{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:14:41Z","timestamp":1793110481178,"version":"4.5.0"},"reference-count":40,"publisher":"BMJ","issue":"1","funder":[{"name":"Greek Ministry of Health","award":["Program of Prevention of obesity and neurodevelopm"],"award-info":[{"award-number":["Program of Prevention of obesity and neurodevelopm"]}]},{"name":"Greek Ministry of Health","award":["\u201cRhea Plus\u201d: Primary Prevention Program of Env"],"award-info":[{"award-number":["\u201cRhea Plus\u201d: Primary Prevention Program of Env"]}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP6-2003-Food-3-NewGeneris"],"award-info":[{"award-number":["EU FP6-2003-Food-3-NewGeneris"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP6. STREP Hiwate"],"award-info":[{"award-number":["EU FP6. STREP Hiwate"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape"],"award-info":[{"award-number":["EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIEC"],"award-info":[{"award-number":["EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIEC"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers"],"award-info":[{"award-number":["EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP7-HEALTH-2009 - single stage CHICOS"],"award-info":[{"award-number":["EU FP7-HEALTH-2009 - single stage CHICOS"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EU FP7.2007-2013- Project No 308333-The Helix Proj"],"award-info":[{"award-number":["EU FP7.2007-2013- Project No 308333-The Helix Proj"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Epidemiol Community Health"],"accepted":{"date-parts":[[2020,8,12]]},"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec id=\"s1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Maternal thyroid hormones\u2019 supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s2\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 757 mother\u2013child pairs from the prospective \u2018Rhea\u2019 cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14\u00a0weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18\u00a0months of age), McCarthy Scales of Children\u2019s Abilities (4\u00a0years of age), Raven\u2019s Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6\u00a0years of age).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s3\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4\u00a0years and reduced motor speed at 6\u00a0years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4\u00a0years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory (\u2018low\u2019: adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), \u2018high-decreasing\u2019: adjusted RRR = 2.2 95% CI: (1.2, 4.0), \u2018low-increasing\u2019: adjusted RRR = 1.8 95% CI: (1.0, 3.2)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s4\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Maternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jech-2019-213309","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T17:22:36Z","timestamp":1599672156000},"page":"29-35","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother\u2013child cohort study in Crete, Greece"],"prefix":"10.1136","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3359-5691","authenticated-orcid":false,"given":"Mariza","family":"Kampouri","sequence":"first","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Margetaki","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Koutra","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"},{"name":"Department of Psychology, University of Crete School of Social Sciences, Rethimno, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriani","family":"Kyriklaki","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polyxeni","family":"Karakosta","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Anousaki","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Chalkiadaki","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Vafeiadi","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolis","family":"Kogevinas","sequence":"additional","affiliation":[{"name":"Instituto de Salud Global Barcelona, Barcelona, Spain"},{"name":"Hospital del Mar Institute for Medical Research, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Chatzi","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece"},{"name":"Preventive Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"Department of Genetics and Cell Biology, Maastricht University Faculty of Health Medicine and Life Sciences, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"2025100521493075000_75.1.29.1","doi-asserted-by":"publisher","DOI":"10.2307\/3454543"},{"key":"2025100521493075000_75.1.29.2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/ncpendmet0424","article-title":"Thyroid hormone receptors in brain development and function","volume":"3","author":"Bernal","year":"2007","journal-title":"Nat Rev Endocrinol"},{"key":"2025100521493075000_75.1.29.3","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.151U025"},{"key":"2025100521493075000_75.1.29.4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fendo.2016.00016","article-title":"Preliminary findings show maternal hypothyroidism may contribute to abnormal cortical morphology in offspring","volume":"7","author":"Lischinsky","year":"2016","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025100521493075000_75.1.29.5","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1089\/thy.2014.0548","article-title":"Children born to women treated for hypothyroidism during pregnancy show abnormal corpus callosum development","volume":"25","author":"Samadi","year":"2015","journal-title":"Thyroid"},{"key":"2025100521493075000_75.1.29.6","unstructured":"Fuster JM . Cortex and mind: unifying cognition . Oxford University Press, 2003."},{"key":"2025100521493075000_75.1.29.7","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e318276ccd3"},{"key":"2025100521493075000_75.1.29.8","doi-asserted-by":"crossref","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":"2025100521493075000_75.1.29.9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4281"},{"key":"2025100521493075000_75.1.29.