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Levothyroxine in women with thyroid peroxidase antibodies before conception

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

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Rima K. Dhillon-Smith

Lee J. Middleton

Kirandeep K. Sunner

Versha Cheed

Krys Baker

Samantha Farrell-Carver

Ruth Bender-Atik

Rina Agrawal

Kalsang Bhatia

Edmond Edi-Osagie

Tarek Ghobara

Pratima Gupta

Davor Jurkovic

Yacoub Khalaf

Marjory MacLean

Christopher McCabe

Khashia Mulbagal

Natalie Nunes

Caroline Overton

Siobhan Quenby

Raj Rai

Clinical Associate Professor & Reader in Reproductive Medicine and Surgery

Lynne Robinson

Jackie Ross

Andrew Sizer

Rachel Small

Alex Tan

Martyn Underwood

Mark D. Kilby

Kristien Boelaert

Shakila Thangaratinam

Shiao Y. Chan

Arri Coomarasamy


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.

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.

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).

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.)


Dhillon-Smith, R. K., Middleton, L. J., Sunner, K. K., Cheed, V., Baker, K., Farrell-Carver, S., …Coomarasamy, A. (2019). Levothyroxine in women with thyroid peroxidase antibodies before conception. New England Journal of Medicine, 380(14), 1316-1325.

Journal Article Type Article
Acceptance Date Feb 5, 2019
Publication Date Apr 4, 2019
Deposit Date Apr 5, 2019
Publicly Available Date Oct 5, 2019
Journal New England Journal of Medicine
Print ISSN 0028-4793
Electronic ISSN 1533-4406
Publisher Massachusetts Medical Society
Peer Reviewed Peer Reviewed
Volume 380
Issue 14
Pages 1316-1325
Keywords General medicine
Public URL
Publisher URL
Additional Information From Rima K. Dhillon-Smith, M.B., Ch.B., Ph.D., Lee J. Middleton, M.Sc., Kirandeep K. Sunner, M.Sc., Versha Cheed, M.Sc., Krys Baker, Samantha Farrell-Carver, Ruth Bender-Atik, B.A., Rina Agrawal, M.B., B.S., Ph.D., Kalsang Bhatia, M.B., B.S., Edmond Edi-Osagie, M.B., B.S., M.D., Tarek Ghobara, M.B., Ch.B., Pratima Gupta, M.D., Davor Jurkovic, M.D., Ph.D.,
Yacoub Khalaf, M.B., Ch.B., M.D., Marjory MacLean, M.B., Ch.B., M.D., Christopher McCabe, Ph.D., Khashia Mulbagal, M.B., B.S., Natalie Nunes, M.B., B.S., M.D., Caroline Overton, M.D., Siobhan Quenby, M.D., Raj Rai, M.D., Nick Raine-Fenning, M.B., Ch.B., Ph.D.,
Lynne Robinson, M.B., Ch.B., M.D., Jackie Ross, M.B., B.S., Andrew Sizer, M.D., Ph.D., Rachel Small, B.Sc., F.R.C.O.G., Alex Tan, M.B., Ch.B., Martyn Underwood, M.B., Ch.B., Mark D. Kilby, D.Sc., M.D., Kristien Boelaert, M.D., Ph.D., Jane Daniels, Ph.D., Shakila Thangaratinam, Ph.D., Shiao Y. Chan, M.B., Ch.B., Ph.D., and Arri Coomarasamy, M.B., Ch.B., M.D. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception N Engl J Med 2019; 380:1316-1325
DOI: 10.1056/NEJMoa1812537 KJB 08.04.2019

Copyright © (notice year) Massachusetts Medical Society. Reprinted with permission.


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