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

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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.)
Original languageEnglish
Pages (from-to)1316-1325
Number of pages10
JournalThe New England Journal of Medicine
Issue number14
Early online date23 Mar 2019
Publication statusPublished - 4 Apr 2019

ASJC Scopus subject areas

  • Medicine(all)


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