{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:24:53Z","timestamp":1791563093704,"version":"4.3.4"},"reference-count":27,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Numerous studies have found that subclinical hypothyroidism (SCH) may increase adverse pregnancy outcomes; however, the benefit of levothyroxine (LT4) treatment remains controversial. The 2017 guidelines of the American Thyroid Association weakly recommended LT4 therapy for serum antithyroid peroxidase antibody (TPOAb)-negative women with thyroid-stimulating hormone (TSH) concentrations greater than the pregnancy-specific reference range and below 10.0 mU\/L. Therefore, the primary goal of this study was to investigate the correlation between thyroid autoantibody-negative SCH with or without LT4 treatment and adverse pregnancy outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We prospectively enrolled 1868 consecutive pregnant women. Finally, 1344 women were involved in the study according to the inclusion and exclusion criteria. Assays for TSH, free thyroxine (FT4), TPOAb, anti-thyroglobulin antibody, and laboratory indicators were performed. The participants were divided into the euthyroid (ET) group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009\u2009=\u20091250) and the SCH group(\n                      <jats:italic>n<\/jats:italic>\n                      \u2009\u2009= 94). The SCH group was further divided into LT4 group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009\u2009=\u200940) and non-LT4 group(\n                      <jats:italic>n<\/jats:italic>\n                      \u2009\u2009= 54). The laboratory indicators and pregnancy outcomes were evaluated during follow-ups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Maternal age, BMI, parity, and the history of spontaneous abortion did not differ significantly between the ET group and the different SCH groups. There were no significant differences in lipid profile and homocysteine levels between ET and SCH group in the first and third trimester of pregnancy. After adjusting the confounding factors, the non-LT4 group was a risk factor for spontaneous abortion (odds ratio: 3.141, 95% CI: 1.060\u20139.302). Survival analysis showed that the time of abortion was different between the ET group and SCH group (log-rank\n                      <jats:italic>P<\/jats:italic>\n                      = 0.042). The spontaneous abortion in SCH, especially in non-LT4, group mainly occurred in the first trimester of pregnancy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thyroid autoantibody negative-SCH seems to be associated with increased risk of spontaneous abortions during the first trimester of pregnancy. LT4 therapy in this patient population might be beneficial to reduce adverse pregnancy outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-21-0600","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:30:20Z","timestamp":1646739020000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":9,"title":["Untreated thyroid autoantibody-negative SCH increases the risk of spontaneous abortions"],"prefix":"10.1530","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9218-1720","authenticated-orcid":true,"given":"Ning","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0510-6352","authenticated-orcid":true,"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Thyroid","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1089\/thy.2016.0457","article-title":"2017 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","unstructured":"Alexander EKPearce ENBrent GABrown RSChen HDosiou CGrobman WALaurberg PLazarus JHMandel SJ2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid201727315\u2013389. (https:\/\/doi.org\/10.1089\/thy.2016.0457)2805669010.1089\/thy.2016.0457"},{"key":"bib2","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.1210\/jc.2011-0274","article-title":"Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China","volume":"96","author":"Su","year":"2011","unstructured":"Su PYHuang KHao JHXu YQYan SQLi TXu YHTao FB. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. Journal of Clinical Endocrinology and Metabolism2011963234\u20133241. (https:\/\/doi.org\/10.1210\/jc.2011-0274)2183211010.1210\/jc.2011-0274"},{"key":"bib3","series-title":"Human Reproduction Update","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1093\/humupd\/dms007","article-title":"Treatment of thyroid disorders before conception and in early pregnancy: a systematic review","volume":"18","author":"Vissenberg","year":"2012","unstructured":"Vissenberg Rvan den Boogaard Evan Wely Mvan der Post JAFliers EBisschop PHGoddijn M. