Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes

J Clin Endocrinol Metab. 2012 Dec;97(12):4464-72. doi: 10.1210/jc.2012-2540. Epub 2012 Sep 26.


Context: Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant.

Objective: We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes.

Setting and participants: The study used data from the prospective mother-child cohort "Rhea" study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroid hormones (TSH, free T(4), and free T(3)) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders.

Main outcome measures: Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates.

Results: The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1-8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1, 95% CI 1.2-8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth.

Conclusions: High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Cohort Studies
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / epidemiology
  • Diabetes, Gestational / etiology*
  • Female
  • Gestational Age
  • Greece / epidemiology
  • Humans
  • Infant, Newborn
  • Parturition / blood
  • Parturition / immunology
  • Parturition / physiology
  • Pregnancy
  • Pregnancy Complications / blood*
  • Pregnancy Complications / epidemiology*
  • Pregnancy Outcome / epidemiology*
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, First / immunology
  • Pregnancy Trimester, Second / blood
  • Pregnancy Trimester, Second / immunology
  • Risk Factors
  • Thyroid Diseases / blood
  • Thyroid Diseases / epidemiology*
  • Thyroid Diseases / immunology
  • Thyroid Function Tests / statistics & numerical data
  • Young Adult


  • Autoantibodies