The prevalence of thyroid dysfunction and autoimmunity in women with history of miscarriage or subfertility

Rima Smith, Aurelio Tobias Garces, Paul Smith, Lee Middleton, Kirandeep Sunner, Krystyna Baker, Samantha Farrell-Carver, Ruth Bender Atik, Rina Agrawal, Kalsang Bhatia, Justin Chu, Edmond Edi-Osagie, Ayman Ewies, Tarek Ghobara, Pratima Gupta, Davor Jurkovic, Yakoub Khalaf, Khashia Mulbagal, Natalie Nunes, Caroline OvertonSiobhan Quenby, Rajendra Rai, Nick Raine-Fenning, Lynne Robinson, Jackie Ross, Andrew Sizer, Rachel Small, Martin Underwood, Mark Kilby, Jane Daniels, Shakila Thangaratinam, Shiaoyng Chan, Kristien Boelaert, Arri Coomarasamy

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Objective To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. Design Observational cohort study. Setting A total of 49 hospitals across the United Kingdom between 2011 and 2016. Participants Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. Methods Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. Intervention None. Main Outcome Measure Rates of thyroid dysfunction. Results Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). Conclusions The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.
Original languageEnglish
Pages (from-to)2667–2677
JournalJournal of Clinical Endocrinology and Metabolism
Issue number8
Early online date17 Jun 2020
Publication statusPublished - 1 Aug 2020


  • miscarriage
  • preconception
  • prevalence
  • subfertility
  • thyroid autoimmunity
  • thyroid disease

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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