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Human Reproduction Update201218360\u2013373. (https:\/\/doi.org\/10.1093\/humupd\/dms007)2243156510.1093\/humupd\/dms007"},{"key":"bib4","series-title":"Experimental and Therapeutic Medicine","first-page":"1807","article-title":"Effects of thyroid diseases on pregnancy outcomes","volume":"18","author":"Zhou","year":"2019","unstructured":"Zhou MWang MLi JLuo XLei M. Effects of thyroid diseases on pregnancy outcomes. Experimental and Therapeutic Medicine2019181807\u20131815. (https:\/\/doi.org\/10.3892\/etm.2019.7739)31410141"},{"key":"bib5","series-title":"Frontiers in Endocrinology","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3389\/fendo.2019.00522","article-title":"The impact of subclinical hypothyroidism on adverse perinatal outcomes and the role of thyroid screening in pregnancy","volume":"10","author":"Wu","year":"2019","unstructured":"Wu MQLiu JWang YQYang YYan CHHua J. The impact of subclinical hypothyroidism on adverse perinatal outcomes and the role of thyroid screening in pregnancy. Frontiers in Endocrinology201910522. (https:\/\/doi.org\/10.3389\/fendo.2019.00522)3144777810.3389\/fendo.2019.00522"},{"key":"bib6","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"4464","DOI":"10.1210\/jc.2012-2540","article-title":"Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes","volume":"97","author":"Karakosta","year":"2012","unstructured":"Karakosta PAlegakis DGeorgiou VRoumeliotaki TFthenou EVassilaki MBoumpas DCastanas EKogevinas MChatzi L. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. Journal of Clinical Endocrinology and Metabolism2012974464\u20134472. (https:\/\/doi.org\/10.1210\/jc.2012-2540)2301565110.1210\/jc.2012-2540"},{"key":"bib7","series-title":"Thyroid","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1089\/thy.2014.0029","article-title":"Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study","volume":"24","author":"Liu","year":"2014","unstructured":"Liu HShan ZLi CMao JXie XWang WFan CWang HZhang HHan CMaternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid2014241642\u20131649. (https:\/\/doi.org\/10.1089\/thy.2014.0029)2508768810.1089\/thy.2014.0029"},{"key":"bib8","series-title":"Journal of Obstetrics and Gynaecology Research","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1111\/jog.13925","article-title":"Pregnancy outcomes of antibody negative and untreated subclinical hypothyroidism","volume":"45","author":"Cakmak","year":"2019","unstructured":"Cakmak BDTurker UATemur MUstunyurt E. Pregnancy outcomes of antibody negative and untreated subclinical hypothyroidism. Journal of Obstetrics and Gynaecology Research201945810\u2013816. (https:\/\/doi.org\/10.1111\/jog.13925)3067207010.1111\/jog.13925"},{"key":"bib9","series-title":"PLoS ONE","article-title":"Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: a systematic review and meta-analysis","volume":"12","author":"Zhang","year":"2017","unstructured":"Zhang YWang HPan XTeng WShan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: a systematic review and meta-analysis. PLoS ONE201712 e0175708. (https:\/\/doi.org\/10.1371\/journal.pone.0175708)28414788"},{"key":"bib10","series-title":"Bioengineered","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.1080\/21655979.2021.1955589","article-title":"Laboratory characteristics analysis of the efficacy of levothyroxine on subclinical hypothyroidism during pregnancy: a single-center retrospective study","volume":"12","author":"Han","year":"2021","unstructured":"Han LMa YLiang ZChen D. Laboratory characteristics analysis of the efficacy of levothyroxine on subclinical hypothyroidism during pregnancy: a single-center retrospective study. Bioengineered2021124183\u20134190. (https:\/\/doi.org\/10.1080\/21655979.2021.1955589)3428880810.1080\/21655979.2021.1955589"},{"key":"bib11","series-title":"BMC Pregnancy and Childbirth","article-title":"Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study","volume":"20","author":"Yuan","year":"2020","unstructured":"Yuan NSun JLi ZChai SZhang XJi L. Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study. BMC Pregnancy and Childbirth202020 491. (https:\/\/doi.org\/10.1186\/s12884-020-03176-4)32847542"},{"key":"bib12","series-title":"Thyroid","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1089\/thy.2015.0418","article-title":"Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis","volume":"26","author":"Maraka","year":"2016","unstructured":"Maraka SOspina NMO'Keeffe DTEspinosa De Ycaza AEGionfriddo MRErwin PJCoddington CCStan MNMurad MHMontori VM. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid201626580\u2013590. (https:\/\/doi.org\/10.1089\/thy.2015.0418)2683726810.1089\/thy.2015.0418"},{"key":"bib13","series-title":"Endocrine Connections","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1530\/EC-19-0316","article-title":"Maternal TSH levels at first trimester and subsequent spontaneous miscarriage: a nested case-control study","volume":"8","author":"Li","year":"2019","unstructured":"Li JLiu ALiu HLi CWang WHan CWang XZhang YTeng WShan Z. Maternal TSH levels at first trimester and subsequent spontaneous miscarriage: a nested case-control study. Endocrine Connections201981288\u20131293. (https:\/\/doi.org\/10.1530\/EC-19-0316)3152572910.1530\/EC-19-0316"},{"key":"bib14","series-title":"Clinical Endocrinology","first-page":"163","article-title":"Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: a prospective population-based cohort study","volume":"91","author":"Kianpour","year":"2019","unstructured":"Kianpour MAminorroaya AAmini MFeizi AAminorroaya SJanghorbani M. Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: a prospective population-based cohort study. Clinical Endocrinology201991163\u2013169. (https:\/\/doi.org\/10.1111\/cen.13979)30927551"},{"key":"bib15","series-title":"Tohoku Journal of Experimental Medicine","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1620\/tjem.242.167","article-title":"Women with subclinical hypothyroidism are at low risk of poor pregnancy outcome in Japan","volume":"242","author":"Furukawa","year":"2017","unstructured":"Furukawa SMiyakawa KShibata JIwashita M. Women with subclinical hypothyroidism are at low risk of poor pregnancy outcome in Japan. Tohoku Journal of Experimental Medicine2017242167\u2013172. (https:\/\/doi.org\/10.1620\/tjem.242.167)2869028110.1620\/tjem.242.167"},{"key":"bib16","series-title":"Obstetrics and Gynecology","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/AOG.0b013e3181788dd7","article-title":"Maternal thyroid hypofunction and pregnancy outcome","volume":"112","author":"Cleary-Goldman","year":"2008","unstructured":"Cleary-Goldman JMalone FDLambert-Messerlian GSullivan LCanick JPorter TFLuthy DGross SBianchi DWD\u2019Alton ME. Maternal thyroid hypofunction and pregnancy outcome. Obstetrics and Gynecology200811285\u201392. (https:\/\/doi.org\/10.1097\/AOG.0b013e3181788dd7)1859131210.1097\/AOG.0b013e3181788dd7"},{"key":"bib17","series-title":"Thyroid","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1089\/thy.2018.0475","article-title":"Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and meta-analysis","volume":"29","author":"Dong","year":"2019","unstructured":"Dong ACStagnaro-Green A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and meta-analysis. Thyroid201929278\u2013289. (https:\/\/doi.org\/10.1089\/thy.2018.0475)3044418610.1089\/thy.2018.0475"},{"key":"bib18","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1210\/jc.2017-01850","article-title":"Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies","volume":"103","author":"Nazarpour","year":"2018","unstructured":"Nazarpour SRamezani Tehrani FSimbar MTohidi MMinooee SRahmati MAzizi F. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. Journal of Clinical Endocrinology and Metabolism2018103926\u2013935. (https:\/\/doi.org\/10.1210\/jc.2017-01850)2912629010.1210\/jc.2017-01850"},{"key":"bib19","series-title":"Gynecological Endocrinology","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1080\/09513590.2018.1451836","article-title":"Initiation timing effect of levothyroxine treatment on subclinical hypothyroidism in pregnancy","volume":"34","author":"Zhao","year":"2018","unstructured":"Zhao LJiang GTian XZhang XZhu TChen BWang YMa Q. Initiation timing effect of levothyroxine treatment on subclinical hypothyroidism in pregnancy. Gynecological Endocrinology201834845\u2013848. (https:\/\/doi.org\/10.1080\/09513590.2018.1451836)2956076210.1080\/09513590.2018.1451836"},{"key":"bib20","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1210\/jc.2004-0785","article-title":"The