Levothyroxine supplementation trials in preconception and pregnant women

Thyroid disorders are common in women of childbearing age, representing the second most prevalent endocrine disorder in this population. Low thyroid function preconception and during pregnancy has been associated with a range of adverse outcomes including subfertility, miscarriage, preterm birth, and ongoing health problems in the neonate. Levothyroxine (LT4) treatment is routinely used in women with overt hypothyroidism (OH) to achieve a euthyroid status and consequently reduce the risk of these adverse outcomes. However, in other groups, such as those with subclinical hypothyroidism (SCH) or thyroid autoimmunity, the evidence is less clear and subsequently guidelines differ in their recommendations. Here we explore key trials exploring the use of LT4 in different types of thyroid disorder, including OH, SCH, isolated hypothyroxinemia, and thyroid autoimmunity. We examine how these disorders are defined in different trials, the specifics of the populations included, and the varying timing and dosage of LT4. By exploring the limitations of these trials and the interactions between results, we highlight issues for future research and practical considerations for policy-makers and clinicians caring for women with low thyroid function during preconception and pregnancy.