{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:32:58Z","timestamp":1787502778340,"version":"build-2736575974"},"reference-count":36,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government","award":["NRF2020R1F1A1076452"],"award-info":[{"award-number":["NRF2020R1F1A1076452"]}]},{"name":"Korea Health Technology R&D Project"},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["HR22C1605030022"],"award-info":[{"award-number":["HR22C1605030022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages &amp; Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score\u2013weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction &amp;gt;.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgad364","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T16:07:59Z","timestamp":1687190879000},"page":"e1588-e1596","source":"Crossref","is-referenced-by-count":12,"title":["Assessment of Neurodevelopment and Growth in Congenital Hypothyroidism: Serial 6-Year Follow-up Study of 408 Patients"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-5729","authenticated-orcid":false,"given":"Eun Kyo","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital , 07441 Seoul , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4945-0753","authenticated-orcid":false,"given":"Ju Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kyung Hee University Hospital, Kyung Hee University School of Medicine , 02447 Seoul , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ryeong","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Sungkyunkwan University , 16419 Suwon , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Chun","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Konkuk University , 05029 Seoul , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-4013","authenticated-orcid":false,"given":"Jeewon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHA Bundang Medical Center, CHA University , 13496 Seongnam , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School , 61469 Gwangju , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHA Ilsan Medical Center, CHA University , 10414 Goyang , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Gyong","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHA Bundang Medical Center, CHA University , 13496 Seongnam , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5904-4946","authenticated-orcid":false,"given":"Mo Kyung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHA Bundang Medical Center, CHA University , 13496 Seongnam , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-5779","authenticated-orcid":false,"given":"Man Yong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHA Bundang Medical Center, CHA University , 13496 Seongnam , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"issue":"1","key":"2023111712401539200_dgad364-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clp.2017.10.004","article-title":"Congenital hypothyroidism","volume":"45","author":"Wassner","year":"2018","journal-title":"Clin Perinatol"},{"issue":"2","key":"2023111712401539200_dgad364-B2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1203\/PDR.0b013e31818d2030","article-title":"Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment","volume":"65","author":"Dimitropoulos","year":"2009","journal-title":"Pediatr Res"},{"issue":"4","key":"2023111712401539200_dgad364-B3","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1136\/adc.2010.190280","article-title":"Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level?","volume":"96","author":"Grosse","year":"2011","journal-title":"Arch Dis Child"},{"issue":"5","key":"2023111712401539200_dgad364-B4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/MED.0000000000000181","article-title":"Congenital hypothyroidism: recent advances","volume":"22","author":"Wassner","year":"2015","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"issue":"3","key":"2023111712401539200_dgad364-B5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1203\/00006450-199603000-00028","article-title":"Neuropsychologic development in early treated congenital hypothyroidism: analysis of literature data","volume":"39","author":"Derksen-Lubsen","year":"1996","journal-title":"Pediatr Res"},{"issue":"3","key":"2023111712401539200_dgad364-B6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/thy.2000.10.243","article-title":"Neuropsychological follow-up in early-treated congenital hypothyroidism: a problem-oriented approach","volume":"10","author":"Bargagna","year":"2000","journal-title":"Thyroid"},{"issue":"4","key":"2023111712401539200_dgad364-B7","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1542\/peds.112.4.923","article-title":"Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults","volume":"112","author":"Oerbeck","year":"2003","journal-title":"Pediatrics"},{"issue":"3","key":"2023111712401539200_dgad364-B8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1210\/jc.2006-1538","article-title":"Neonatal screening for congenital hypothyroidism in The Netherlands: cognitive and motor outcome at 10 years of age","volume":"92","author":"Kempers","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2023111712401539200_dgad364-B9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1507\/endocrj.K10E-384","article-title":"Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment","volume":"58","author":"Huo","year":"2011","journal-title":"Endocr J"},{"issue":"3","key":"2023111712401539200_dgad364-B10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1067\/mpd.2000.103351","article-title":"Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism","volume":"136","author":"Bongers-Schokking","year":"2000","journal-title":"J Pediatr"},{"issue":"9","key":"2023111712401539200_dgad364-B11","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1210\/jc.2013-1903","article-title":"Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring","volume":"98","author":"Albert","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2023111712401539200_dgad364-B12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/0009922806289326","article-title":"Mental development of infants with congenital hypothyroidism: a longitudinal study","volume":"46","author":"Nakamizo","year":"2007","journal-title":"Clin Pediatr (Phila)"},{"issue":"1","key":"2023111712401539200_dgad364-B13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13052-015-0190-y","article-title":"Final height in Italian patients with congenital hypothyroidism detected by neonatal screening: a 20-year observational study","volume":"41","author":"Delvecchio","year":"2015","journal-title":"Ital J Pediatr"},{"issue":"4","key":"2023111712401539200_dgad364-B14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1530\/eje.0.1450377","article-title":"Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening","volume":"145","author":"Salerno","year":"2001","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2023111712401539200_dgad364-B15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1046\/j.1365-2265.1998.3791206.x","article-title":"Congenital hypothyroidism