The IQ scores of children of hypothyroid women averaged 4 points lower than those of controls at age 7 to 9 years.
Increased rates of fetal death have also been associated with subclinical disorder (see “The importance of adequate supplementation: 2 case studies”).10
Monitoring thyroid hormone levels in hypothyroid women is performed several times during gestation (every 4 to 6 weeks), and the dosage of T4 supplementation adjusted as needed. Mandel et al, who studied women with primary hypothyroidism, noted that the replacement dosage had to be increased by 45% during pregnancy.11 This trend was apparent in the first trimester and persisted throughout gestation.
The importance of adequate supplementation: 2 case studies
The following cases underscore the importance of:
- knowledge of maternal thyroid status during periconception,
- thyroid hormone supplementation for subclinical hypothyroidism, and
- close follow-up and appropriate adjustment of replacement therapy throughout pregnancy.
Case 1
Elevated TSH discovered after successive pregnancy losses
A woman suffered 2 consecutive pregnancy losses. Subsequent work-up revealed subclinical hypothyroidism: Her thyroid-stimulating hormone (TSH) value was moderately elevated and free thyroxine (FT4) was normal. Thyroid hormone supplementation was initiated.
Four months later the patient conceived spontaneously. Levothyroxine therapy in the prepregnant dosage was continued. The mother’s general physician monitored her levels during gestation.
TSH value was normal at 5 weeks but elevated again at 9 weeks. The dosage of thyroid hormone supplementation was increased and the TSH value returned to normal—and remained so in all subsequent studies, every 4 to 6 weeks until labor.
The child was born at 40 weeks’ gestation, with a birth weight of 3,680 g, a head circumference of 36 cm, and normal neonatal thyroid functions. Presently 7 years old, he is healthy and well developed.
Case 2
The perils of unmonitored supplementation
A year after her thyroid function was found to be normal, a woman became pregnant. At the 5th gestational week, fatigue and constipation prompted reexamination of her thyroid function. TSH values were elevated; FT4 was borderline low.
According to her endocrinologist she was given levothyroxine 100 μg daily throughout pregnancy, but no follow-up was conducted. At 39 weeks’ gestation the patient delivered a male newborn weighing 2,890 g with a head circumference of 33.7 cm. Neonatal thyroid function was:
- at 52 hours of age, TSH = 14.3 μIU/mL, FT4 = 37.4 pmol/L;
- at 132 hours of age, TSH = 8.0 μIU/mL, FT4 = 31.5 pmol/L.
Spontaneous normalization of the pituitary-thyroid axis was evident at age 17 days. The child, now 9 years old, displays problems with fine motor coordination and mild learning impairment.
How does maternal thyroid status affect fetal brain development?
Data on the impact of maternal hypothyroidism on the offspring’s mental development come from interventional experimental studies in animals, and, in humans, from observational studies only.
Animal studies show permanent cortical changes. Hypothyroidism in rats causes a reduction in brain size of the newborn pups and a lower total body mass of the embryos.12
Lavado-Autric et al13 recently reported that subtle T4 insufficiency in the pregnant rat disrupts migration of neurons in the fetal cortex and hippocampus, leading to the presence of neurons in aberrant locations in the adult offspring’s brain and “blurring” of cortical layers. These alterations in cortical cytoarchitecture seem to be permanent, not simply a reflection of delayed maturation.
Recent human studies point to neurologic impairment. It is well recognized that severe iodine deficiency during pregnancy may be associated with impaired psycho-neuro-intellectual outcome in progeny. However, since thyroid hormone deficiency can occur in both mother and fetus, it is difficultto determine whether any mental retardation is caused by maternal or fetal hypothyroidism, or both.
- Elevated maternal TSH associated with lower child IQ scores. Man and Jones14 first suggested in 1969 that mild maternal hypothyroidism with no iodine deficiency was associated with lower infant IQ scores.
- First trimester hypothyroidism linked to impaired psychomotor development. A 2003 study by Pop et al1 investigated the relationship between maternal hypothyroxinemia in the first trimester and neurodevelopment of the offspring. They showed that low maternal FT4 (below the 10th percentile) with normal TSH at 12 weeks’ gestation was associated with significant impairment of the child’s psychomotor development at 1 and 2 years of age.
- Alterations in the pituitary-thyroid axis noted in the early neonatal period. Recently, we prospectively compared thyroid function in 2 groups of full-term newborns: 259 infants born to 250 hypothyroid mothers who received thyroid replacement therapy during pregnancy, and 139 healthy newborns of women who had at least 2 normal thyroid function tests during their pregnancy.2 Maternal thyroid function tests were assessed 2.3±0.7 (mean±standard deviation) times during pregnancy.
Official guidelines are unclear