Is neuropsychological development related to maternal hypothyroidism or tomaternal hypothyroxinemia?

Several recent publications have drawn attention to the role of the thyroid hormone status of the mother on the future neuropsychological development of the child. The screening of pregnant women for clinical or subclinical h ypothyroidism based on second trimester elevated maternal TSH values has be en proposed. Here, we have summarized present epidemiological and experimen tal evidence strongly suggesting that conditions resulting in first trimest er hypothyroxinemia (a low for gestational age circulating maternal free T- 4, whether or not TSH is increased) pose an increased risk for poor neurops ychological development of the fetus. This would be a consequence of decrea sed availability of maternal T-4 to the developing brain, its only source o f thyroid hormone during the first trimester; T-4 is the required substrate for the ontogenically regulated generation of T-3 in the amounts needed fo r optimal development in different brain structures, both temporally and sp atially. Normal maternal T-3 concentrations do not seem to prevent the pote ntial damage of a low supply of T-4, although they might prevent an increas e in circulating TSH and detection of the hypothyroxinemia if only TSH is m easured. Hypothyroxinemia seems to be much more frequent in pregnant women than either clinical or subclinical hypothyroidism and autoimmune thyroid d isease, especially in regions where the iodine intake of the pregnant woman is inadequate to meet her increased needs for T-4. It is proposed that the screening of pregnant women for thyroid disorders should include the deter mination of free T-4 as soon as possible during the first trimester as a ma jor test, because hypothyroxinemia has been related to poor developmental o utcome, irrespective of the presence of high titers of thyroid autoantibodi es or elevated serum TSH. The frequency with which this may occur is probab ly 150 times or more that of congenital hypothyroidism, for which successfu l screening programs have been instituted in many countries.