agrp1 neuron proliferation in oatp1c1-deficient zebrafish","volume":"42","author":"Wasserman-Bartov","year":"2022","journal-title":"J Neurosci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/cch.12397","article-title":"The psychometric properties of the ages & stages questionnaires for ages 2\u201325: a systematic review","volume":"43","author":"Velikonja","year":"2017","journal-title":"Child Care Health Dev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.bmhimx.2016.07.008","article-title":"Ages and Stages Questionnaire: a global screening scale","volume":"74","author":"Singh","year":"2017","journal-title":"Bol Med Hosp Infant Mex"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn311282-20220416-00234","article-title":"Women\u2019s health branch of the Chinese preventive medicine association. Guidelines for the prevention and management of thyroid diseases during pregnancy and postpartum","volume":"38","year":"2022","journal-title":"Chin J Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4274\/Jcrpe.931","article-title":"The role of initial clinical and laboratory findings in infants with hyperthyrotropinemia to predict transient or permanent hypothyroidism","volume":"5","author":"Un\u00fcvar","year":"2013","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jpeds.2016.04.011","article-title":"Can one predict resolution of neonatal hyperthyrotropinemia","volume":"174","author":"Aguiar","year":"2016","journal-title":"J Pediatr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309564","article-title":"Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone<10 mU\/L","volume":"103","author":"Jones","year":"2018","journal-title":"Arch Dis Child"},{"key":"B15","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1111\/j.1365-2265.2005.02239.x","article-title":"Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study","volume":"62","author":"Gaudino","year":"2005","journal-title":"J Clin Endocrinol Metab (Oxf)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28091","article-title":"Malignancy and lymphoid proliferation in primary immune deficiencies; hard to define, hard to treat","volume":"67","author":"Kiykim","year":"2020","journal-title":"Pediatr Blood Cancer"},{"key":"B17","first-page":"1","article-title":"TSH receptor gene mutations and thyroid dysplasia","volume":"17","author":"Jie","year":"2021","journal-title":"J Pract Diabetes"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.10.7959","article-title":"Subclinical hypothyroidism is mild thyroid failure and should be treated","volume":"86","author":"McDermott","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.50.379","article-title":"Persistence of mild hyperthyrotropinemia after discontinuation of three-year course of low-dose L-thyroxine therapy in infants with borderline hypothyroidism","volume":"50","author":"Tomita","year":"2003","journal-title":"Endocr J"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03634.x","article-title":"Neonatal hyperthyrotropinemia: population characteristics, diagnosis, management and outcome after cessation of therapy","volume":"72","author":"Zung","year":"2010","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2006.00998.x","article-title":"L-thyroxine treatment in infants with hyperthyrotropinemia: 4 year experience","volume":"61","author":"Demirel","year":"2007","journal-title":"Int J Clin Pract"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102213240805","article-title":"Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus","volume":"324","author":"Thorpe-Beeston","year":"1991","journal-title":"N Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac57724","article-title":"Maternal thyroid dysfunction and neuropsychological development in children","volume":"108","author":"Chen","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S2213-8587(15)00327-7","article-title":"Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study","volume":"4","author":"Korevaar","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.04.01126","article-title":"Reduced cortical excitability, neuroplasticity, and salivary cortisol in 11-13-year-old children born to women with gestational diabetes mellitus","volume":"31","author":"Van Dam","year":"2018","journal-title":"EBioMedicine"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1125628","article-title":"The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence","volume":"14","author":"Rodolaki","year":"2023","journal-title":"Front Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1548086\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:10:44Z","timestamp":1751515844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1548086\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,3]]},"references-count":26,"alternative-id":["10.3389\/fendo.2025.1548086"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1548086","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,3]]},"article-number":"1548086"}}