Increased Pregnancy Loss Rate in Thyroid Antibody Negative Women with TSH Levels between 2.5 and 5.0 in the First Trimester of Pregnancy

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 T4, 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. (J Clin Endocrinol Metab 95: E44–E48, 2010)