Levothyroxine in women with thyroid peroxidase antibodies before conception

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 QuenbyRaj Rai, Nick Raine-Fenning, Lynne Robinson, Jackie Ross, Andrew Sizer, Rachel Small, Alex Tan, Martyn Underwood, Mark D. Kilby, Kristien Boelaert, Jane Daniels, Shakila Thangaratinam, Shiao Y. Chan, Arri Coomarasamy*

*Corresponding author for this work

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    182 Citations (Scopus)
    258 Downloads (Pure)


    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.

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


    Dive into the research topics of 'Levothyroxine in women with thyroid peroxidase antibodies before conception'. Together they form a unique fingerprint.

    Cite this