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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

1
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.

Abstract

CONTEXT:

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

OBJECTIVE:

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.

DESIGN:

This was a historical cohort analysis.

PATIENTS:

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.

MAIN OUTCOME MEASURES:

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

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
25057882
DOI:
10.1210/jc.2014-1954
[Indexed for MEDLINE]

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