High, Low Thyroid Hormone Levels During Pregnancy May Affect Fetal Brain Development

SAN DIEGO — Low as well as high maternal thyroid hormone levels during early pregnancy may significantly lower an infant’s IQ later in childhood, according to a new study presented at ENDO 2015.

The study suggests that the common practice of treating pregnant women who have mild thyroid hormone deficiency may pose unexpected risks to the developing baby’s brain.

“Child IQ is a very important marker of cognitive function and is associated with lifetime achievements, various adult diseases, mortality and large economic consequences when decreased. The first associations of maternal thyroid hormone levels with child IQ back in the late 1990s started the development of this field of research and outcomes on IQ are the predominant arguments in international guidelines for treatment recommendation,” said study lead investigator Tim Korevaar, MD, who is a PhD student at Erasmus University in Rotterdam, the Netherlands.

Dr. Korevaar and colleagues evaluated data from 3,839 mother-child pairs who participated in the Dutch Generation R Study. This is an ongoing study examining fetal life through young adulthood.

Between pregnancy weeks 9 and 18, mothers underwent blood work to measure their thyroid-stimulating hormone (TSH) and free T₄. The children to whom the women gave birth underwent an IQ test on nonverbal performance tasks between the age of 5 and 8 years.

The researchers found that the average nonverbal IQ of the children significantly decreased 2.1 to 3.8 points below the average of the reference group (those with free T₄ levels in the middle of the range) when the mothers’ free T₄ level was at or above the 89th percentile (P≤.01). This percentile is considered well into the normal range, according to Dr. Korevaar. The average child IQ decreased by a similar number of points when maternal freeT₄ levels were at or below the eighth percentile (P≤.01), indicating low-normal values.

Percentiles were calculated because different countries and hospitals use different methods to measure free T₄.

Dr. Korevaar said what stands out in this study is that an inverted U-shaped relationship with child IQ level was evident over the entire range of maternal free T₄ levels. Both low and high free T₄ levels were associated with lower child IQ levels. The researchers found no independent association between women’s TSH level and changes in child IQ.

“We do not know what the normal reference range really is and this is currently under debate. This is why we looked at the cut-off values for our effect in percentiles. However, current international guidelines advocate the use of population-based reference ranges, which would make about 3% low and 2.5% high,” said Dr. Korevaar.

Doctors already know that low thyroid hormone levels in pregnant women are linked to lower child IQ scores as well as other risks to the fetus. Based on current evidence, treatment guidelines from the American Thyroid Association in 2011 and the Endocrine Society in 2012 recommend medical treatment of pregnant women with subclinical hypothyroidism. In this mild form of thyroid disease, there is an increased amount of thyroid stimulating hormone (TSH), T₃ and T₄.

“The most important message for endocrinologists is to be careful with supplementation during pregnancy. Commonly, endocrinologists treat until high-normal levels are reached under the notion of it’s better to be safe than sorry. However, we found a detrimental effect already with high-normal levels, which we also recently published for preeclampsia, and there is always residual thyroid stimulation during pregnancy which may increase thyroid hormone levels even further,” Dr. Korevaar told Endocrinology Advisor.

He said there is consensus to treat subclinical hypothyroidism because it is generally believed that the potential benefits of treatment outweigh the potential risks of overtreatment. Nevertheless, until now there was little evidence in humans that high or high-normal elevated levels of thyroid hormone could also be harmful.

Dr. Korevaar said based on European and American surveys the proportion of pregnant women with mild thyroid dysfunction who receive thyroid hormone supplementation is rapidly increasing. Even so, thyroid hormone supplementation during pregnancy may come with the risk for overtreatment, and even treatment to a high-normal level on thyroid function tests early in pregnancy may not be without risks to the child.  He said physicians should keep these new findings in mind and supplement with care.

This is the first study to show that maternal free T₄ levels during early pregnancy are continuously associated with child IQ levels in a U-shape manner, Dr. Korevaar said. In addition, sensitivity analyses indicated that brain development during early life may be affected by maternal free T₄ levels in up to 19% of all children.

Reference

1. Korevaar T et al. Abstract OR11-4. Presented at: The Endocrine Society’s 97th Annual Meeting & Expo (ENDO 2015); March 5-8, 2015; San Diego.