The role of thyroid hormone in fetal neurodevelopment

Abstract

Thyroid hormones are necessary for normal brain development during fetal and postnatal life. The stage at which the central nervous system becomes thyroid hormone sensitive, however, has not been clearly defined. There is increasing evidence from epidemiological studies and patient reports that these hormones are already needed for orderly development during the first trimester, when the fetus is entirely dependent on the maternal transfer of thyroxine, the main substrate for intracellular generation of the more active 3,5,3'-triiodothyronine for binding to the nuclear hormone receptors. A decrease in maternal circulating thyroxine during the first trimester, whether or not accompanied by increased circulating thyroid-stimulating hormone, may well result in irreversible mental and psychomotor impairments. The very frequent cause of this is an iodine intake insufficient to meet the requirements of the pregnant woman. It appears urgent to ensure the use of iodine supplements from before or very early in pregnancy, and to screen all women for hypothyroxinemia as early as possible. Maternal thyroxine continues to be important for the exposure of fetal tissues to adequate amounts of this hormone during the second and, possibly, the third trimesters. Premature birth, which interrupts this transfer, results in neonatal hypothyroxinemia. This is more severe the earlier it occurs during development, and is an important cause of the poorer mental and neuromotor development of many preterm infants. The possibility of supplying them with thyroxine during the neonatal period is being seriously tested.