Iodine deficiency and brain development in the first half of pregnancy

Abstract

An inadequate supply of iodine during gestation results in damage to the foetal brain that is irreversible by mid-gestation unless timely interventions can correct the accompanying maternal hypothyroxinemia. Even mild to moderate maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review mainly focuses on iodine and thyroid hormone economy up to mid-gestation, a period during which the mother is the only source for the developing brain of the foetus. The cerebral cortex of the foetus depends on maternal thyroxine (T 4 ) for the production of the 3 0 ,3,5-tri-iodothyronine (T 3 ) for nuclear receptor-binding and biological effectiveness. Maternal hypothyroxinemia early in pregnancy is potentially damaging for foetal brain development. Direct evidence has been obtained from experiments on animals: even a relatively mild and transient hypothyroxinemia during corticogenesis, which takes place mostly before mid-gestation in humans, affects the migration of radial neurons, which settle permanently in heterotopic locations within the cortex and hippocampus. Behavioural defects have also been detected. The conceptus imposes important early changes on maternal thyroid hormone economy that practically doubles the amount of T 4 secreted something that requires a concordant increase in the availability of iodine, from 150 to 250-300 mg I day 21 . Women who are unable to increase their production of T 4 early in pregnancy constitute a population at risk for having children with neurological disabilities. As a mild to moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia, the birth of many children with learning disabilities may be prevented by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible, in order to ensure that their requirements for iodine are met.

Iodine Status of Pregnant Women and Their Progeny in the Minho Region of Portugal

“…Other potential indices of ID, such as neonatal TSH, are not completely reliable due to many factors, including the timing of sample collection (1)(2)(3)(4)32,35,36). Although the present study showed that the newborns met the WHO criteria for desirable serum TSH concentrations (considered iodine sufficient if less than 3% of the newborns have TSH >5 mU=L), it is now well recognized that the regulation of TSH secretion in the newborn does not follow the same feedback mechanisms observed when the thyroid-pituitary axis is fully developed (6). Therefore, the cutoffs for defining severity of ID on the basis of newborn TSH concentrations originally proposed by the WHO have been questioned and are not considered in most of the recent recommendations (3).…”

“…Particularly important is the role of thyroid hormones in normal brain development and cognition. It has been shown that insufficient iodine intake during pregnancy and lactation and in newborns may lead to irreversible brain damage (1)(2)(3)(4)(5)(6)(7)(8)(9). The severity of this impairment varies from cretinism, in regions of severe iodine deficiency (ID), to the inability of children to achieve their potential intelligence quotient, when iodine intake is mildly to moderately insufficient.…”

“…Since 1990 it has been accepted as a basic human right that every child has the right to an adequate supply of iodine to ensure its normal development and that every mother has the right to an adequate iodine nutrition to ensure that her unborn child reaches its potential mental development (4). Further, it is believed that iodine-related neurodevelopmental deficits of future generations can be prevented by promoting universal salt iodination and the use of iodine supplements from the onset of pregnancy or when pregnancy is planned (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Identification of Direct Thyroid Hormone Response Genes Reveals the Earliest Gene Regulation Programs during Frog Metamorphosis

“…This is a critical period of organ growth and maturation, and thus, not surprisingly, T3 deficiency during this period causes severe developmental defects (5,11,12). Interestingly, appropriate levels of maternal T3 are also important to ensure proper mammalian development (13)(14)(15). These observations suggest that proper levels of T3 in both the mother and fetus are critical for mammalian development, which makes it difficult to separate the direct effects of T3 on the development of the fetus versus indirect effects through maternal influence.…”

Drinking water contribution to aggregate perchlorate intake of reproductive-age women in the United States estimated by dietary intake simulation and analysis of urinary excretion data

“…The effect of reduced thyroid function on fetal development appears to be the most severe during the first trimester of pregnancy (Kooistra et al, 2006;Morreal de Escobar et al, 2007). Even relatively modest reductions in thyroid hormone levels in early pregnancy may be associated with adverse effects on fetal nervous system (Pop et al, 1999(Pop et al, , 2003Kooistra et al, 2006).…”