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 Sep;95(9):E44-8. doi: 10.1210/jc.2010-0340. Epub 2010 Jun 9.


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.

Publication types

  • Multicenter Study

MeSH terms

  • Abortion, Spontaneous / blood
  • Abortion, Spontaneous / epidemiology
  • Abortion, Spontaneous / etiology
  • Abortion, Spontaneous / immunology
  • Adult
  • Case-Control Studies
  • Embryo Loss / blood
  • Embryo Loss / epidemiology*
  • Embryo Loss / etiology
  • Embryo Loss / immunology
  • Female
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood*
  • Incidence
  • Osmolar Concentration
  • Parity / physiology
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Pregnancy Trimester, First / immunology
  • Reference Values
  • Thyrotropin / analysis
  • Thyrotropin / blood*
  • Young Adult


  • Immunoglobulins, Thyroid-Stimulating
  • Thyrotropin