Future Research Directions


In developing the Guidelines the task force frequently struggled with the paucity of high-quality double-blind placebo controlled trials in the field of thyroid and pregnancy. In fact, only 18 of the 76 recommendations (24%) in the present Guidelines were graded at the highest USPSTF Level (Level A). The Guidelines task force identified topics for future research that will be critical in resolving many of the unanswered questions in the field of thyroid and pregnancy. Of concern to the task force is that the double-blind placebo control studies either recently completed, or presently underway, began screening and intervention after the first trimester. As such these studies will not be able to address the impact of LT4 treatment in the first trimester in women with SCH, isolated hypothyroxinemia, or thyroid antibody positivity on the mother and developing fetus. A trial that screens women preconception and then randomizes women with SCH or isolated hypothroxinemia and TAb+ euthyroid women to either a treatment or no treatment arm is needed. The task force is aware of the difficulties inherent in performing such a trial, and the ethical challenges to be faced. Nevertheless, we believe that such a trial is feasible, can be ethically performed with appropriate study design and safeguards, and will yield invaluable information related to the optimal care of the pregnant women and the developing fetus. Other areas for future research include:
  • A comprehensive cost-effectiveness study of screening for thyroid disease in pregnancy.
  • A study evaluating the impact of iodine supplementation in pregnant women with the mildest form of iodine deficiency (median urinary iodine concentrations 100–150 μg/L)
  • A study focused on the effects of iodine supplementation during lactation on infant thyroid function and cognition.
  •  A study to determine safe upper limits for iodine ingestion in pregnancy and lactation.
  • A comprehensive study to asses the iodine status of pregnant and lactating women in the United States.
  • A trial assessing the optimal targeted FT4 level in pregnant women treated for hyperthyroidism.
  • Another well powered, prospective, randomized interventional trial of LT4 in euthyroid patients who are TPOAb+ for the prevention of spontaneous abortion and preterm delivery
  • A study to evaluate the impact of LT4 therapy in TAb+ euthyroid women with recurrent spontaneous abortion.