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N Engl J Med. 2019 Apr 4;380(14):1316-1325. doi: 10.1056/NEJMoa1812537. Epub 2019 Mar 23.

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.

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From the Institute of Metabolism and Systems Research (R.K.D.-S., C.M., M.D.K., K. Boelaert, A.C.), Tommy's National Centre for Miscarriage Research (R.K.D.-S., A.C.), and the Birmingham Clinical Trials Unit, Institute of Applied Health Research (L.J.M., K.K.S., V.C., S.F.-C.), College of Medical and Dental Sciences, University of Birmingham, the Birmingham Women's and Children's NHS Foundation Trust (R.K.D.-S., L.R., M.D.K., A.C.), and University Hospital Birmingham (P.G., R.S.), Birmingham, the Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford (K. Baker), the Miscarriage Association, Wakefield (R.B.-A.), University Hospital Coventry, University Hospitals Coventry and Warwickshire NHS Trust, Coventry (R.A., T.G., S.Q.), Burnley General Teaching Hospital, East Lancashire Hospitals NHS Trust, Lancashire (K. Bhatia), St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (E.E.-O.), University College Hospital, University College London Hospitals NHS Foundation Trust (D.J.), the Assisted Conception Unit, Guy's and St. Thomas' NHS Foundation Trust (Y.K.), St. Mary's Hospital, Imperial College Healthcare NHS Trust (R.R.), King's College Hospital NHS Foundation Trust (J.R.), and the Barts Research Centre for Women's Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (A.T., S.T.), London, Ayrshire Maternity Unit, University Hospital Crosshouse, Kilmarnock (M.M.), Royal Bolton Hospital, Bolton NHS Foundation Trust, Bolton (K.M.), West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, Chelsea (N.N.), St. Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol (C.O.), Queens Medical Centre, Nottingham University Hospitals NHS Trust (N.R.-F.), and the Nottingham Clinical Trials Unit, University of Nottingham, School of Medicine, Nottingham Health Sciences Partners, Queen's Medical Centre (J.D.), Nottingham, and the Princess Royal Hospital, Shrewsbury and Telford Hospital NHS Trust, Shrewsbury (A.S., M.U.) - all in the United Kingdom; and the Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (S.Y.C.).



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.).

[Indexed for MEDLINE]

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