Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception

被引：191

作者：

Dhillon-Smith, Rima K. ^{[1
,2
,4
]}

Middleton, Lee J. ^{[3
,4
]}

Sunner, Kirandeep K. ^{[3
]}

Cheed, Versha ^{[3
]}

Baker, Krys ^{[6
]}

Farrell-Carver, Samantha ^{[3
]}

Bender-Atik, Ruth ^{[7
]}

Agrawal, Rina ^{[8
]}

Bhatia, Kalsang ^{[9
]}

Edi-Osagie, Edmond ^{[10
]}

Ghobara, Tarek ^{[8
]}

Gupta, Pratima ^{[5
]}

Jurkovic, Davor ^{[11
]}

Khalaf, Yacoub ^{[12
]}

MacLean, Marjory ^{[16
]}

McCabe, Christopher ^{[1
]}

Mulbagal, Khashia ^{[17
]}

Nunes, Natalie ^{[18
]}

Overton, Caroline ^{[19
]}

Quenby, Siobhan ^{[8
]}

Rai, Raj ^{[13
]}

Raine-Fenning, Nick ^{[20
]}

Robinson, Lynne ^{[3
,4
]}

Ross, Jackie ^{[14
]}

Sizer, Andrew ^{[22
]}

Small, Rachel ^{[5
]}

Tan, Alex ^{[15
]}

Underwood, Martyn ^{[22
]}

Kilby, Mark D. ^{[1
,4
]}

Boelaert, Kristien ^{[1
]}

Daniels, Jane ^{[21
]}

Thangaratinam, Shakila ^{[15
]}

Chan, Shiao Y. ^{[23
]}

Coomarasamy, Arri ^{[1
,2
,4
]}

机构：

[1] Univ Birmingham, Coll Med & Dent Sci, Inst Metab & Syst Res, Birmingham B15 2TT, W Midlands, England

[2] Univ Birmingham, Coll Med & Dent Sci, Tommys Natl Ctr Miscarriage Res, Birmingham E15 2TT, W Midlands, England

[3] Univ Birmingham, Coll Med & Dent Sci, Birmingham Clin Trials Unit, Inst Appl Hlth Res, Birmingham, W Midlands, England

[4] Univ Hosp Birmingham, Womens & Childrens NHS Fdn Trust, Birmingham, W Midlands, England

[5] Univ Hosp Birmingham, Birmingham, W Midlands, England

[6] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England

[7] Miscarriage Assoc, Wakefield, England

[8] Univ Hosp Coventry & Warwickshire NHS Trust, Univ Hosp Coventry, Coventry, W Midlands, England

[9] East Lancashire Hosp NHS Trust, Burnley Gen Teaching Hosp, Burnley, Lancs, England

[10] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester, Lancs, England

[11] Univ Coll London Hosp NHS Fdn Trust, Univ Coll Hosp, London, England

[12] Guys & St Thomas NHS Fdn Trust, Assisted Concept Unit, London, England

[13] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England

[14] Kings Coll Hosp NHS Fdn Trust, London, England

[15] Queen Mary Univ London, Barts & London Sch Med & Dent, Barts Res Ctr Womens Hlth, London, England

[16] Univ Hosp Crosshouse, Ayrshire Matern Unit, Kilmarnock, Scotland

[17] Royal Bolton Hosp, Bolton NHS Fdn Trust, Bolton, England

[18] West Middlesex Univ Hosp, Chelsea & Westminster Hosp NHS Fdn Trust, Chelsea, England

[19] Univ Hosp Bristol NHS Fdn Trust, St Michaels Hosp, Bristol, Avon, England

[20] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Nottingham, England

[21] Univ Nottingham, Nottingham Clin Trials Unit, Sch Med, Nottingham Hlth Sci Partners,Queens Med Ctr, Nottingham, England

[22] Shrewsbury & Telford Hosp NHS Trust, Princess Royal Hosp, Shrewsbury, Salop, England

[23] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Singapore, Singapore

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2019年 / 380卷 / 14期

关键词：

DISEASE;

D O I：

10.1056/NEJMoa1812537

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 mu g 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, .) Thyroid peroxidase antibodies may increase the risk of miscarriage and preterm birth. In this controlled trial, the use of levothyroxine before conception and through birth did not improve live-birth rates among euthyroid women with such antibodies and a history of miscarriage or infertility.

引用

页码：1316 / 1325

页数：10

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