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 (T4) for the production of the 3′,3,5-tri-iodothyronine (T3) 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 T4 secreted something that requires a concordant increase in the availability of iodine, from 150 to 250–300 μg I day− 1. Women who are unable to increase their production of T4 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.