备孕妇女甲状腺过氧化物酶抗体阳性时应用左甲状腺素
Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.
机构信息
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.).
出版信息
N Engl J Med. 2019 Apr 4;380(14):1316-1325. doi: 10.1056/NEJMoa1812537. Epub 2019 Mar 23.
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.).
背景
甲状腺过氧化物酶抗体与流产和早产风险增加相关，即使甲状腺功能正常也是如此。小型试验表明，使用左甲状腺素可能会降低此类不良结局的发生率。
方法
我们进行了一项双盲、安慰剂对照试验，以研究左甲状腺素治疗是否会增加甲状腺过氧化物酶抗体阳性且有流产或不孕病史的甲状腺功能正常的女性的活产率。来自英国 49 家医院的 19585 名女性接受了甲状腺过氧化物酶抗体和甲状腺功能检测。我们随机分配 952 名女性在受孕前至整个孕期每天服用 50μg 左甲状腺素（476 名女性）或安慰剂（476 名女性）。主要结局是至少 34 周妊娠后的活产。
结果
主要结局的随访率为 98.7%（952 名女性中的 940 名）。左甲状腺素组 470 名女性中有 266 名（56.6%）和安慰剂组 470 名女性中有 274 名（58.3%）受孕。左甲状腺素组的活产率为 37.4%（470 名女性中的 176 名），安慰剂组为 37.9%（470 名女性中的 178 名）（相对风险，0.97；95%置信区间[CI]，0.83 至 1.14，P=0.74；绝对差异，-0.4 个百分点；95%CI，-6.6 至 5.8）。两组间其他妊娠结局（包括妊娠丢失或早产）或新生儿结局无显著差异。左甲状腺素组有 5.9%的女性和安慰剂组有 3.8%的女性发生严重不良事件（P=0.14）。
结论
在甲状腺过氧化物酶抗体阳性的甲状腺功能正常的女性中使用左甲状腺素并未导致活产率高于安慰剂。（由英国国家卫生研究院资助；TABLET 当前对照试验编号，ISRCTN80747730。）
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