From the Guidelines
Low free T4 levels during pregnancy are most commonly caused by iodine deficiency, and treatment typically involves levothyroxine supplementation to prevent complications such as miscarriage, preeclampsia, and impaired neurological development in the baby. The causes of low free T4 levels in pregnancy can be multifactorial, including:
- Iodine deficiency, as pregnancy increases iodine requirements to support both maternal and fetal thyroid function 1
- Hashimoto's thyroiditis, an autoimmune condition where the body attacks the thyroid gland, which can manifest or worsen during pregnancy
- Pre-existing hypothyroidism that becomes more pronounced when pregnant due to increased metabolic demands
- Certain medications like lithium, amiodarone, or anti-epileptic drugs that can interfere with thyroid hormone production
- Normal physiological changes of pregnancy, including increased blood volume and higher estrogen levels, which can affect thyroid hormone measurements
Maintaining proper thyroid function during pregnancy is crucial, as maternal hypothyroidism can lead to severe complications, including miscarriage, preeclampsia, anemia, postpartum hemorrhage, and impaired neurological development in the baby 1. Treatment with levothyroxine supplementation, with starting doses usually between 1-2 mcg/kg/day, adjusted based on TSH levels every 4-6 weeks, is recommended. Women with known thyroid conditions should have their medication adjusted before conception when possible, and all pregnant women should ensure adequate iodine intake of 250 mcg daily through diet or prenatal vitamins 1.
From the FDA Drug Label
Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentration Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens, and corticosteroids decrease TBG concentration.
The reasons for low free T4 in pregnancy are not directly stated in the label, but it can be inferred that changes in TBG concentration may affect free T4 levels.
- Decreased TBG concentration due to certain conditions such as nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens, and corticosteroids may lead to low total T4 levels, but the free T4 levels may be normal or elevated.
- Increased TBG concentration due to pregnancy, estrogens, or estrogen-containing oral contraceptives may lead to increased total T4 levels, but the free T4 levels may be normal or decreased. However, the label does not provide a direct answer to the question of low free T4 reasons in pregnancy 2.
From the Research
Low Free T4 Reasons in Pregnancy
- Low free T4 (fT4) levels during pregnancy can be caused by various factors, including overt maternal hypothyroidism, which is associated with severely impaired neurological development of the offspring 3.
- Maternal thyroid function during early pregnancy is an important determinant of early fetal brain development, as the fetal thyroid is unable to produce any T4 before 12-14 weeks' gestation 3.
- Low maternal plasma fT4 concentrations during early pregnancy may be an important risk factor for impaired infant development, with children of women with fT4 levels below the 5th and 10th percentiles at 12 weeks' gestation having significantly lower scores on the Bayley Psychomotor Developmental Index (PDI) scale at 10 months of age 3.
- Hypothyroidism in pregnancy, defined as the presence of an elevated thyroid stimulating hormone during gestation, can also lead to low free T4 levels, affecting 2% to 3% of the population 4.
- Free T4 immunoassays may be flawed during pregnancy, with serum free T4 index (FT4I) being a more reliable estimate of free T4 levels than free T4 immunoassays 5.
- Maternal total T4 (TT4) levels are highly variable in the first half of pregnancy and are poorly related to maternal TSH, with no independent association of maternal TT4 with pre-eclampsia, premature delivery, birthweight, or offspring IQ 6.
- The diagnosis and management of thyroid disease in pregnant women are crucial to prevent adverse pregnancy outcomes, with medications that affect the maternal thyroid gland being able to cross the placenta and affect the fetal thyroid gland 7.