Interventions for clinical and subclinical hypothyroidism in pregnancy

Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007752. doi: 10.1002/14651858.CD007752.pub2.


Background: Over the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective.

Objectives: To identify interventions used in the management of hypothyroidism and subclinical hypothyroidism in pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2009).

Selection criteria: Randomised controlled trials (RCTs) that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism in pregnancy with another intervention or placebo.

Data collection and analysis: Two review authors assessed trial eligibility and quality and extracted the data.

Main results: We included three RCTs of moderate risk of bias involving 314 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). One trial of 30 hypothyroid women compared levothyroxine doses, but only reported biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the three trials reported on childhood neurodevelopmental delay.There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and decreased incidence of moderate to advanced postpartum thyroiditis.

Authors' conclusions: Levothyroxine treatment of clinical hypothyroidism in pregnancy is already standard practice given the documented benefits from earlier non-randomised studies. Whether levothyroxine should be utilised in autoimmune and subclinical hypothyroidism remains to be seen, but it may prove worthwhile, given a possible reduction in preterm birth and miscarriage.Selenomethionine as an intervention in women with thyroid autoantibodies is promising, particularly in reducing postpartum thyroiditis. There is a probable low incidence of adverse outcomes from levothyroxine and selenomethionine. High-quality evidence is lacking and large-scale randomised trials are urgently needed in this area. Until evidence for or against universal screening becomes available, targeted thyroid function testing in pregnancy should be implemented in women at risk of thyroid disease and levothyroxine utilised in hypothyroid women.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Abortion, Spontaneous / prevention & control
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Hypothyroidism / drug therapy*
  • Pre-Eclampsia / prevention & control
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Outcome
  • Premature Birth / prevention & control
  • Randomized Controlled Trials as Topic
  • Selenomethionine / therapeutic use*
  • Thyroid Gland / immunology
  • Thyroiditis, Autoimmune / drug therapy
  • Thyroxine / therapeutic use*


  • Selenomethionine
  • Thyroxine