Clinical Review

Hypothyroidism: Should we screen all pregnant women?

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What are the practical implications of recent studies linking maternal thyroid deficiency with impaired growth, adverse neurologic outcomes, and fetal death?



Emerging research indicates that thyroid hormones play a key role in fetal brain development, and asymptomatic hypothyroidism during pregnancy may have an adverse effect on fetal growth and neurologic development. Findings published in the past year call our attention to the importance of identifying and adequately treating thyroid-deficient gravidas:

  • Maternal free thyroxine (FT4) concentration below the 10th percentile at 12 weeks is associated with significant impairment of psychomotor development at ages 1 and 2 years.1
  • The average serum thyroid-stimulating hormone (TSH) and FT4 levels of neonates born to hypothyroid mothers were significantly higher than those of controls; birth weight and head circumference were significantly lower.2

But given the paucity of data on how maternal hypothyroidism affects the offspring, is universal screening justified? We review the evidence to date, present the current positions of 3 organizations, and offer recommendations for current clinical practice.

Maternal thyroid status is important throughout gestation

The fetal thyroid gland begins to develop at 3 weeks’ gestation; it concentrates iodine and synthesizes thyroid hormone after 10 to 12 weeks.

Prior to this, the mother provides the thyroid hormones through placental diffusion (see “How thyroid needs change during pregnancy”). Indeed, thyroid hormones have been detected in human coelomic and amniotic fluids as early as 8 weeks’ gestation, before the fetal thyroid starts to function.3

New perspective on role of maternal thyroid function. It was previously believed that the mother’s thyroid hormone supply to the fetus was irrelevant after 10 to 12 weeks. However, Vulsma et al4 demonstrated that substantial amounts of thyroxine (T4) are transferred from mother to fetus during late gestation. They discovered T4 in the cord blood of fetuses at term who were unable to synthesize T4 due to organification defects or thyroid agenesis. The T4 in these cases (noted at concentrations 25% to 50% of normal) was obviously of maternal origin.

How thyroid hormone needs change during pregnancy

Thyroid hormone requirement increases during pregnancy in normal women, to provide for the added maternal and fetal needs. Thyroxine (T4) requirement also may grow as a result of placental degradation and increased maternal T4 clearance.20

Thyroid hormone turnover is altered during pregnancy, mainly in association with:

  • lowered iodide availability to the maternal thyroid gland,
  • increased serum thyroid-binding globulin (TBG) concentration, and
  • increased production of thyroid-stimulating factors by the placenta.
  • Maternal serum inorganic iodide levels decrease during pregnancy, possibly due to increased renal clearance of iodide—which stems from increased glomerular filtration rate, and transplacental transfer of iodide and iodothyronines.8,21 The reduced circulating concentration of iodide leads to decreased availability of iodide to the thyroid gland, and results in a 10% to 20% increase of thyroid volume.21 This iodide loss has no clinical importance where iodine intake is sufficient, but may lead to hypothyroidism and goiter in regions of overt iodine deficiency.
  • The increase in the TBG serum concentration in pregnancy results from estrogen-induced increased synthesis and reduced hepatic clearance of TBG.

Most pregnant women are euthyroid by laboratory evaluation, and their TSH, free T4, and free T3 levels remain within normal values.

Thyroid hormones: Important to brain differentiation and development

In the mammalian embryo, thyroid hormones appear to regulate processes of neuronal proliferation, migration, synaptogenesis and myelination, though the precise mechanism is not fully understood.

Unlike T4, triiodothyronine (T3, the most potent thyroid hormone) does not readily penetrate the brain. Indeed, most brain T3 is produced locally from T4, after which it binds to nuclear thyroid hormone receptors. These in turn bind to specific DNA sequences in the regulatory region of target genes.5 A sufficient level of such receptors has been observed in the human fetus as early as 9 weeks’ gestation.

Information comes mostly from animal models, mainly rats. We must thus remain aware that the transfer of thyroid hormones from mother to embryo or fetus may differ between species,6 as may the stages of brain development before and after birth.

Hypothyroidism during pregnancy

The frequency of thyroid deficiency in pregnancy varies from 0.19% in Japan7 to 2.2% in Belgium8 and 2.5% in the United States.9

Hypothyroidism in pregnancy may be due to preexisting illness or a disease that evolves during pregnancy; in developed nations, the most common causes are Hashimoto’s thyroiditis, subacute thyroiditis, and surgical or radioactive ablation of the thyroid gland.

The hypothyroid state may be subclinical and can remain undiagnosed throughout pregnancy. The clinical manifestations of hypothyroidism (fatigue, sensitivity to cold, muscle irritability, cramps, constipation, paresthesia of the distal portion of the extremities, dry skin, and hair loss) may be masked in gestation as symptoms of pregnancy. Gestational hypothyroidism can be classified as overt (low FT4 values and elevated TSH) or subclinical (normal FT4 values and elevated TSH).

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