Towards optimization of thyroid hormone replacement therapy during pregnancy

Project summary

The hypothyroidism during pregnancy is associated with an increased risk of adverse pregnancy and child outcomes. Even mild maternal thyroid dysfunction adversely affects child cognitive development resulting in lower IQ scores and an increased risk of autism, ADHD and schizophrenia. As a consequence, current guidelines advocate treatment with levothyroxine (LT4) in over 5% of pregnant women. However, it is neither clear how and to what extent maternal LT4 crosses the placenta, nor how this transport is regulated (knowledge gap 1). We therefore lack essential information on optimal LT4 dose and dose-adjustment strategies during pregnancy. Furthermore, we recently showed that there is a tight balance between over- and under treatment. Current LT4 treatment is merely guided by maternal thyroid parameters, because reliable non-invasive markers of fetal TH status to monitor LT4 therapy are lacking (knowledge gap 2). The identification of accurate markers of fetal thyroid status is therefore of major importance, as this will allow tailored treatment of pregnant women to optimize development of their unborn children. The overall aim of this project is to address these two major knowledge gaps and thereby provide a scientific framework that allows optimization of TH replacement therapy during pregnancy. Key objectives are: 1) To unravel how transport of maternal T4 across the placenta is regulated; 2) To characterize the natural course of the different TH metabolites during pregnancy; 3) To identify and validate the best marker of fetal thyroid state in maternal serum. 

Through further unraveling TH physiology during pregnancy and developing monitoring strategies, we expect to improve management of LT4 treated mothers during pregnancy. This will have a beneficial effect on neurocognitive outcome of their children, positively affecting overall lifetime achievements and general health.