Management of hyperthyroidism in pregnancy; data from a large UK primary care cohort

Study type
Protocol
Date of Approval
Study reference ID
18_093
Lay Summary

Thyroid hormones are essential for normal development of the unborn child's nervous system. Hyperthyroidism occurs when the thyroid gland produces too much thyroid hormone and affects around 1 in 200 pregnancies. Untreated hyperthyroidism in pregnancy can result in unwanted outcomes such as miscarriage or being born too early. Effective treatment is therefore vital. However, there are concerns around how well hyperthyroidism is managed in pregnancy and the safety of antithyroid drugs (carbimazole and propylthiouracil). Current guidelines recommend using both drugs at different stages of pregnancy: propylthiouracil in the first three months, to avoid possible harm to the developing child, then switching to carbimazole to avoid possible propylthiouracil-related liver damage. An alternative approach is to permanently treat hyperthyroidism before pregnancy by removing the thyroid gland or using radioiodine. However, we do not know which approach leads to better thyroid control during pregnancy, or how well drug treatment guidelines are being followed. This study will first describe how many UK pregnant women with hyperthyroidism receive each treatment, then examine the impact of treatment on thyroid hormone levels during pregnancy. Identifying which treatment is most effective, and any shortcomings in management, will inform guidelines for better management of hyperthyroidism in pregnancy.

Technical Summary

Hyperthyroidism is common in women of childbearing age and is associated with adverse pregnancy and neonatal outcomes; optimal treatment is therefore vital. However, there are concerns surrounding the adequacy of its management in pregnancy and the safety of the two main antithyroid drugs (carbimazole and propylthiouracil). Current guidelines recommend a combination approach: propylthiouracil in the first trimester, to avoid potential teratogenicity with carbimazole, then changing to carbimazole to avoid potential propylthiouracil-induced liver damage. Definitive treatment of hyperthyroidism (with radioiodine or thyroidectomy) before pregnancy is also recommended as an alternative to antithyroid drug treatment. However, data on guideline adherence and adequacy of thyroid control in pregnant women with hyperthyroidism in the UK are lacking. We will undertake a descriptive analysis of trends in UK management of hyperthyroidism before and during pregnancy since 2001. Using a cohort design and multivariable logistic regression we will then assess whether definitive treatment before pregnancy results in better thyroid status during pregnancy (defined by thyroid-stimulating hormone and free thyroxine levels within UK reference ranges). We will also assess whether the combination drug approach results in a deterioration of thyroid status. The findings will be key to optimising treatment strategies for hyperthyroidism before and during pregnancy.

Health Outcomes to be Measured

Thyroid status during pregnancy

Collaborators

Caroline Minassian - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Caroline Minassian - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Bijay Vaidya - Collaborator - University of Exeter
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Onyebuchi Okosieme - Collaborator - Cardiff University
Peter Taylor - Collaborator - Cardiff University
Sara Thomas - Collaborator - Not from an Organisation
William Hamilton - Collaborator - University of Exeter

Linkages

HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;Pregnancy Register