Clinical Pearls & Morning Reports
Casey et al. conducted two parallel, placebo-controlled trials to assess the effect of levothyroxine replacement during pregnancy on the IQ of children at 5 years of age who were born to women with subclinical hypothyroidism or hypothyroxinemia, respectively.
What are the specific concerns regarding subclinical maternal thyroid hypofunction during pregnancy?
In 1999, interest in undiagnosed maternal thyroid dysfunction was heightened by studies suggesting an association between subclinical thyroid hypofunction and impaired fetal neuropsychological development. In one report, children of women whose serum thyrotropin levels during pregnancy were greater than the 98th percentile had a lower IQ than children of matched controls who had a normal thyrotropin level. In another study, children whose mothers had a serum free thyroxine (T4) level of less than the 10th percentile in early pregnancy had impaired psychomotor development at 10 months of age, as compared with children whose mothers had a higher free T4 level. Subclinical hypothyroidism has also been associated with increased risks of preterm birth, placental abruption, admission to the intensive care nursery, and other adverse pregnancy outcomes that could explain neurodevelopmental delay.
What do professional organizations currently recommend regarding routine prenatal screening for and treatment of subclinical thyroid disease during pregnancy?
The findings detailed above led several professional organizations to recommend routine prenatal screening for and treatment of subclinical thyroid disease during pregnancy. However, the American College of Obstetricians and Gynecologists has maintained that recommendations for routine screening are premature in the absence of trials showing an improvement in these outcomes with levothyroxine treatment. The Controlled Antenatal Thyroid Screening (CATS) study showed that cognitive function in 3-year-old children was not better than that in controls when mothers who had been identified with subclinical hypothyroidism or hypothyroxinemia were treated with levothyroxine. Despite this evidence, the treatment of subclinical thyroid dysfunction is still recommended by several organizations in their clinical practice guidelines.
Q:Does treatment of subclinical hypothyroidism or hypothyroxinemia during pregnancy have an effect on the cognitive function of children born to such women?
A: The trials by Casey et al. showed no significant effect of thyroid hormone–replacement therapy on the cognitive function of the children or on other indexes of neurodevelopment through 5 years of age. There were no significant differences in measures of behavior, attention deficits, or hyperactivity in either trial. Moreover, treatment of women who had either an elevated thyrotropin level or a low free T4 level had no significant effect on pregnancy or neonatal outcomes.
Q:What study limitation was highlighted by the authors of these two trials?
A: The authors noted that a limitation of the two trials is the relatively late time during gestation at which women were randomly assigned to the trial groups. The fetal thyroid gland begins producing thyroid hormone between 10 weeks and 12 weeks of gestation, and on average, women underwent randomization in the trials by Casey et al. several weeks after this time (at a mean of 16.7 weeks of gestation in mothers with subclinical hypothyroidism and 17.8 weeks of gestation in those with hypothyroxinemia).