{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:28:50Z","timestamp":1792290530787,"version":"4.4.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Subclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2021.797423","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T04:33:09Z","timestamp":1639110789000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Pregnancy and Neonatal Outcomes With Levothyroxine Treatment in Women With Subclinical Hypothyroidism Based on New Diagnostic Criteria: A Systematic Review and Meta-Analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Zheng","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yindi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridoula","family":"Maraka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Abdelouahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Feng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxia","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.15537\/smj.2018.3.21621","article-title":"Prevalence of Subclinical Hypothyroidism in Pregnancy in Saudi Arabia","volume":"39","author":"AlShanqeeti","year":"2018","journal-title":"Saudi Med J"},{"key":"B2","doi-asserted-by":"publisher","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","journal-title":"Thyroid"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3275\/7772","article-title":"Effects of Maternal Subclinical Hypothyroidism on Obstetrical Outcomes During Early Pregnancy","volume":"35","author":"Wang","year":"2012","journal-title":"J Endocrinol Invest"},{"key":"B4","doi-asserted-by":"publisher","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","journal-title":"Thyroid"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2855","article-title":"Hypothyroxinemia and TPO-Antibody Positivity Are Risk Factors for Premature Delivery: The Generation R Study","volume":"98","author":"Korevaar","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318240de6a","article-title":"Subclinical Thyroid Disease and the Incidence of Hypertension in Pregnancy","volume":"119","author":"Wilson","year":"2012","journal-title":"Obstet Gynecol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318250aeeb","article-title":"Relationship of Subclinical Thyroid Disease to the Incidence of Gestational Diabetes","volume":"119","author":"Tudela","year":"2012","journal-title":"Obstet Gynecol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e109364","DOI":"10.1371\/journal.pone.0109364","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","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000343759","article-title":"Reduction of Miscarriages Through Universal Screening and Treatment of Thyroid Autoimmune Diseases","volume":"74","author":"Lepoutre","year":"2012","journal-title":"Gynecol Obstet Invest"},{"key":"B10","doi-asserted-by":"publisher","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","journal-title":"J Clin Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0014","article-title":"Effects of Levothyroxine Therapy on Pregnancy Outcomes in Women With Subclinical Hypothyroidism","volume":"26","author":"Maraka","year":"2016","journal-title":"Thyroid"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1803","article-title":"Impact of Levothyroxine in Miscarriage and Preterm Delivery Rates in First Trimester Thyroid Antibody-Positive Women With TSH Less Than 2.5 mIU\/L","volume":"101","author":"Negro","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz217","article-title":"A Meta-Analysis of Pregnancy Outcomes With Levothyroxine Treatment in Euthyroid Women With Thyroid Autoimmunity","volume":"105","author":"Sun","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","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":"B15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1159\/000362597","article-title":"European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children","volume":"3","author":"Lazarus","year":"2014","journal-title":"Eur Thyroid J"},{"key":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-019-05245-2","article-title":"Levothyroxine Treatment and Pregnancy Outcomes in Women With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis","volume":"300","author":"Nazarpour","year":"2019","journal-title":"Arch Gynecol Obstet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000051","article-title":"Thyroid Function Reference Ranges During Pregnancy in a Large Chinese Population and Comparison With Current Guidelines","volume":"132","author":"Yang","year":"2019","journal-title":"Chin Med J (Engl)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005","article-title":"Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement","volume":"62","author":"Moher","year":"2009","journal-title":"J Clin Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical Evaluation of the Newcastle-Ottawa Scale for the Assessment of the Quality of Nonrandomized Studies in Meta-Analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0197-2456(95)00134-4","article-title":"Assessing the Quality of Reports of Randomized Clinical Trials: Is Blinding Necessary","volume":"17","author":"Jadad","year":"1996","journal-title":"Controlled Clin Trials"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s Tool for Assessing Risk of Bias in Randomised Trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606205","article-title":"Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy","volume":"376","author":"Casey","year":"2017","journal-title":"N Engl J Med"},{"key":"B24","article-title":"Clinical Observation of L-T4 Treatment in Subclinical Hypothyroidism in Pregnancy With Autoantibody Negative","volume":"28","author":"Ye","year":"2019","journal-title":"Prog Obstet Gynecol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6865","article-title":"Thyroid Hormone Treatment Among Pregnant Women With Subclinical Hypothyroidism: US National Assessment","volume":"356","author":"Maraka","year":"2017","journal-title":"BMJ"},{"key":"B26","article-title":"Effect of the Treatment Acceptance on the Perinatal Outcomes in Women With Subclinical Hypothyroidism, Positive Thyroid Gland Peroxidase Antibody in Early Pregnancy","volume":"50","author":"Yang","year":"2015","journal-title":"Chin J Obstet Gynecol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0548","article-title":"Effects of Levothyroxine Treatment on Pregnancy Outcomes in Pregnant Women With Autoimmune Thyroid Disease","volume":"176","author":"Nazarpour","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812537","article-title":"Levothyroxine in Women With Thyroid Peroxidase Antibodies Before Conception","volume":"380","author":"Dhillon-Smith","year":"2019","journal-title":"N Engl J Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0087","article-title":"Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum","volume":"21","author":"Stagnaro-Green","year":"2011","journal-title":"Thyroid"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0418","article-title":"Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis","volume":"26","author":"Maraka","year":"2016","journal-title":"Thyroid"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.797423\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T04:33:13Z","timestamp":1639110793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.797423\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":30,"alternative-id":["10.3389\/fendo.2021.797423"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.797423","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]},"article-number":"797423"}}