Skip to main content
Top
Published in: Thyroid Research 1/2019

Open Access 01-12-2019 | Miscarriage | Commentary

Levothyroxine before conception in women with thyroid antibodies: a step forward in the management of thyroid disease in pregnancy

Author: Roberto Negro

Published in: Thyroid Research | Issue 1/2019

Login to get access

Abstract

Studies suggesting an association between thyroid autoimmunity and pregnancy-related adverse outcomes, particularly miscarriage and preterm delivery, date to nineties. The postulated causes for these associations were attributed to a direct or indirect effect of autoimmunity and/or to a mild thyroid impairment.
Since then, small trials and several meta-analyses confirmed a detrimental effect of thyroid autoimmunity and suggested that patients with thyroid autoimmunity who wish to conceive or are pregnant might benefit from levothyroxine treatment to decrease the rate of miscarriage and preterm delivery.
A recently published large trial investigated the hypothesis that the administration of levothyroxine in euthyroid antibody-positive women seeking pregnancy might increase the live birth rate.
Women who were trying to conceive and had a history of miscarriage or infertility were tested for TSH and thyroperoxidase antibodies. Euthyroid antibody positive women were randomized to receive 50 μg/day of levothyroxine or placebo and were tested for thyroid function throughout pregnancy. In patients with thyroid function test results outside of assay-specific reference limits, the trial agent was discontinued. 56.6% in the LT4 group and 58.3% in the placebo group became pregnant and the live birth rates were similar in the two groups (37.4% vs 37.9%, respectively). There was also no difference in pre-term delivery rate and other maternal and neonatal outcomes between the two groups.
The present commentary discusses the main findings of the trial and implications for clinical practice.
Literature
1.
go back to reference Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264:1422–5.CrossRef Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264:1422–5.CrossRef
2.
go back to reference Glinoer D, Riahi M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 1994;79:197–204.PubMed Glinoer D, Riahi M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 1994;79:197–204.PubMed
3.
go back to reference Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab. 2011;96:E920–4.CrossRef Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab. 2011;96:E920–4.CrossRef
4.
go back to reference Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab. 2006;91:2587–91.CrossRef Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab. 2006;91:2587–91.CrossRef
5.
go back to reference Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616.CrossRef Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616.CrossRef
6.
go back to reference Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One. 2017;12:e0175708.CrossRef Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One. 2017;12:e0175708.CrossRef
7.
go back to reference Rao M, Zeng Z, Zhou F, Wang H, Liu J, Wang R, Wen Y, Yang Z, Su C, Su Z, Zhao S, Tang L. Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:344–61.CrossRef Rao M, Zeng Z, Zhou F, Wang H, Liu J, Wang R, Wen Y, Yang Z, Su C, Su Z, Zhao S, Tang L. Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:344–61.CrossRef
8.
go back to reference Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, Underwood M, Kilby MD, Boelaert K, Daniels J, Thangaratinam S, Chan SY, Coomarasamy A. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019;380:1316–25.CrossRef Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, Underwood M, Kilby MD, Boelaert K, Daniels J, Thangaratinam S, Chan SY, Coomarasamy A. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019;380:1316–25.CrossRef
9.
go back to reference Wang H, Gao H, Chi H, Zeng L, Xiao W, Wang Y, Li R, Liu P, Wang C, Tian Q, Zhou Z, Yang J, Liu Y, Wei R, Mol BWJ, Hong T, Qiao J. Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer: A Randomized Clinical Trial. JAMA. 2017;318:2190–8.CrossRef Wang H, Gao H, Chi H, Zeng L, Xiao W, Wang Y, Li R, Liu P, Wang C, Tian Q, Zhou Z, Yang J, Liu Y, Wei R, Mol BWJ, Hong T, Qiao J. Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer: A Randomized Clinical Trial. JAMA. 2017;318:2190–8.CrossRef
