In a new randomized trial from Lazarus and colleagues, antenatal screening (at a median gestational age of 12 weeks 3 days) and treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age.
High levels of thyrotropin in women during pregnancy have been associated with impaired cognitive development in their offspring. This finding suggests that antenatal screening and treatment of thyroid deficiency may be worthwhile.
• At what point in gestation does the fetus begin to secrete thyroid hormone?
Active secretion of thyroid hormone in the fetus does not start until about 18 to 20 weeks’ gestation. Studies in animals suggest that until fetal hormone secretion begins, the fetus is dependent on maternal circulating free thyroxine (free T4) for growth and development, including central nervous system maturation. Iodine is essential for free T4 synthesis, and in iodine-deficient populations, an increase in cognitive performance has been observed after iodine supplementation before pregnancy.
• Is there a benefit in childhood cognitive function when antenatal hypothyroid screening is performed in women under 20 weeks’ gestation?
In a study by Lazarus et al. in this week’s issue of the Journal, maternal screening at a median gestational age of 12 weeks 3 days and treatment of hypothyroidism did not result in improved cognitive function in offspring at 3 years of age. The mean standardized IQ in children in the control group was 100.0 (by definition) as compared to 99.2 in the screening group (P=0.40). The proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (P=0.39). An analysis adjusting for initial thyrotropin measurements (log-transformed) did not show a significant association between thyrotropin and IQ and yielded results that were not materially different.
Table 2. Standardized Full-Scale Child IQ and Scores on the Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function, Preschool Version (Brief-P), According to Study Group.
Morning Report Questions
Q: How do the authors explain the difference between their outcomes and the outcomes of prior observational studies?
A: Prior observational studies have shown associations between low maternal thyroid hormone levels in pregnancy and impaired cognitive development in children. A study in 1971 described impaired intellectual development in children born to women with non-iodine-deficient hypothyroidism during pregnancy. A subsequent study showed an IQ level of less than 85 in 19% of the children of women with a high thyrotropin level, as compared with 5% of the children of euthyroid women in the control group. The authors assert that these observational studies may have been confounded. They also indicate that there may be more specific cognitive impairments associated with maternal hypothyroidism that were not assessed in their study, which predominantly assessed IQ. They note two other possible explanations for the negative results of the study. First, that screening was performed and levothyroxine therapy initiated too late in gestation (median, 13 weeks 3 days) to have a major influence on brain development, and second, that it is also possible that IQ assessment at 3 years of age is insensitive to the effects of maternal levothyroxine treatment. A study by Haddow et al. showed an association between hypothyroidism in women and a lower IQ in their children in which psychological testing was performed at 7 years.
Q: What are the current guidelines for antenatal hypothyroidism screening?
A: Current guidelines do not recommend routine antenatal screening for hypothyroidism in pregnancy. This study provides support for these guidelines, since the authors found no benefit of routine screening for maternal hypothyroidism at about 12 to 13 weeks’ gestation in the prevention of impaired childhood cognitive function.