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Interventions for clinical and subclinical hypothyroidism in pregnancy

  • Review
  • Intervention

Authors

  • Sally M Reid,

    Corresponding author
    1. The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia
    • Sally M Reid, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, 5006, Australia. sally.reid@adelaide.edu.au.

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  • Philippa Middleton,

    1. The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia
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  • Mary C Cossich,

    1. Women's and Children's Hospital, Department of Paediatrics, Adelaide, South Australia, Australia
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  • Caroline A Crowther

    1. The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia
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Abstract

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 methods

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.

Plain language summary

Interventions to reduce harm to women and their children from untreated low levels of thyroid hormone in pregnancy

The thyroid is a butterfly-shaped gland at the front of the oesophagus/throat that produces thyroid hormone. Thyroid hormone helps the body to make energy, keeps body temperature regulated and assists other organs in their functions. Hypothyroidism (a deficiency of thyroid hormone) is a relatively common illness that can cause fatigue, constipation, muscle cramps and weakness, hair loss, dry skin, intolerance to cold, depression and weight gain. Medication is with levothyroxine. Selenium is a trace element that changes the expression of selenoproteins. These act as antioxidants and appear to decrease thyroid inflammation in autoimmune thyroiditis. Pregnant women with subclinical hypothyroidism have abnormal thyroid hormone levels but no symptoms. They are at a increased risk of miscarriage, pre-eclampsia and preterm birth with impaired neuropsychological development in the child.

We identified three randomised studies involving only 314 pregnant women with hypothyroidism. In one trial of 115 women with thyroid autoantibodies but normal thyroid hormone levels, levothyroxine clearly reduced the risk of preterm birth by a mean of 72% compared with no treatment. The risk of women developing pre-eclampsia was not reduced, but there was a trend toward a reduction in miscarriage. In a study of 169 women with autoimmune hypothyroidism, supplementation with selenium did not decrease preterm birth rates or pre-eclampsia, but appeared to reduce moderate to severe inflammation of the thyroid gland and thyroid dysfunction after the birth. The third study looked at different doses of levothyroxine on thyroid hormone levels.

Levothyroxine is an established treatment for women with symptomatic hypothyroidism, but it may also benefit women with low thyroid levels who do not have symptoms. Selenium also shows promise for women with hypothyroidism but needs further testing. Until we know if screening all pregnant women for hypothyroidism is a good idea, those likely to be at risk of thyroid disease should have their thyroid function tested early in pregnancy.

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