Subclinical hypothyroidism and hypothyroxinemia during pregnancy have been hypothesized to be associated with cognitive function in offspring. However, recently researchers found that treatment with levothyroxine is not associated with greater IQ in children of mothers who have thyroid disease during pregnancy.
The thyroid is a gland located in the front of the neck right below the Adam’s apple. The main function of this gland is to secrete thyroid hormones (T3 and T4) that have many effects on the human body including regulating the body’s basal metabolic rate and appetite, increased heart rate and body temperature, and among other things, they play a vital role in the maturation of the brain during fetal development. Just like with any other organs of the body, diseases of the thyroid gland can negatively affect its’ function and have widespread damaging results. Over the past 30 years there have been several studies that suggest an association between women who have subclinical thyroid disease during pregnancy and adverse effects in their children.
A recent study published in the New England Journal of Medicine set out to assess the effect of early screening and treatment of women who had been diagnosed with subclinical hypothyroidism or hypothyroxinemia during pregnancy on the IQ of their children at 5 years of age. The researchers, Casey and colleagues defined subclinical hypothyroidism as a thyrotropin (TSH) level >4 mU/L and a normal free thyroxine (T4), and they defined hypothyroxinemia as a normal TSH level and a normal free T4. To analyse both conditions, they conducted two separate trials, both of which included random assignment to either the levothyroxine treatment, or the placebo control group. They screened women with single fetus pregnancies from 15 centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
The study included a total of 677 women with subclinical hypothyroidism (339 were assigned to receive 100mg of levothyroxine daily) and 526 with hypothyroxinemia (265 were assigned to receive 50mg of levothyroxine daily), all having gestational ages between 8-20 weeks. In order to assess the function of the thyroid and the therapeutic level of the levothyroxine (or the placebo), all the women had monthly blood tests to measure their TSH and free T4. To assess the IQ of the children, each child underwent developmental and behavioural testing annually for 5 years. The primary outcome of this study was the full-scale IQ, which was assessed with the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years of age. If the WPPSI-III score was not available, the researchers used the score from the Differential Ability Scales-II (DAS) at age 3.
The results reflected median IQ scores of the children and were compared between those who were treated with levothyroxine and those who were assigned to the placebo group. The researchers report that there were no significant between-group differences in cognitive function, measures of behaviour, attention deficits or hyperactivity in either trial. They did not find that giving thyroid hormone replacement therapy to women with subclinical hypothyroidism or hypothyroxinemia during pregnancy affected the overall cognitive function of their children up until 5 years of age.
One limitation of the study was that women were randomly assigned to either the treatment or the placebo group several weeks after the fetal thyroid gland begins to produce thyroid hormone. This study is important because even though subclinical hypothyroidism has been associated with many obstetrical complications such as increased risk of preterm labour, placental abruption, and admission to the neonatal intensive care unit, there has not been any direct evidence to prove that treatment with levothyroxine would decrease these risks. While other organizations recommend the screening and treatment of subclinical thyroid dysfunction, the American College of Obstetricians and Gynecologists does not recommend routine screening in the absence of trials showing an improvement in these outcomes with levothyroxine.
By: Kimberly Spencer, B. Sc. (Hons)