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Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence

BMJ 2011; 342 doi: (Published 09 May 2011) Cite this as: BMJ 2011;342:d2616
  1. Shakila Thangaratinam, senior lecturer/consultant in obstetrics and gynaecology and clinical epidemiology1,
  2. Alex Tan, academic foundation trainee2,
  3. Ellen Knox, consultant obstetrician/subspecialist in fetal medicine3,
  4. Mark D Kilby, professor of fetal medicine23,
  5. Jayne Franklyn, professor of medicine2,
  6. Arri Coomarasamy, reader/consultant gynaecologist/subspecialist in reproductive medicine and surgery2
  1. 1Centre for Health Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
  2. 2School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT
  3. 3Fetal Medicine Centre, Birmingham Women’s Foundation Trust, Edgbaston, Birmingham B15 2TG
  1. Correspondence to: A Coomarasamy a.coomarasamy{at}
  • Accepted 2 March 2011


Objectives To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women.

Design Systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth.

Study selection Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes.

Data synthesis Odds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model.

Results 30 articles with 31 studies (19 cohort and 12 case-control) involving 12 126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12 566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P<0.001). For case-control studies the odds ratio for miscarriage was 1.80, 1.25 to 2.60; P=0.002). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01). Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48, 0.25 to 0.92; P=0.03). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31, 0.11 to 0.90).

Conclusion The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.


  • Contributors: AC conceived the review. EK, ST, and AT performed the search, study selection, and data extraction. ST, AT, and AC analysed the results. ST, AC, JF, and MDK drafted the manuscript. All authors provided input into the development of the manuscript. All authors have approved the final manuscript. AC is guarantor.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The authors have been funded by the NIHR (National Institute of Health Research, UK) EME Programme (09-100-10) to conduct a multicentre placebo-controlled randomised trial on the pregnancy effects of levothyroxine treatment in thyroid antibody positive women with normal thyroid function (the TABLET trial).

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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