Isolated maternal hypothyroxinemia during pregnancy: Knowns and unknowns

Isolated maternal hypothyroxinemia (IMH) during pregnancy is defined as a low maternal T4 in the absence of TSH elevation. As IMH is common, with a prevalence of 1-2% in iodine-sufficient populations, and early research has suggested adverse effects on fetal neurodevelopment, it has been the focus of many studies in the last decade. In the current review, we first discuss the significance of IMH based on data from animal models and recent discoveries regarding the role of thyroid hormone on neurodevelopment. We address issues surrounding the definition and prevalence of this entity and discuss new insights into the etiologies, clinical consequences and management of IMH. A number of large cohort studies have investigated the effects of IMH on the risk of various pregnancy complications and child neurodevelopment. We review these studies in detail and describe their limitations. We discuss the available research on management of IMH, including two recent randomized controlled trials (RCTs). Finally, we delineate the remaining uncertainties in this field and emphasize the need for a sufficiently powered, placebo-controlled RCT on the treatment of IMH early in the first trimester of pregnancy. Page 2 of 48