And maternal thyroid function

The link between iodine-deficiency related minor neurological disorders and maternal thyroid function during gestation... 

E.B. Man, W.S. Jones, R.H. Holden and E.D, Hellits, Thyroid function in human pregnancy. VIII. Retardation of progeny aged 7 years relationship to maternal age and maternal thyroid function. Am. J. Obstet. Gynecol.Ill 905-910 (1971). 

G. N. Burrow, D. A. Fisher, and R R. Larsen Mechanisms of disease maternal and fetal thyroid function. New England Journal of Medicine 331, 1072 (1994). 

The fetus is totally dependent on maternal iodine supply throughout gestation, and on thyroxine supply during the first trimester of pregnancy for normal neurological development and nervous system maturation. It is therefore imperative that TH synthesis is adequate and is met with the appropriate iodine intake. Accordingly, it is important to know the trimester-specific reference intervals for THs and other thyroid functions in pregnancy. 

The observations relating to iodine deficiency in pregnancy are firstly those concerned with maternal thyroid function and maternal goiter. Maternal urinary iodine (UI) excretion is the usual method of assessing iodine status in the population at risk or the individual, and is discussed below. Neonatal indicators of maternal iodine deficiency are goiter and neurointellectual impairment. 

Gestational hypothyroidism has been associated with severe complications, such as hypertension, preterm birth, low birth weight, placental abruption and fetal death by Leung et al, (1993) and Allan et al. (2000). Many studies in children of hypothyroid pregnant women including Mans group (1976, 1991), and many later ones (Liu et al, 1994 Smit et al, 2000 Klein et al, 2001 Mitchell and Klein, 2004), have demonstrated the importance of maternal thyroid function on the neurodevelopmental evolution of the child. 

The figure shows that a normal General Cognitive Index requires adequate maternal iodine nutrition conditions and a thyroid function. CGI, General Cognitive Index. UIE, urine iodine excretion. TSH, serum thyrotropin. 

Endemic cretinism has been a common finding in the mountains or isolated regions, such as the Alps or the Himalayas and has been described or depicted in drawings over the centuries. McCarrison (1917) studied this condition in the Himalayas, describing two types of cretinism the nervous and myxedematous types. He already suspected the influence of the maternal thyroid function on the fetus. Early observations in the Alps (Hunziker-Shild, 1915) already reported that the fetus could receive the hormone from the mother, and proposed the prophylactic administration of iodine from conception. 

Iodine deficiency and ADHD maternal thyroid function vs. ADHD... 

When neurological results were related to early-pregnancy maternal thyroid function, it was seen that all 11 ADHD+ children were born to the ID area mothers whose thyroid function proved more heavily compromised than that of the 5 ADHD— mothers, and that 7/8 (87.5%) of the ID area mothers who experienced thyroid failure generated ADHD+ children. It is worth noting, however, that individual TSH levels fell consistently within the normal range in all but two of these women,... 

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. 

Thyroid hormones, T3 and T4, have been i cwn to play significant but poorly understood roles in development and differentiation of rodent and human brain (1-7). In the human, disorders of maternal and fetal thyroid function include maternal and secondary fetal iodine deficiency, maternal hypothyroidism or hyperthyroidism, as well eis disorders related to deficient fetal autcxiomous thyroid hormcaie secretion, i.e., goiter or i radic oongenitel hypothyroidism. These disorders are identifiable causes of mental retardation (4, 8, 9, 10), cer ral peilsy (11, 12), and other significant neurological abnormalities (5, 6, 11) ... 

Iodine Deficiency Disorders (IDD) are a major international public health problem (1). The effects of iodine deficiency occur at all ages, but are particularly important during the period of fetal development. The available epidemiological evidence has been complemented by experimental studies of fetal development in animal models. These have focussed particularly on fetal brain development because of its obvious importance Definite effects have been observed in a variety of animal models - the rat, the marmoset and the sheep. In addition studies of the mechanisms involved have been carried out which have revealed the importance of maternal thyroid function for fetal brain development. 

The data reviewed reveal significant effects on fetal brain development. The study of the mechanisms in the sheep reveals the role of both maternal and fetal thyroid function. 

Maternal thyroid function and motor competence in the child. Develop. Med, and Child Neurology 23 76-82 (1981). 

Table 1 outlines the experimental design which we used. Methimazole (MMI) was used to block maternal and fetal thyroid function. Some of the MMI-treated dams received a replacement dose of T4 given by constant infusion, as described in detail elsewhere23. The main findings are summarized in Fig. 5, which shows the T4 and T3 concentrations in fetal carcass and brain. Comparison of the hormone levels in fetuses from C + MMI + T4 (or T + MMI + T4) dams with those from C + MMI (or T + MMI) mothers shows that infusion of T4 into the mothers not only ameliorates fetal deficiency of T4, but also of T3. This occurs without an increase of fetal plasma T3, suggesting that the fetal brain derived its T3 from local deiodination of T4. 

Pharoah POD, Ellis SM, Ekins RP, Williams ES, Maternal thyroid function, iodine deficiency and fetal development, Clin Endocrinol 5 159 (1976)... 

In the human, the concentration of reverse T3 (rT3), an iodothyronine generated from 5-deiodination of T4, in amniotic fluid (AF) far exceeds its concentration in maternal serum. Rat models of fetal hypothyroidism, maternal hypothyroidism and combined maternal-fetal hypothyroidism were enoployed to explore the source (s) of AF rT3 since it had earlier been suggested that AF rT3 concentration mi t be used as a means of diagnosing fetal hypothyroidism in utero. These studies indicated that AF rT3 content was influenced by maternal and not fetal thyroid function (Table 1) and that rT3 itself was poorly trani rted from maternal serum into the amniotic cavity. Fetal serum rT3 concentration is dependent ipon both maternal and fetal thyroid function. Suzuki et al., have also r rted that changes in rat AF rT3 concentration are mainly dependent ipon maternal thyroid function. These findings suggested to us that tissues in contact with both maternal serum and fetal serum, or maternal tissues and the... 

Table 1. Data on maternal thyroid function in pregnancy and measures of the... 

These data, indicating the importance of maternal thyroid function to fetal survival and development, are complemented by extensive animal data. Recent findings from the study of experimental animal models and more recently in man, indicate that there is a transfer of maternal thyroxine early in pregnancy. It would seem likely therefore that the effects of iodine deficiency on the fetus are... 

P. Bourdoux, Maternal and neonatal thyroid functions at birth in conditions of marginally low iodine intake, J Clin Endocrinol Metab. (September 1992 in press),... 

F. Delange, Effect of maternal thyroid function during pregnancy on fetal development, in "The Thyroid and Pregnancy", C. Beckers, and D. Reinwein, eds, Schattauer, Stuttgart, New York, p.7 (1991). 

Thorpe-Beeston JG and Nicolaides KH (1996) Maternal and Fetal Thyroid Function in Pregnancy New York The Parthenon Publishing Group. 

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