Thyroxine is crucial for normal human brain development in utero and for the first two years after birth. Brain damage through deficiency of T4 is irreversible and the degree and spectrum of subsequent neurodevelopmental disorders is dependent on the timing and severity of T4 deprivation; this presentation will review the current clinical evidence.
Maternal to fetal transfer of thyroxine is essential for the first half of gestation, and to a lesser, and decreasing degree, thereafter. Severe maternal iodine deficiency in pregnancy results in abnormal fetal brain development and neurological cretinism, which is directly related to low maternal T4, and is preventable by iodine supplementation before, or during early pregnancy. Reduced developmental scores in the progeny are also associated with maternal sub-clinical hypothyroidism; the presence of high maternal titres of anti-thyroid peroxidase antibodies during pregnancy, and a maternal FT4 equal to or less than the 10th percentile of first trimester values.
Transient hypothyroxinaemia in preterm infants is common, evident in 41% of infants <28 weeks gestation and in 23% of infants of 2830 weeks gestation. Studies have linked low plasma T4 in preterm infants with later deficits in motor and cognitive function. The aetiology of transient hypothyroxinaemia is not clear and may have contributions from the withdrawal of maternal-placental thyroxine transfer, hypothalamic-pituitary-thyroid immaturity, developmental constraints on the synthesis and peripheral metabolism of iodothyronines, iodine deficiency, and non-thyroidal illness.
Congenital hypothyroidism in term infants if untreated results in severe mental retardation but this is preventable by early and adequate thyroxine therapy; however the outcome may still be less than optimal with subtle intellectual impairments in: visuospatial and visuomotor skills, language, memory abilities, attention, reduced school performance especially arithmetic skills, and mild hearing loss in 20% with associated reading skill problems.
The neonatal thyroid is inordinately sensitive to the inhibitory effect of excess iodine with the development of transient neonatal hypothyroidism. This can follow the application of maternal vaginal povidone-iodine solutions during the last trimester or during labour. Risk factors in the postnatal period are the injection of iodinated contrast dyes to visualise parenteral feeding lines, or the topical application of povidone-iodine solution as a skin disinfectant. These risk factors are more common in preterm than term infants.