TSH Levels and Risk of Miscarriage in Women on Long-Term Levothyroxine

TSH Levels and Risk of Miscarriage in Women on Long-Term Levothyroxine: A Community-Based Study. Taylor PN 1, Minassian C, Rehman A, Iqbal A, Draman MS, Hamilton W, Dunlop D, Robinson A, Vaidya B, Lazarus JH, Thomas S, Dayan CM, Okosieme OE. J Clin Endocrinol Metab. 2014 Oct;99(10):3895-902.
Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine. 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.
Forty-six percent of levothyroxine-treated women aged 18-45 years had a TSH level greater than 2.5mU/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.
COMMENT-This study clearly shows that many, or most, women out in the community in early pregnancy, on T4 replacement, have at least sub-clinical hypothyroidism and are at greater risk of miscarriage (in part because many are TPO Ab+). This is a loud call for increased attention to TSH levels in women before and during  pregnancy, and in the mind of this reader, another demand for universal TSH testing in early pregnancy.