Does autoimmune thyroid disease increase miscarriage

Autoimmune thyroid disease (Hashimoto's) increases miscarriage and obstetrical complications. 

There is a significant association between the presence of thyroid autoimmunity and a higher miscarriage rate, but it is only an association and not cause/effect relationship.

Within a large database of people who initiated levothyroxine treatment from 2001 to 2009 in the U.K., 7,987 of child-bearing age and 1,013 pregnancies in which treatment began at least 6 months prior to conception were identified. TSH level exceeded 2.5 mU/L — the recommended upper level in the first trimester — in 46% of women of child-bearing age who were treated with levothyroxine. Among those whose TSH was measured during the first trimester, 62.8% had TSH levels exceeding 2.5 mU/L. Further, 7.4% had TSH levels exceeding 10 mU/L. Miscarriage risk was higher in women with TSH greater than 2.5 mU/L in the first trimester vs. those with TSH ranging from 0.2 mU/L to 2.5 mU/L in the first trimester. Adjustments for age, year of pregnancy, diabetes and social class were made (P=.008). Miscarriage risk was also higher in women with TSH ranging from 4.51 mU/L to 10 mU/L (OR=1.80; 95% CI, 1.03-3.14) and TSH exceeding 10 mU/L (OR=3.95; 95% CI, 1.87-8.37). Risk for miscarriage, however, was not higher in those with TSH ranging from 2.51 mU/L to 4.5 mU/L (OR=1.09; 95% CI, 0.61-1.93). "The best pregnancy outcomes were seen in women with target TSH levels, and a strong risk of miscarriage was present at TSH levels exceeding 4.5 mU/L" the researchers wrote.


Miscarriage is a common occurrence and as many as 31% of pregnancies end in a miscarriage when sensitive human chorionic gonadotropin (hCG) assays are used, of which about one-third will be noticed by the mother.  The incidence of two miscarriages is 2–4% and the incidence of three consecutive losses is less than 1%. Recurrent Pregnancy loss: genetic, anatomic, infectious, smoking, alcohol and endocrine factors (diabetes mellitus, hyperprolactinemia) and antibodies (Lupus, AITD).  Here are the associations:


Co-segregation of other autoimmune disorders 
These studies excluded or analyzed separately SLE+, antiphospholipid, anticardiolipin) 

Direct dose-response relationship to miscarriage. (fig 1,2) 
only one study of 15 women with h/o recurrent miscarriage did find higher thyroperoxidase (TPO) antibody titers [group1] and avidity in TPO-positive women who aborted than in women with TPO antibodies who had a term delivery [group 2] 

Confounder of age 
TPO-positive women are 0.7 years older than their TPO-negative counterparts (P < 0.001). This appears to be a small and negligible difference, but around this age especially there is a sharp increase in the rate of spontaneous abortions. The rate among women aged 25–29 is 10.7%, in the age group 30–34 it is 14.2% and in the group aged 35–39 years it is 26.2% 

Confounder Mild Thyroid failure
Euthyroid women with TPO antibodies have slightly higher TSH values than those without antibodies; this may indicate less thyroidal reserve in times of greater demand for thyroid hormones, such as in pregnancy. On average, TSH levels were 0.81mU/l higher (P ¼ 0.005) in antibody positive women. Note: it is not so much the diagnosis of overt vs. subclinical hypothyroidism that mattered in relation with pregnancy outcome but mainly the adequacy of levothyroxine treatment. The outcome of pregnancy was retrospectively compared in 27 women with hypothyroidism (of many etiologies) already known before pregnancy and who received an adequate levothyroxine treatment with 24 women in whom levothyroxine treatment was not adequately adjusted during gestation and who, hence, did not reach euthyroidism. When the treatment was not adequate, pregnancy ended with abortion in 60 and 71% of overt and subclinical hypothyroid women, respectively, with an increased prevalence of preterm deliveries. Conversely, in hypothyroid pregnant women who received an adequate treatment, the frequency of abortions was minimal and pregnancies carried to term without complications. (Fig 3)


Updated 12-21-2014
References
1. Thyroid autoimmunity and miscarriage. Mark F Prummel and Wilmar M Wiersing. European Journal of Endocrinology (2004) 150 751–755. 
2. Overt and Subclinical Hypothyroidism Complicating Pregnancy M. Abalovich, S. Gutierrez, G. Alcaraz, G. Maccallini, A. Garcia, and O. Levalle. THYROID Volume 12, Number 1, 2002 
3. Daniel Glinoer et al. Risk of Subclinical Hypothyroidism in Pregnant Women with Asymptomatic Autoimmune Thyroid Disorders: J Clin Endocrinol Metab. 1994 Jul;79(1):197-204. 
4. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O 2002 Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 12:63–68
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