Hypothyroidism in Pregnancy: Consequences to Neonatal Health

Pregnancy influences thyroid function in multiple ways. Not only does the maternal hypothalamic-pituitary-thyroid (HPT) axis undergo a series of adjustments, the fetus develops its own HPT axis and the placenta plays an active role in iodide and T4 transport and metabolism. Thus, an integrated three-compartment thyroid model exists during gestation (1). Early in pregnancy estrogen promotes production of a more highly sialylated T4-binding globulin isoform that is less rapidly degraded, resulting in increased serum T4-binding globulin and T4 concentrations (1–3). Although a transient decrease in serum free T4, followed by a rise in TSH to a new equilibrium, may occur (3), this is usually not appreciated with routine thyroid testing. A high circulating CG level in the first trimester leads to CG cross-reactivity with the TSH receptor, prompting a temporary increase in free T4 and partial suppression of TSH. The final physiologic change results from placental deiodination of maternal T4, which increases T4 turnover. In normal pregnant women, the thyroid gland maintains euthyroidism with only minor fluctuations in serum T4 and TSH. However, in women with limited thyroid reserve, due to thyroid autoimmunity or iodine deficiency, hypothyroidism can develop (Fig. 1). Fetal thyroid ontogeny begins at 10–12 weeks gestation and is not complete until delivery; T4 is not secreted until 18–20 weeks (1, 3). T4 is critical for many aspects of brain development including neurogenesis, neuronal migration, axon and dendrite formation, myelination, synaptogenesis, and neurotransmitter regulation (4). Although these requirements evolve over months (5), an especially critical time is the second trimester (6). Contrary to past belief, thyroid hormone crosses the placenta. Animal studies have shown that maternal T4 reaches the fetus (5). T4 has been measured in human coelomic fluid as early as 4 weeks gestation (7) and is detectable in cord blood of newborns with athyreosis or thyroid dysgenesis (8). Causes of thyroid dysfunction