{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:29:15Z","timestamp":1771399755902,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to examine the effect of maternal isolated hypothyroxinemia (IH) during early pregnancy on the neuropsychological development of the offspring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single-center prospective cohort study included 100 mother\u2013child pairs, with 50 pairs in the IH group and an equal number in the euthyroid group. Levels of free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibody in maternal serum were measured during the first trimester. Offspring neurodevelopment was evaluated using the Chinese Developmental Scale for Children Aged 0\u20136 Years (2\n                      <jats:sup>nd<\/jats:sup>\n                      Edition), Conners Parent Symptom Questionnaire, and Social Responsiveness Scale (SRS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After adjusting for confounding factors, multiple linear regression analysis indicated that maternal IH in the first trimester was significantly associated with a decreased developmental quotient in the offspring (adjusted \u03b2 = \u22123.28, 95% CI: \u22125.09 to \u22121.47, P &amp;lt; 0.001). The highest association was observed in the language domain (adjusted \u03b2 = \u22125.72, 95% CI: \u22128.00 to \u22123.43, P &amp;lt; 0.001). Moreover, first-trimester IH exposure was linked to increased scores on the offspring\u2019s impulsive\u2013hyperactive behavior (adjusted \u03b2 = 0.38, 95% CI: 0.16\u20130.60, P = 0.001) and hyperactivity index (adjusted \u03b2 = 0.23, 95% CI: 0.06\u20130.41, P = 0.011). In addition, the offspring\u2019s social awareness (adjusted \u03b2 = 1.21, 95% CI: 0.10\u20132.31, P = 0.035) and social communication (adjusted \u03b2 = 3.01, 95% CI: 0.50\u20135.53, P = 0.021) subscale scores as well as the total SRS score (adjusted \u03b2 = 6.51, 95% CI: 0.33\u201312.69, P = 0.042) were elevated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Maternal IH in the first trimester is associated with lower intellectual developmental scores and higher scores on screening scales for symptoms related to attention-deficit\/hyperactivity disorder and autism spectrum disorder in the offspring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1734708","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:55:11Z","timestamp":1771397711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of maternal isolated hypothyroxinemia in the first trimester on offspring neurodevelopment: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2024.0512","article-title":"Mild gestational hypothyroidism in mice has transient developmental effects and long-term consequences on neuroendocrine systems","volume":"35","author":"Quignon","year":"2024","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-005-3053-9","article-title":"Thyroid development and effect on the nervous system","volume":"6","author":"Santisteban","year":"2005","journal-title":"Rev Endocr Metab Disord"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/2025.05.14.654075","article-title":"Thyroid hormone promotes fetal neurogenesis","volume":"10","author":"Salas-Lucia","year":"2025","journal-title":"JCI Insight"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/JOE-10-0444","article-title":"Thyroid hormones and fetal neurological development","volume":"209","author":"Patel","year":"2011","journal-title":"J Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2019.09.005","article-title":"Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic","volume":"58","author":"L\u00f3pez-Mu\u00f1oz","year":"2019","journal-title":"Taiwan J Obstet Gynecol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198907063210103","article-title":"Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis","volume":"321","author":"Vulsma","year":"1989","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13550","article-title":"Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis","volume":"88","author":"Thompson","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/nan.12074","article-title":"Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar Purkinje cells in rat offspring: involvement of microtubule-associated protein 2 (MAP2) and stathmin","volume":"40","author":"Wang","year":"2014","journal-title":"Neuropathol Appl Neurobiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2004.03.012","article-title":"Maternal thyroid hormones early in pregnancy and fetal brain development","volume":"18","author":"de Escobar","year":"2004","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01733.x","article-title":"Neurodevelopmental and neurophysiological actions of thyroid hormone","volume":"20","author":"Williams","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114790","article-title":"Congenital hypothyroidism, as studied in rats. 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