Thyroid function, iodine nutrition and fetal brain development.

Abstract

SUMMARYThe clinical effects of congenital hypothyroidism on brain function have been well documented and the need for early diagnosis and treatment established. This is now possible through neonatal screening. Improved results may be expected but there is evidence of prenatal effects. More evidence of the effects of fetal hypothyroidism on brain development is required in order to determine the need for antenatal diagnosis. Experimental studies indicate significant effects of hypothyroidism on fetal brain development in the monkey and the sheep during the third trimester. In the rat, significant effects, particularly on the cerebellum, can be shown in the first 3 weeks postnatally, a period corresponding to the third trimester of the human pregnancy. Retardation of cerebellar nerve cell migration, differentiation, growth and arborization have all been demonstrated, together with persistence of the external granular zone and DNA polymerase activity. Such effects provide an explanation for the common occurrence of ataxia and nystagmus in congenital hypothyroidism. Severe iodine deficiency with an intake less than 20 μg per day and high goitre prevalence in endemic goitre areas is associated with the condition of endemic cretinism characterised in its fully developed form by mental deficiency, deaf mutism, spastic diplegia and squint with absence of clinical hypothyroidism. This condition does not respond to replacement therapy with thyroid hormones. Correction of the iodine deficiency prior to pregnancy will prevent the condition, but correction of the iodine deficiency in the latter half of pregnancy will not. This indicates the necessity of iodine for fetal brain development in man. Experimental studies in the guinea pig and sheep indicate an effect of severe iodine deficiency on brain growth early in pregnancy at the time of neuroblast multiplication. Such an early effect could provide an explanation for the irreversibility of the effects of severe iodine deficiency on brain development in man. The role of maternal and fetal hypothyroidism and iodine deficiency itself in these effects has still to be defined. It may be concluded that the relation