Negro, R., Schwartz, A., Gismondi, R., Tinelli, A., Mangieri, T., & Stagnaro-Green, A. (2010). Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. The Journal of Clinical Endocrinology and Metabolism, 95(9), E44-E48. https://doi.org/10.1210/jc.2010-0340
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab. 2010;95(9):E44-E48. doi:10.1210/jc.2010-0340
Negro, Roberto, et al. "Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy." The Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 9, 2010, pp. E44-E48.
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Mildly raised TSH linked to pregnancy loss in antibody-negative women
A prospective study of 4123 pregnant women without thyroid antibodies in southern Italy found that pregnancy loss affected about 6 out of 100 women with mildly raised early TSH. Women with lower TSH (thyroid-stimulating hormone) had about 4 out of 100 losses in the same study. Preterm delivery rates did not differ between these groups.
Key Findings
Pregnancy loss occurred in 127 of 3481 women (3.6%) with lower TSH and in 39 of 642 women (6.1%) with mildly raised TSH (P = 0.006).
Preterm delivery occurred in 4.7% of the lower TSH group and 5.1% of the mildly raised group. Very preterm delivery was 1.85% versus 0.93%. Neither difference was significant.
The analysis covered 4123 women negative for thyroid peroxidase antibody and not hyperthyroid. Of these, 3481 (84.4%) had lower TSH and 642 (15.6%) had mildly raised TSH.
After adjusting for smoking, logistic regression gave an odds ratio of 1.157 per point of TSH (95% CI 1.002 to 1.336, P = 0.047), suggesting a continuous relationship with miscarriage.
Free T4 was higher in the lower TSH group. Rates of pregnancy loss and preterm delivery were unrelated to free T4 levels.
Interpretation
This prospective cohort study followed pregnant women with normal thyroid antibodies and tracked early TSH against pregnancy loss and preterm delivery. Each one-point rise in early TSH was linked with higher odds of pregnancy loss after adjusting for smoking (odds ratio 1.157). Free T4 levels did not track with either outcome. The authors note that thyroglobulin antibody was not measured in this cohort. The findings support larger trials testing treatment for antibody-negative women with mildly raised TSH.
RRM Context
Restorative reproductive medicine looks for a treatable cause behind pregnancy loss. Thyroid function is a measurable part of that search. This study links mildly raised early TSH to more loss in women without thyroid antibodies. A randomized trial by the same group found that treating antibody-positive women with raised TSH reduced maternal and neonatal complications.
Our editorial summary of this paper, not the article's abstract.
Abstract
Context
The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter.
Objective
The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter.
Design
The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter.
Setting
The study was conducted at two ambulatory clinics of community hospitals in southern Italy.
Patients
A total of 4123 women were evaluated.
Intervention
There was no intervention.
Main Outcome Measures
The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured.
Results
The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups.
Conclusions
The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.
