{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:09:10Z","timestamp":1780571350641,"version":"3.54.1"},"reference-count":36,"publisher":"The Endocrine Society","issue":"2","funder":[{"DOI":"10.13039\/501100001826","name":"The Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["90700412"],"award-info":[{"award-number":["90700412"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate a dose dependency of thyroperoxidase antibody (TPOAb) concentrations in relation to thyroid function and premature delivery and define a population-based, pregnancy-specific, functional cutoff for TPOAb positivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Population-based studies in the Netherlands (2002 to 2014).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>A total of 11,212 pregnant women (&amp;lt;20 weeks\u2019 gestation).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Thyrotropin (TSH) and FT4 concentrations, premature delivery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, as well as a dose-dependent negative association with FT4 concentrations during early pregnancy (all P &amp;lt; 0.0001). There was a dose-dependent association of TPOAb concentrations with the risk of premature delivery, which was also modified by TSH concentrations. Women with TPOAb concentrations from the 92nd percentile upward had a higher TSH and a higher risk of a TSH &amp;gt;2.5 mU\/L (range, 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cutoffs already had a higher risk of premature delivery, especially when TSH concentrations were high or in the high-normal range.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrated a dose-dependent relationship between TPOAbs and thyroid function as well as the risk of premature delivery. Furthermore, our results indicate that the currently used cutoffs for TPOAb positivity may be too high. Furthermore, the use of a population-based cutoff for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk of premature delivery but that would not be considered TPOAb positive or eligible for treatment otherwise.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2017-01560","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T20:50:15Z","timestamp":1513111815000},"page":"778-789","source":"Crossref","is-referenced-by-count":58,"title":["Dose Dependency and a Functional Cutoff for TPO-Antibody Positivity During Pregnancy"],"prefix":"10.1210","volume":"103","author":[{"given":"Tim I M","family":"Korevaar","sequence":"first","affiliation":[{"name":"The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor J","family":"Pop","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariette","family":"Goddijn","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda B","family":"de Rijke","sequence":"additional","affiliation":[{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"},{"name":"Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H","family":"Bisschop","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten A","family":"Broeren","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Haematology, M\u00e1xima Medical Centre, Veldhoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent W V","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"},{"name":"Department of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo J","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A P","family":"Steegers","sequence":"additional","affiliation":[{"name":"Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"},{"name":"Department of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja G","family":"Vrijkotte","sequence":"additional","affiliation":[{"name":"Department of Public Health, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin P","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Sophia Children\u2019s Hospital, Rotterdam, the 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Statistical Analysis of Epidemiologic Data. New York, NY: Oxford University Press; 1996: pp. 213\u2013214."},{"key":"2020071623205355700_B28","doi-asserted-by":"crossref","first-page":"b2393","DOI":"10.1136\/bmj.b2393","article-title":"Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls","volume":"338","author":"Sterne","year":"2009","journal-title":"BMJ"},{"key":"2020071623205355700_B29","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.d2616","article-title":"Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence","volume-title":"BMJ","author":"Thangaratinam","year":"2011"},{"issue":"4","key":"2020071623205355700_B30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1530\/EJE-12-0379","article-title":"Thyroid antibodies and risk of preterm delivery: a meta-analysis of prospective cohort studies","volume":"167","author":"He","year":"2012","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"2020071623205355700_B31","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1097\/AOG.0000000000001670","article-title":"An invitation to join the consortium on thyroid and pregnancy","volume":"128","author":"Korevaar","year":"2016","journal-title":"Obstet Gynecol"},{"key":"2020071623205355700_B32","unstructured":"Spencer\n              CA\n            \n          . Assay of thyroid hormones and related substances. [Updated 2017 February 20]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2000-. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279113\/. Accessed 11 July 2017."},{"issue":"2","key":"2020071623205355700_B33","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1210\/jcem-71-2-276","article-title":"Regulation of maternal thyroid during pregnancy","volume":"71","author":"Glinoer","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2020071623205355700_B34","first-page":"69","article-title":"Thyroid autoimmunity impairs the thyroidal response to hCG: two population-based prospective cohort studies","volume":"102","author":"Korevaar","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2020071623205355700_B35","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1210\/jc.2012-4223","article-title":"The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex","volume":"98","author":"Hadlow","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2020071623205355700_B36","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1210\/jc.2014-3704","article-title":"Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China","volume":"100","author":"Shi","year":"2015","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/103\/2\/778\/23792203\/jc.2017-01560.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/103\/2\/778\/23792203\/jc.2017-01560.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T12:12:19Z","timestamp":1594987939000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/103\/2\/778\/4731739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2017-01560","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,2]]},"published":{"date-parts":[[2017,12,12]]}}}