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03743.x"},{"key":"2025100521493075000_75.1.29.11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2003.01822.x"},{"key":"2025100521493075000_75.1.29.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2451"},{"key":"2025100521493075000_75.1.29.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2012.07.004"},{"key":"2025100521493075000_75.1.29.14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3389"},{"key":"2025100521493075000_75.1.29.15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0415"},{"key":"2025100521493075000_75.1.29.16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0274"},{"key":"2025100521493075000_75.1.29.17","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1210\/jc.2018-00743","article-title":"The association of maternal thyroid autoimmunity during pregnancy with child IQ","volume":"103","author":"Derakhshan","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2025100521493075000_75.1.29.18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.12.3561"},{"key":"2025100521493075000_75.1.29.19","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/pr.2012.117","article-title":"Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore collaborative perinatal project","volume":"72","author":"Wasserman","year":"2012","journal-title":"Pediatr Res"},{"key":"2025100521493075000_75.1.29.20","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1089\/thy.2011.0318","article-title":"Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit\/hyperactivity problems in children: the generation R study","volume":"22","author":"Ghassabian","year":"2012","journal-title":"Thyroid"},{"key":"2025100521493075000_75.1.29.21","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1093\/ije\/dyx084","article-title":"Cohort profile: the mother-child cohort in Crete, Greece (Rhea Study)","volume":"46","author":"Chatzi","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2025100521493075000_75.1.29.22","doi-asserted-by":"crossref","unstructured":"Karakosta P , Chatzi L , Bagkeris E , et al. First-and second-trimester reference intervals for thyroid hormones during pregnancy in \u201cRhea\u201d mother-child cohort, Crete, Greece. J Thyroid Res 2011;2011. doi: 10.4061\/2011\/490783","DOI":"10.4061\/2011\/490783"},{"key":"2025100521493075000_75.1.29.23","unstructured":"Weiss LG , Oakland T , Aylward GP . Bayley-III Clinical Use and Interpretation . Academic Press, 2010."},{"key":"2025100521493075000_75.1.29.24","doi-asserted-by":"publisher","DOI":"10.1111\/1467-985X.00091"},{"key":"2025100521493075000_75.1.29.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.infbeh.2011.09.005"},{"key":"2025100521493075000_75.1.29.26","unstructured":"McCarthy D . Manual for the McCarthy Scales of Children\u2019s Abilities . New York: The Psychological Corporation, 1972."},{"key":"2025100521493075000_75.1.29.27","doi-asserted-by":"crossref","unstructured":"Kampouri M , Kyriklaki A , Roumeliotaki T , et al. Patterns of early-life social and environmental exposures and child cognitive development, Rhea birth cohort, Crete, Greece. Child Dev 2017. doi: 10.1111\/cdev.12782","DOI":"10.1111\/cdev.12782"},{"key":"2025100521493075000_75.1.29.28","unstructured":"Raven JC , Court JH , Raven JE . Raven\u2019s Coloured Progressive Matrices . Harcourt Assessment, 1998."},{"key":"2025100521493075000_75.1.29.29","unstructured":"Lezak M , Howieson D , Loring D Neuropsychological assessment. New York: Oxford University Press. Orientation and attention 2004: 351\u201360."},{"key":"2025100521493075000_75.1.29.30","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0274"},{"key":"2025100521493075000_75.1.29.31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316262"},{"key":"2025100521493075000_75.1.29.32","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0457"},{"key":"2025100521493075000_75.1.29.33","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2005.15.44"},{"key":"2025100521493075000_75.1.29.34","doi-asserted-by":"crossref","unstructured":"Moleti M , Trimarchi F , Vermiglio F . Doubts and concerns about isolated maternal hypothyroxinemia. J Thyroid Res 2011;2011. doi: 10.4061\/2011\/463029","DOI":"10.4061\/2011\/463029"},{"key":"2025100521493075000_75.1.29.35","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000262054.03531.24"},{"key":"2025100521493075000_75.1.29.36","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1210\/jc.2017-02378","article-title":"Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child cognition","volume":"103","author":"Hales","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2025100521493075000_75.1.29.37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106104"},{"key":"2025100521493075000_75.1.29.38","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2797"},{"key":"2025100521493075000_75.1.29.39","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.93"},{"key":"2025100521493075000_75.1.29.40","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1007\/s12035-015-9101-x","article-title":"Maternal hypothyroxinemia-induced neurodevelopmental impairments in the progeny","volume":"53","author":"Min","year":"2016","journal-title":"Mol Neurobiol"}],"container-title":["Journal of Epidemiology and Community Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jech-2019-213309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:49:39Z","timestamp":1759726179000},"score":1,"resource":{"primary":{"URL":"https:\/\/jech.bmj.com\/lookup\/doi\/10.1136\/jech-2019-213309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12,10]]},"published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1136\/jech-2019-213309"],"URL":"https:\/\/doi.org\/10.1136\/jech-2019-213309","relation":{},"ISSN":["0143-005X","1470-2738"],"issn-type":[{"value":"0143-005X","type":"print"},{"value":"1470-2738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]}}}