Maternal hypothyroxinemia

Morreale de Escobar G, Obrcgon MJ, Escobar del Rey F. 2000. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia J Clin Endocrinol Metab 85(11) 3975-3987. 

The neurological abnormalities observed in neurological cretinism seem to be caused by maternal hypothyroxinemia during the first period of brain development, early in pregnancy. In iodine deficiency the maternal plasma T4 is low, even if plasma T3 and TSH are normal. 

Development of the neocortex can be affected by short periods of maternal hypothyroxinemia, before the onset of fetal thyroid function. Therefore, to maintain normal thyroxinemia in the mother is of maximal importance to maintain normal T3 levels in the fetal brain. 

Maternal hypothyroxinemia due to Iodine deficiency effects on fetal neurocognitive development... 

The above-mentioned facts form the basis of a new concept of the adverse effects of not only maternal hypothyroidism, but also maternal hypothyroxinemia without overt hypothyroidism, on fetal brain development. This concept focuses on the necessity for therapeutic correction of maternal hypothyroxinemia detected in pregnancy. MRS, a quantitative laboratory and imaging technique, may be used to show the effects of hypothyroxinemia due to iodine deficiency and its correction in the human brain in an objective manner. 

The ADHD prevalence of almost 90% in children born to hypothyroxinemic mothers seems to point to a strong association of this neuropsychological disorder with ID-related early gestational maternal hypothyroxinemia. 

Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia drew attention to the relationship between low maternal free-thyroxine concentrations and impaired neuropsychological development in children (Morreale de Escobar et al., 2004). This hypothesis has since been supported by further clinical and basic data, reinforcing the idea that screening programs should be implemented systematically in order to correct any maternal thyroid underfunction promptly and ultimately prevent fetal brain damage. 

Why Should We Care about lodine-Deficiency-Related Maternal Hypothyroxinemia ... 

Maternal hypothyroxinemia also occurred in women who had started iodine supplementation at least 2 years prior to becoming pregnant and who were also given iodine-containing multivitamin supplements, though to a lesser degree (16%). 

In our series, maternal hypothyroxinemia occurred in the vast majority (93.1%) of pregnant women in the second and third trimesters. This indicates that, if we confined the screening of maternal thyroid function to the first trimester, we would miss almost all hypothy-roxinemic women whose fetuses would thus be exposed to inadequate availability of maternal T4 and put at risk of impaired neurological development. 

In conclusion, not only screening, but also monitoring of maternal thyroid function should be encouraged in moderately iodine-deficient areas, in order to correct maternal hypothyroxinemia promptly and consequently prevent irreversible neurological damage in progeny. 

The importance of the transfer of thyroid hormones from the mother to the fetus during the second half of pregnancy in humans has received increasing attention (Burrow et ai, 1994). Recently, it has become evident that maternal hypothyroxinemia results not only in the birth of children with neurological cretinism, but also in decreased mental and psychomotor development of the rest of the population without cretinism (Beichrodt and Born, 1994). 

Because of obvious ethical strictures, direct evidence of a causal relationship between early maternal hypothyroxinemia and mental development can only be obtained in animal models. Lucio et al (1997) and Berbel et al (2001) have shown that neocortical cell migration is defective in the progeny of severely hypothyroid rat dams that were... 

Maternal hypothyroxinemia is not detected in most pregnant women early in pregnancy, since it does not necessarily result in cfinical or subcfinical hypothyroidism. The mother herself may synthesize and secrete enough T4 and T3 to meet her own needs, but the amount of T4 reaching the fetus might not be sufficient for normal neurodevelopment. 

Maternal hypothyroxinemia, caused by iodine intake which fails to meet the increased needs imposed by the conceptus, is hkely to be much more frequent than primary thyroid failure and thyroid autoimmune disease. 

In view of the evidence, which shows a relationship between early maternal hypothyroxinemia and poor neurodevelopment outcome, screening for low FT4 in prenatal or early gestation is mandatory. 

A similar situation, such as subclinical hypothyroidism, could arise with iodine deficiency causing maternal hypothyroxinemia or frank hypothyroidism. Dietary iodine deficiency is potentially the most likely cause therefore, it would be prudent to screen for iodine deficiency or optimize dietary iodine intake. 

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