10.
go back to reference Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, Chiusano E, John R, Guaraldo V, George LM, Perona M, Dall'Amico D, Parkes AB, Joomun M, Wald NJ. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366:493–501.CrossRef Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, Chiusano E, John R, Guaraldo V, George LM, Perona M, Dall'Amico D, Parkes AB, Joomun M, Wald NJ. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366:493–501.CrossRef
11.
go back to reference Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017;376:815–25.CrossRef Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017;376:815–25.CrossRef
12.
go back to reference Negro R, Schwartz A, Stagnaro-Green A. Impact of Levothyroxine in Miscarriage and Preterm Delivery Rates in First Trimester Thyroid Antibody-Positive Women With TSH Less Than 2.5 mIU/L. J Clin Endocrinol Metab. 2016;101(10):3685–90.CrossRef Negro R, Schwartz A, Stagnaro-Green A. Impact of Levothyroxine in Miscarriage and Preterm Delivery Rates in First Trimester Thyroid Antibody-Positive Women With TSH Less Than 2.5 mIU/L. J Clin Endocrinol Metab. 2016;101(10):3685–90.CrossRef
13.
go back to reference Dong AC, Stagnaro-Green A. Differences in Diagnostic Criteria Mask the True Prevalence of Thyroid Disease in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid. 2019;29:278–89.CrossRef Dong AC, Stagnaro-Green A. Differences in Diagnostic Criteria Mask the True Prevalence of Thyroid Disease in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid. 2019;29:278–89.CrossRef
14.
go back to reference Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27:315–89.CrossRef Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27:315–89.CrossRef
15.
go back to reference Taylor PN, Minassian C, Rehman A, Iqbal A, Draman MS, Hamilton W, Dunlop D, Robinson A, Vaidya B, Lazarus JH, Thomas S, Dayan CM, Okosieme OE. TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study. J Clin Endocrinol Metab. 2014;99:3895–902.CrossRef Taylor PN, Minassian C, Rehman A, Iqbal A, Draman MS, Hamilton W, Dunlop D, Robinson A, Vaidya B, Lazarus JH, Thomas S, Dayan CM, Okosieme OE. TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study. J Clin Endocrinol Metab. 2014;99:3895–902.CrossRef
16.
go back to reference Vissenberg R, van Dijk MM, Fliers E, van der Post JAM, van Wely M, Bloemenkamp KWM, Hoek A, Kuchenbecker WK, Verhoeve HR, Scheepers HCJ, Rombout-de Weerd S, Koks C, Zwart JJ, Broekmans F, Verpoest W, Christiansen OB, Post M, Papatsonis DNM, Verberg MFG, Sikkema J, Mol BW, Bisschop PH, Goddijn M. Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study). Contemp Clin Trials. 2015;44:134–8.CrossRef Vissenberg R, van Dijk MM, Fliers E, van der Post JAM, van Wely M, Bloemenkamp KWM, Hoek A, Kuchenbecker WK, Verhoeve HR, Scheepers HCJ, Rombout-de Weerd S, Koks C, Zwart JJ, Broekmans F, Verpoest W, Christiansen OB, Post M, Papatsonis DNM, Verberg MFG, Sikkema J, Mol BW, Bisschop PH, Goddijn M. Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study). Contemp Clin Trials. 2015;44:134–8.CrossRef
17.
go back to reference Laurberg P, Andersen SL, Pedersen IB, Andersen S, Carlé A. Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests. Clin Endocrinol (Oxf). 2013;79:297–304.CrossRef Laurberg P, Andersen SL, Pedersen IB, Andersen S, Carlé A. Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests. Clin Endocrinol (Oxf). 2013;79:297–304.CrossRef
Metadata
Title
Levothyroxine before conception in women with thyroid antibodies: a step forward in the management of thyroid disease in pregnancy
Author
Roberto Negro
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Thyroid Research / Issue 1/2019
Electronic ISSN: 1756-6614
DOI
https://doi.org/10.1186/s13044-019-0066-0

Other articles of this Issue 1/2019

Thyroid Research 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.