Levothyroxine in women with thyroid peroxidase antibodies before conception

Rima Smith; Lee Middleton; Kirandeep Sunner; Versha Cheed; Krystyna Baker; Samantha  Farrell-Carver; Ruth Bender Atik; Rina  Agrawal; Kalsang  Bhatia; Edmond  Edi-Osagie; Tarek  Ghobara; Pratima Gupta; Davor  Jurkovic; Yakoub Khalaf; Marjory MacLean; Christopher McCabe; Khashia  Mulbagal; Natalie  Nunes; Caroline  Overton; Siobhan Quenby; Raj Rai; Nick Raine-Fenning; Lynne Robinson; Jackie Ross; Andrew  Sizer; Rachel Small; Alex Tan; Martyn  Underwood; Mark Kilby; Kristien Boelaert; Jane Daniels; Shakila Thangaratinam; Shiao Y Chan; Arri Coomarasamy

doi:10.1056/NEJMoa1812537

Levothyroxine in women with thyroid peroxidase antibodies before conception

Rima Smith, Lee Middleton, Kirandeep Sunner, Versha Cheed, Krystyna Baker, Samantha Farrell-Carver, Ruth Bender Atik, Rina Agrawal, Kalsang Bhatia, Edmond Edi-Osagie, Tarek Ghobara, Pratima Gupta, Davor Jurkovic, Yakoub Khalaf, Marjory MacLean, Christopher McCabe, Khashia Mulbagal, Natalie Nunes, Caroline Overton, Siobhan QuenbyRaj Rai, Nick Raine-Fenning, Lynne Robinson, Jackie Ross, Andrew Sizer, Rachel Small, Alex Tan, Martyn Underwood, Mark Kilby, Kristien Boelaert, Jane Daniels, Shakila Thangaratinam, Shiao Y Chan, Arri Coomarasamy

Research output: Contribution to journal › Article › peer-review

73 Citations (Scopus)

442 Downloads (Pure)

Abstract

BACKGROUND
Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.

METHODS
We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.

RESULTS
The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).

CONCLUSIONS
The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.)

Original language	English
Pages (from-to)	1316-1325
Number of pages	10
Journal	The New England Journal of Medicine
Volume	380
Issue number	14
Early online date	23 Mar 2019
DOIs	https://doi.org/10.1056/NEJMoa1812537
Publication status	Published - 4 Apr 2019

ASJC Scopus subject areas

Medicine(all)

Access to Document

10.1056/NEJMoa1812537Licence: None: All rights reserved

Dhillon-Smith_et_al_Levothyroxine_in_women_with_thyroid_The_New_England_Journal_of_Medicine_2019
Checked for eligibility: 05/04/2019 Initial publication in The New England Journal of Medicine. DOI: 10.1056/NEJMoa1812537
Final published version, 275 KBLicence: None: All rights reserved

Cite this

Smith, R., Middleton, L., Sunner, K., 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., ... Coomarasamy, A. (2019). Levothyroxine in women with thyroid peroxidase antibodies before conception. The New England Journal of Medicine, 380(14), 1316-1325. Advance online publication. https://doi.org/10.1056/NEJMoa1812537

@article{d2c456c6edc94012a5ab07cb927b1f6c,

title = "Levothyroxine in women with thyroid peroxidase antibodies before conception",

abstract = "BACKGROUNDThyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.METHODSWe conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.RESULTSThe follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).CONCLUSIONSThe use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.)",

author = "Rima Smith and Lee Middleton and Kirandeep Sunner and Versha Cheed and Krystyna Baker and Samantha Farrell-Carver and {Bender Atik}, Ruth and Rina Agrawal and Kalsang Bhatia and Edmond Edi-Osagie and Tarek Ghobara and Pratima Gupta and Davor Jurkovic and Yakoub Khalaf and Marjory MacLean and Christopher McCabe and Khashia Mulbagal and Natalie Nunes and Caroline Overton and Siobhan Quenby and Raj Rai and Nick Raine-Fenning and Lynne Robinson and Jackie Ross and Andrew Sizer and Rachel Small and Alex Tan and Martyn Underwood and Mark Kilby and Kristien Boelaert and Jane Daniels and Shakila Thangaratinam and Chan, {Shiao Y} and Arri Coomarasamy",

year = "2019",

month = apr,

day = "4",

doi = "10.1056/NEJMoa1812537",

language = "English",

volume = "380",

pages = "1316--1325",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "14",

}

Smith, R , Middleton, L, Sunner, K, 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, M , Boelaert, K, Daniels, J, Thangaratinam, S, Chan, SY & Coomarasamy, A 2019, 'Levothyroxine in women with thyroid peroxidase antibodies before conception', The New England Journal of Medicine, vol. 380, no. 14, pp. 1316-1325. https://doi.org/10.1056/NEJMoa1812537

TY - JOUR

T1 - Levothyroxine in women with thyroid peroxidase antibodies before conception

AU - Smith, Rima

AU - Middleton, Lee

AU - Sunner, Kirandeep

AU - Cheed, Versha

AU - Baker, Krystyna

AU - Farrell-Carver, Samantha

AU - Bender Atik, Ruth

AU - Agrawal, Rina

AU - Bhatia, Kalsang

AU - Edi-Osagie, Edmond

AU - Ghobara, Tarek

AU - Gupta, Pratima

AU - Jurkovic, Davor

AU - Khalaf, Yakoub

AU - MacLean, Marjory

AU - McCabe, Christopher

AU - Mulbagal, Khashia

AU - Nunes, Natalie

AU - Overton, Caroline

AU - Quenby, Siobhan

AU - Rai, Raj

AU - Raine-Fenning, Nick

AU - Robinson, Lynne

AU - Ross, Jackie

AU - Sizer, Andrew

AU - Small, Rachel

AU - Tan, Alex

AU - Underwood, Martyn

AU - Kilby, Mark

AU - Boelaert, Kristien

AU - Daniels, Jane

AU - Thangaratinam, Shakila

AU - Chan, Shiao Y

AU - Coomarasamy, Arri

PY - 2019/4/4

Y1 - 2019/4/4

N2 - BACKGROUNDThyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.METHODSWe conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.RESULTSThe follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).CONCLUSIONSThe use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.)

AB - BACKGROUNDThyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.METHODSWe conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.RESULTSThe follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).CONCLUSIONSThe use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.)

UR - http://www.scopus.com/inward/record.url?scp=85063949948&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1812537

DO - 10.1056/NEJMoa1812537

M3 - Article

SN - 0028-4793

VL - 380

SP - 1316

EP - 1325

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 14

ER -

Levothyroxine in women with thyroid peroxidase antibodies before conception

Abstract

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this