in vitro effects of triiodothyronine on epidermal growth factor-induced trophoblast function","volume":"90","author":"Barber","year":"2005","unstructured":"Barber KJFranklyn JAMcCabe CJKhanim FLBulmer JNWhitley GSKilby MD. The in vitro effects of triiodothyronine on epidermal growth factor-induced trophoblast function. Journal of Clinical Endocrinology and Metabolism2005901655\u20131661. (https:\/\/doi.org\/10.1210\/jc.2004-0785)1559869710.1210\/jc.2004-0785"},{"key":"bib21","series-title":"Fertility and Sterility","first-page":"23","article-title":"Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology","volume":"95","year":"2011","unstructured":"Aghajanova LStavreus-Evers ALindeberg MLandgren BMSparre LS & Hovatta O. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertility and Sterility201195230\u2013237, 237.e1\u2013237.e2. (https:\/\/doi.org\/10.1016\/j.fertnstert.2010.06.079)"},{"key":"bib22","series-title":"FASEB Journal","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1096\/fj.07-8652com","article-title":"Control of dendritic cell maturation and function by triiodothyronine","volume":"22","author":"Mascanfroni","year":"2008","unstructured":"Mascanfroni IMontesinos Mdel MSusperreguy SCervi LIlarregui JMRamseyer VDMasini-Repiso AMTargovnik HMRabinovich GAPellizas CG. Control of dendritic cell maturation and function by triiodothyronine. FASEB Journal2008221032\u20131042. (https:\/\/doi.org\/10.1096\/fj.07-8652com)1799173210.1096\/fj.07-8652com"},{"key":"bib23","series-title":"International Journal of Gynaecology and Obstetrics","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/ijgo.12751","article-title":"Meta-analysis of the association between maternal subclinical hypothyroidism and gestational diabetes mellitus","volume":"144","author":"Jia","year":"2019","unstructured":"Jia MWu YLin BShi YZhang QLin YWang SZhang Y. Meta-analysis of the association between maternal subclinical hypothyroidism and gestational diabetes mellitus. International Journal of Gynaecology and Obstetrics2019144239\u2013247. (https:\/\/doi.org\/10.1002\/ijgo.12751)3057866910.1002\/ijgo.12751"},{"key":"bib24","series-title":"PLoS ONE","article-title":"Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population","volume":"9","author":"Chen","year":"2014","unstructured":"Chen LMDu WJDai JZhang QSi GXYang HYe ELChen QSYu LCZhang CEffects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. PLoS ONE20149 e109364. (https:\/\/doi.org\/10.1371\/journal.pone.0109364)25353960"},{"key":"bib25","series-title":"Scientific Reports","article-title":"Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes","volume":"11","author":"Li","year":"2021","unstructured":"Li JXu YSun ZCai YWang BZhang MBan YHou XHao YOuyang QDifferential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes. Scientific Reports202111 19689. (https:\/\/doi.org\/10.1038\/s41598-021-99252-6)"},{"key":"bib26","series-title":"Scientific Reports","article-title":"Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population","volume":"10","author":"Zhang","year":"2020","unstructured":"Zhang TXia YHan TLZhang HBaker PN. Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population. Scientific Reports202010 6743. (https:\/\/doi.org\/10.1038\/s41598-020-63513-7)"},{"key":"bib27","series-title":"Hormone and Metabolic Research","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1055\/a-1199-2633","article-title":"Association between plasma homocysteine levels and subclinical hypothyroidism in adult subjects: a meta-analysis","volume":"52","author":"Zhang","year":"2020","unstructured":"Zhang SFLi LZZhang WGuo JRLiu FFMa KChen SHZhang YQ. Association between plasma homocysteine levels and subclinical hypothyroidism in adult subjects: a meta-analysis. Hormone and Metabolic Research202052625\u2013638. (https:\/\/doi.org\/10.1055\/a-1199-2633)3262951910.1055\/a-1199-2633"}],"container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/11\/4\/EC-21-0600.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/11\/4\/EC-21-0600.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/11\/4\/EC-21-0600.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:45:12Z","timestamp":1784555112000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,1]]},"references-count":27,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/ec-21-0600","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,1]]}}}