Iodine deficiency fetal brain

Potter BJ, Mano MT, Balling GB, Rogers PS, Martin DM and Hetzel BS (1981) Reversal of brain retardation in iodine-deficient fetal sheep. In Howell I, McC, Gawthome JM, White CL, eds. Trace Element Metabolism in Man and Animals, pp. 313-315. Springer Verlag Berlin, Heidelberg, New York. 

A. Brain damage caused by maternal/fetal/neonatal iodine deficiency A. Brain damage caused by maternal hypothyroidism ... 

Animal models in the marmoset and the sheep have been developed to study the effect of severe iodine deficiency on brain development. Both these models are characterised by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. 

The pituitary and brain, as well as brown adipose tissue, contain DI2 and DI3, which catalyze 5 - and 5-deiodination, respectively. Selenium deficiency alone has no effect on thyroid weight in rats, whereas iodine deficiency results in a 60% increase, and concurrent iodine and selenium deficiency results in a thyroid weight 148% above that of control animals. The principal physiological role of DI2 is the local intracellular production of T3. The role of DI3 has been proposed to protect fetal tissue from high levels of T3 and T4 during development by converting them to r T3 and r T4, respectively (Sunde 1997) (r = reverse). 

The realization that iodine deficiency in pregnancy has a pronounced effect on fetal, neonatal and childhood brain function has resulted in a large body of knowledge on the effects of thyroid hormone on brain and nervous-system development (see Grave, 1977 DeLong et ai, 1989 Stanbury, 1994 Bemal, 2002). 

The demonstration of the prevention of cretinism with iodized oil in a double-blind controlled trial in Papua New Guinea established the causal role of iodine deficiency in cretinism by an effect on the developing fetal brain (Pharoah et al, 1971). Cretinism could not be prevented unless the iodized oil was given before pregnancy, as injection during pregnancy was ineffective (Table 62.2). 

Early correction of hypothyroidism due to congenital defects in neonates has now become a standard practice in most developed countries in order to prevent longterm brain damage (Dussault and Glorieux, 1989). The more severe the fetal hypothyroidism, as indicated by bone retardation, the more Hkely are residual effects (Dussault and Glorieux, 1989). Such considerations indicate the urgent need for a preventive approach to the correction of iodine deficiency for developing countries, because treatment of individual cases is not usually possible. 

Three mechanisms have been suggested for the effect of iodine deficiency on fetal brain development. 

Other studies in the iodine-deficient rat confirm low fetal brain T3 levels despite a five-fold to ten-fold increase... 

Figure 64.3 Concentrations of T4, T3 and D2 activity in the brain of rat fetuses (left side) between the onset of fetal thyroid function (18dg) and birth (B) and in litters from pups until 4 weeks of postnatal age (right side) born from mothers on an iodine-deficient (LID) and iodine-supplemented (LID -H I) diet. Data (mean SEM) are from Obregon etal., (1991).

Iodine and thyroid hormones affect all stages of human development, from in utero life to adulthood. Iodine deficiency leads to insufficient production of thyroid hormones, which play a vital role in the process of early growth and development of many organs. During pregnancy, both maternal and fetal thyroid hormones are required for normal fetal brain development. Of them, maternal hormones constitute the main source in the first and the second trimesters, whereas the contribution of fetal hormones becomes more important in the third trimester (de Escobar et aL, 1985 Vulsma et ai, 1989). Many studies indicate that iodine deficiency and iodine-induced maternal-fetal hypothyroxinemia result in impairment of central nervous system (CNS) development during fetal and early postnatal life. 

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. 

Maternal and fetal hypothyroidism due to iodine deficiency results in significant changes in brain MR spectra. Early thyroxine therapy normalizes the levels of spectral metabolites. The decrease in NAA/Cr ratios, or absolute NAA levels, may be used as a primary indicator of intrauterine hypothyroxinemia-related subtle neuronal damage. In that context, MRS may also demonstrate the therapeutic effect of thyroxine in an objective manner. 

Iodine deficiency at any degree of severity causes maternal and fetal hypothyroxinemia. As thyroid hormones of the mother and the fetus must be kept at optimal levels, iodine prophylaxis should be provided, especially in iodine deficient areas. To establish normal fetal brain development, iodine supplementation must be started before pregnancy and should be continued during the gestational period. 

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