The Prevalence of Thyroid Dysfunction and Autoimmunity in Women With History of Miscarriage or Subfertility

Author:

Dhillon-Smith Rima K123ORCID,Tobias Aurelio1,Smith Paul P123,Middleton Lee J4,Sunner Kirandeep K4,Baker Krystyna5,Farrell-Carver Samantha4,Bender-Atik Ruth6,Agrawal Rina7,Bhatia Kalsang8,Chu Justin J123,Edi-Osagie Edmond9,Ewies Ayman10,Ghobara Tarek7,Gupta Pratima11,Jurkovic Davor12,Khalaf Yacoub13,Mulbagal Khashia14,Nunes Natalie15,Overton Caroline16,Quenby Siobhan7ORCID,Rai Raj17,Raine-Fenning Nick18,Robinson Lynne3,Ross Jackie19,Sizer Andrew20,Small Rachel10,Underwood Martyn20,Kilby Mark D13,Daniels Jane21,Thangaratinam Shakila22,Chan Shiao23,Boelaert Kristien1,Coomarasamy Arri123

Affiliation:

1. Institute of Metabolism and Systems Research, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK

2. Tommy’s Centre for Miscarriage Research, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK

3. Birmingham Women’s and Children’s Foundation Trust, Birmingham, UK

4. Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, UK

5. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK

6. The Miscarriage Association, Wakefield, UK

7. University Hospital Coventry, University Hospitals Coventry & Warwickshire NHS Trust, UK

8. Burnley General Hospital, East Lancashire Hospitals NHS Trust, UK

9. St Mary’s Hospital, Central Manchester University Hospital Foundation Trust, UK

10. City Hospital, Birmingham, UK

11. University Hospital Birmingham, Birmingham, UK

12. University College Hospital, University College Hospitals NHS Foundation Trust, London, UK

13. Assisted Conception Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

14. Royal Bolton Hospital, Bolton NHS Foundation Trust, UK

15. West Middlesex Hospital, Chelsea and Westminster NHS Foundation Trust, UK

16. St Michaels Hospital, University Hospitals Bristol NHS Foundation Trust, UK

17. St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK

18. Queens Medical Centre, Nottingham University Hospitals NHS Trust, UK

19. Early Pregnancy and Gynaecology Assessment Unit, King’s College Hospital NHS Foundation Trust, London, UK

20. The Princess Royal Hospital, The Shrewsbury and Telford NHS Trust, UK

21. Nottingham Clinical Trials Unit, University of Nottingham, School of Medicine, Nottingham Health Sciences Partners, Queens Medical Centre, Nottingham, UK

22. Barts Research Centre for Women’s Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

23. Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract

Abstract 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.

Funder

Efficacy and Mechanism Evaluation program

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference29 articles.

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5. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review;van den Boogaard;Hum Reprod Update.,2011

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