Pregnant women with subclinical hypothyroidism or hypothyroxinemia received thyroid hormone supplementation or placebo. Compared to placebo, thyroid hormone did not improve children’s cognition at age five. Although results are negative, the study is incomplete for two reasons:
- Levothyroxine was not initiated until week 17 of gestation. For more meaningful results, thyroid hormone should be started before pregnancy or very early in the first trimester.
- Longer follow up of 10-15 years would be more appropriate in evaluating children’s cognition and IQ scores.
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N E J M
Randomized Trial
March 2017
Background
Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring.
It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children.
Methods
We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a high TSH>4.00 and a normal FT4 0.86-1.90 ng/dL, and for hypothyroxinemia, defined as a normal TSH level 0.08-3.99 and a low free T4 <0.86 ng/dL.
In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo.
Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years.
Results
A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation.
- In the subclinical hypothyroidism trial, the median IQ score of the children was 97 in the levothyroxine group and 94 in the placebo group (P=0.71).
- In the hypothyroxinemia trial, the median IQ score was 94 in the levothyroxine group and 91 in the placebo group (P=0.30).
- In each trial, IQ scores were missing for 4% of the children.
- There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups.
Conclusions
Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8-20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions.