Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review

Hum Reprod Update. Sep-Oct 2011;17(5):605-19. doi: 10.1093/humupd/dmr024. Epub 2011 May 28.


Background: Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy.

Methods: Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register.

Results: From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies.

Conclusions: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Spontaneous / etiology
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / complications*
  • Epidemiologic Studies
  • Female
  • Humans
  • Hypothyroidism / complications*
  • Infertility, Female / etiology
  • Postpartum Thyroiditis / etiology
  • Pregnancy
  • Pregnancy Complications*
  • Pregnancy Outcome
  • Pregnancy Trimester, First / immunology
  • Pregnancy Trimester, First / metabolism
  • Premature Birth / etiology
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Thyroid Diseases / immunology