in Wales (1982-1993): demographic features, clinical presentation and effects on early neurodevelopment","volume":"48","author":"Law","year":"1998","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"2023111712401539200_dgad364-B16","doi-asserted-by":"crossref","first-page":"565","DOI":"10.4103\/2230-8210.98012","article-title":"Linear growth and neurodevelopmental outcome of children with congenital hypothyroidism detected by neonatal screening: a controlled study","volume":"16","author":"Soliman","year":"2012","journal-title":"Indian J Endocrinol Metab"},{"issue":"6","key":"2023111712401539200_dgad364-B17","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.jpeds.2005.07.024","article-title":"Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH","volume":"147","author":"Selva","year":"2005","journal-title":"J Pediatr"},{"issue":"2","key":"2023111712401539200_dgad364-B18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tics.2008.11.003","article-title":"Socioeconomic status and the developing brain","volume":"13","author":"Hackman","year":"2009","journal-title":"Trends Cogn Sci"},{"issue":"11","key":"2023111712401539200_dgad364-B19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0205955","article-title":"The effect of neonatal hypothyroidism and low family income on intellectual disability: a population-based cohort study","volume":"13","author":"Nam","year":"2018","journal-title":"PLoS One"},{"issue":"9","key":"2023111712401539200_dgad364-B20","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3345\/cep.2020.01284","article-title":"Cohort profile: national investigation of birth cohort in Korea study 2008 (NICKs-2008)","volume":"64","author":"Kim","year":"2021","journal-title":"Clin Exp Pediatr"},{"issue":"1","key":"2023111712401539200_dgad364-B21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3345\/cep.2021.00248","article-title":"Worldwide national intervention of developmental screening programs in infant and early childhood","volume":"65","author":"Kim","year":"2022","journal-title":"Clin Exp Pediatr"},{"key":"2023111712401539200_dgad364-B22","author":"Ha"},{"issue":"6","key":"2023111712401539200_dgad364-B23","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3345\/cep.2021.01417","article-title":"Neurodevelopmental outcomes and comorbidities of children with congenital muscular torticollis: evaluation using the National Health Screening Program for Infants and Children database","volume":"65","author":"Kim","year":"2022","journal-title":"Clin Exp Pediatr"},{"issue":"2","key":"2023111712401539200_dgad364-B24","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"},{"issue":"3","key":"2023111712401539200_dgad364-B25","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/jhn.13098","article-title":"Association between complementary food introduction before age 4 months and body mass index at age 5-7 years: a retrospective population-based longitudinal cohort study","volume":"36","author":"Ha","year":"2022","journal-title":"J Hum Nutr Diet"},{"issue":"2","key":"2023111712401539200_dgad364-B26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2188\/jea.JE20120113","article-title":"Epidemiology and clinical characteristics of congenital hypothyroidism in an Asian population: a nationwide population-based study","volume":"23","author":"Chen","year":"2013","journal-title":"J Epidemiol"},{"issue":"1","key":"2023111712401539200_dgad364-B27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J Rare Dis"},{"issue":"8","key":"2023111712401539200_dgad364-B28","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1111\/j.1460-9568.2004.03664.x","article-title":"Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat","volume":"20","author":"Fernandez","year":"2004","journal-title":"Eur J Neurosci"},{"issue":"11","key":"2023111712401539200_dgad364-B29","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1210\/jc.2013-2175","article-title":"Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment?","volume":"98","author":"Bongers-Schokking","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2023111712401539200_dgad364-B30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s12020-016-1010-x","article-title":"Growth development in children with congenital hypothyroidism: the effect of screening and treatment variables-a comprehensive longitudinal study","volume":"54","author":"Heidari","year":"2016","journal-title":"Endocrine"},{"issue":"1","key":"2023111712401539200_dgad364-B31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/tropej\/fmr010","article-title":"Long-term consequences of the early treatment of children with congenital hypothyroidism detected by neonatal screening in Nanjing, China: a 12-year follow-up study","volume":"58","author":"Sun","year":"2012","journal-title":"J Trop Pediatr"},{"issue":"Suppl 1","key":"2023111712401539200_dgad364-B32","first-page":"8","article-title":"Newborn screening for congenital hypothyroidism","volume":"5","author":"B\u00fcy\u00fckgebiz","year":"2013","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"2023111712401539200_dgad364-B33","doi-asserted-by":"crossref","first-page":"463939","DOI":"10.1155\/2013\/463939","article-title":"Growth and specialized growth charts of children with congenital hypothyroidism detected by neonatal screening in Isfahan, Iran","volume":"2013","author":"Feizi","year":"2013","journal-title":"ISRN Endocrinol"},{"issue":"6","key":"2023111712401539200_dgad364-B34","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1651-2227.2003.tb00603.x","article-title":"Final height and pubertal growth in Japanese patients with congenital hypothyroidism detected by neonatal screening","volume":"92","author":"Adachi","year":"2003","journal-title":"Acta Paediatr"},{"issue":"3","key":"2023111712401539200_dgad364-B35","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s12020-015-0574-1","article-title":"Levothyroxine requirement in congenital hypothyroidism: a 12-year longitudinal study","volume":"50","author":"Delvecchio","year":"2015","journal-title":"Endocrine"},{"issue":"5","key":"2023111712401539200_dgad364-B36","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/j.1365-2265.2006.02651.x","article-title":"Factors predicting final height in early treated congenital hypothyroid patients","volume":"65","author":"Delvecchio","year":"2006","journal-title":"Clin Endocrinol (Oxf)"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad364\/50734511\/dgad364.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/12\/e1588\/53480845\/dgad364.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/12\/e1588\/53480845\/dgad364.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T08:41:40Z","timestamp":1700210500000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/12\/e1588\/7202272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,19]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6,19]]},"published-print":{"date-parts":[[2023,11,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad364","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12]]},"published":{"date-parts":[[2023,6,19]]}}}