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J Clin Endocrinol Metab. 2014 Oct;99(10):3895-902. doi: 10.1210/jc.2014-1954. Epub 2014 Jul 24.

TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study.

Author information

Thyroid Research Group (P.N.T., M.S.D., J.H.L., C.M.D., O.E.O.), Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; Department of Social and Community Medicine (P.N.T) and Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology (A.I., C.M.D.), University of Bristol, Bristol BS13NY, United Kingdom; Faculty of Epidemiology and Population Health (C.M., S.T.), London School of Hygiene and Tropical Medicine, London EC1M 6BQ, United Kingdom; Department of Internal Medicine (A.Re.), Akron General Medical Center, Akron, Ohio 44308; University of Exeter Medical School (W.H.), Exeter EX4 4PY, United Kingdom; Departments of Obstetrics and Gynecology (D.D.) and Diabetes and Endocrinology (A.Ro.), Royal United Hospital, Bath BA2 7AY, United Kingdom; Department of Endocrinology (B.V.), Royal Devon and Exeter Hospital and University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Department of Endocrinology and Diabetes (O.E.O.), Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil CF47 9DT, United Kingdom.



Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine.


The objective of the study was to determine the relationship between TSH levels and pregnancy outcomes in levothyroxine-treated women in a large community-based database.


This was a historical cohort analysis.


Individuals with a first prescription of levothyroxine from 2001 through 2009 (n = 55 501) were identified from the UK General Practice Research Database (population 5 million). Of these, we identified 7978 women of child-bearing age (18-45 y) and 1013 pregnancies in which levothyroxine had been initiated at least 6 months before conception.


TSH, miscarriage/delivery status, and obstetric outcomes were measured.


Forty-six percent of levothyroxine-treated women aged 18-45 years had a TSH level greater than 2.5 mU/L (recommended upper level in the first trimester). Among pregnant women who had their TSH measured in the first trimester, 62.8% had a TSH level greater than 2.5 mU/L, with 7.4% greater than 10 mU/L. Women with TSH greater than 2.5 mU/L in the first trimester had an increased risk of miscarriage compared with women with TSH 0.2-2.5 mU/L after adjusting for age, year of pregnancy, diabetes, and social class (P = .008). The risk of miscarriage was increased in women with TSH 4.51-10 mU/L [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.03, 3.14)] and TSH greater than 10 mU/L (OR 3.95, 95% CI 1.87, 8.37) but not with TSH 2.51-4.5 mU/L (OR 1.09, 95% CI 0.61, 1.93).


The majority of levothyroxine-treated women have early gestational TSH levels above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of thyroid hormone replacement in early pregnancy.

[Indexed for MEDLINE]

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