{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:37:37Z","timestamp":1793299057034,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100015537","name":"Department of Pathology and Laboratory Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015537","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dartmouth Hitchcock Health System"},{"name":"Pathology Shared Resource"},{"DOI":"10.13039\/100009230","name":"Norris Cotton Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI Cancer Center Support","award":["5P30 CA023108-37"],"award-info":[{"award-number":["5P30 CA023108-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas\u00ae platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer\u2019s reference interval.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvab009","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T03:27:31Z","timestamp":1610508451000},"page":"772-780","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays"],"prefix":"10.1093","volume":"67","author":[{"given":"K Aaron","family":"Geno","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Health System, Lebanon, NH, USA"},{"name":"Geisel School of Medicine at Dartmouth, Hanover, NH, USA"},{"name":"Department of Pathology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Health System, Lebanon, NH, USA"},{"name":"Southern New Hampshire University, Manchester, NH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Cervinski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Health System, Lebanon, NH, USA"},{"name":"Geisel School of Medicine at Dartmouth, Hanover, NH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D","family":"Nerenz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Health System, Lebanon, NH, USA"},{"name":"Geisel School of Medicine at Dartmouth, Hanover, NH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"2021043007563310100_hvab009-B1","volume-title":"Tietz Textbook of Clinical Chemistry and Molecular Diagnostics","author":"Rifai","edition":"6th ed"},{"key":"2021043007563310100_hvab009-B2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1210\/er.2009-0041","article-title":"Thyroid function and human reproductive health","volume":"31","author":"Krassas","year":"2010","journal-title":"Endocr Rev"},{"key":"2021043007563310100_hvab009-B3","doi-asserted-by":"crossref","first-page":"101431","DOI":"10.1016\/j.beem.2020.101431","article-title":"Interpretation of thyroid function tests during pregnancy","volume":"34","author":"Visser","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2021043007563310100_hvab009-B4","doi-asserted-by":"crossref","first-page":"260.e1","DOI":"10.1016\/j.ajog.2008.10.042","article-title":"Free T4 immunoassays are flawed during pregnancy","volume":"200","author":"Lee","year":"2009","journal-title":"Am J Obstet Gynecol"},{"key":"2021043007563310100_hvab009-B5","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/thy.2016.0457","article-title":"Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum","volume":"27","author":"Alexander","year":"2017","journal-title":"Thyroid"},{"key":"2021043007563310100_hvab009-B6","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1210\/jc.2011-2803","article-title":"Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline","volume":"97","author":"De Groot","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2021043007563310100_hvab009-B7","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.beem.2013.05.012","article-title":"Determination of free thyroid hormones","volume":"27","author":"Thienpont","year":"2013","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2021043007563310100_hvab009-B8","year":"2019"},{"key":"2021043007563310100_hvab009-B9","year":"2019"},{"key":"2021043007563310100_hvab009-B10","year":"2019"},{"key":"2021043007563310100_hvab009-B11","year":"2018"},{"key":"2021043007563310100_hvab009-B12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cccn.2005.02.010","article-title":"The measurement of free thyroxine by isotope dilution tandem mass spectrometry","volume":"358","author":"Soldin","year":"2005","journal-title":"Clin Chim Acta"},{"key":"2021043007563310100_hvab009-B13","year":"2019"},{"key":"2021043007563310100_hvab009-B14","author":"Finnegan","year":"2020"},{"key":"2021043007563310100_hvab009-B15","doi-asserted-by":"crossref","DOI":"10.1016\/0009-8981(87)90151-3","article-title":"Approved recommendation (1987) on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits","volume":"170","author":"Solberg","year":"1987","journal-title":"Clin Chim Acta"},{"key":"2021043007563310100_hvab009-B16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1373\/clinchem.2017.281261","article-title":"Evaluation of thyroid function during pregnancy: have we taken a wrong turn?","volume":"64","author":"Gronowski","year":"2018","journal-title":"Clin Chem"},{"key":"2021043007563310100_hvab009-B17","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/clinchem\/35.9.1891","article-title":"Low-normal concentrations of free thyroxin in serum in late pregnancy: physiological fact, not technical artefact","volume":"35","author":"Ball","year":"1989","journal-title":"Clin Chem"},{"key":"2021043007563310100_hvab009-B18","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1093\/clinchem\/45.12.2250","article-title":"Thyroid function during pregnancy","volume":"45","author":"Fantz","year":"1999","journal-title":"Clin Chem"},{"key":"2021043007563310100_hvab009-B19","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1373\/clinchem.2007.098293","article-title":"Free thyroid hormones in serum by direct equilibrium dialysis and online solid-phase extraction\u2013liquid chromatography\/tandem mass spectrometry","volume":"54","author":"Yue","year":"2008","journal-title":"Clin Chem"},{"key":"2021043007563310100_hvab009-B20","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1089\/thy.2006.0303","article-title":"Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy","volume":"17","author":"Kahric-Janicic","year":"2007","journal-title":"Thyroid"},{"key":"2021043007563310100_hvab009-B21","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/clinchem\/38.5.720","article-title":"Comparison of methods for measuring free thyroxin in nonthyroidal illness","volume":"38","author":"Wong","year":"1992","journal-title":"Clin Chem"},{"key":"2021043007563310100_hvab009-B22"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/5\/772\/37582581\/hvab009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/5\/772\/37582581\/hvab009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T07:58:31Z","timestamp":1619769511000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/67\/5\/772\/6130704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,8]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,2,8]]},"published-print":{"date-parts":[[2021,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvab009","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2021,2,8]]}}}