Abnormal thyroid hormones during pregnancy linked to behavioral problems in boys
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Abnormal thyroid hormone levels during pregnancy are associated with an increased risk for behavioral problems in preschool-aged boys, but not girls, according to study data published in The Journal of Clinical Endocrinology & Metabolism.
“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” Kun Huang, PhD, of the department of maternal, child and adolescent health at Anhui Medical University School of Public Health in China, said in a press release. “This research presents a new perspective in early intervention of children's emotional and behavioral problems.”
Researchers recruited 1,860 pregnant women who had their first antenatal checkup at Ma’Anshan Maternal and Child Health Hospital in China from May 2013 to September 2014. All participants were within 14 weeks of pregnancy at their first checkup, had no mental illness and were willing to participate in follow-up of their children. Blood samples were collected during each trimester of pregnancy to measure thyroid hormones. Women were placed into a high-, moderate- or low-level group for thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies based on trajectories during pregnancy. At the child’s mean age of 4 years, caregivers completed the Achenbach Child Behavior Checklist to assess behavioral problems. The checklist included three summary scales: internalizing problems, externalizing problems and total problems. Internalizing problems included emotional reactiveness, anxiety/depression and withdrawal. Externalizing problems included attention problems and aggressive behavior.
Of the participants, 67.8% had a low TSH level, 27.8% had a moderate level and 4.4% had a high level. For free T4, 33% of the women had a low level, 52.4% had a moderate level and 14.6% had a high level. Maternal thyroid peroxidase antibodies were low and stable for 96.5% of participants and high and decreasing for 3.5%.
For preschool-aged boys, the prevalence of externalizing behavioral problems was highest for those with mothers in the high TSH group and lowest in those with mothers in the low TSH group. Anxious/depressed feelings were highest for boys with mothers in the high free T4 group and lowest in boys with mothers in the moderate free T4 group.
After adjusting for confounders, maternal high TSH was associated with an increased likelihood for withdrawal (adjusted OR = 2.01; 95% CI, 1.16-3.5) and externalizing problems (aOR = 2.69; 95% CI, 1.22-5.92) in boys. Moderate TSH during pregnancy was associated with increased odds for aggressive behavior in boys (aOR = 3.76; 95% CI, 1.16-12.23). High free T4 during pregnancy increased the odds for anxious/depressed feelings (aOR = 2.22; 95% CI, 1.08-4.56) and total problems in boys (aOR = 1.74; 95% CI, 1.13-2.66), whereas low free T4 was associated with increased aggressive behavior in boys (aOR = 4.17; 95% CI, 1.22-14.24). There were no associations observed between maternal thyroid hormone levels and emotional or behavioral problems for girls.
The researchers said it is unknown why maternal thyroid hormones are associated with behavior changes in boys and not in girls, but there is evidence that the interaction between thyroid hormones and sex steroid hormones may be more direct in boys.
“Thyroid hormones are reported to be associated with testicular development, growth and maturation,” the researchers wrote. “They will enhance gonadotropin-induced androgen synthesis and release in the testis. Experimental studies indicated that thyroid hormone is essential for male’s typical brain development. We suspect that boys may be more susceptible to alterations of maternal thyroid hormones and thus further to the subsequent behavioral problems.”
Perspective
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In their recent publication, Li and colleagues demonstrate a sex-specific association between maternal thyroid hormone levels throughout pregnancy and offspring’s behavioral development at age 4 years old. The study was ambitious with a large cohort followed over several years. The study is novel in that the investigators measured thyroid function tests in each trimester of pregnancy rather than a single measurement as in the case with the majority of prior studies. The study also stratified for children’s sex allowing for the examination of a sex-specific association of thyroid hormone and behavioral development.
The findings add to a controversial and inconsistent growing body of literature evaluating maternal thyroid hormone levels during pregnancy and neurocognitive outcomes. While the findings are intriguing and support the notion of fetal programming, their clinical significance remain unclear. What is challenging about such studies is that while potential confounders are adjusted for, behavioral assessments are completed by caregivers and subjective. The authors also noted that the study does not take into account factors such as iodine status, family environment and environmental exposures.
The study nicely demonstrates thyroid hormone trajectories in a large cohort of patients. As expected, the majority of patients had “low” TSH trajectory throughout pregnancy and free T4 was highest in the first trimester, declining in the second trimester. The study raises questions of the role of sex in thyroid hormone levels and neurocognitive development and whether intervention with levothyroxine would affect outcomes.
In conclusion, the results of this study support the importance of preconception counseling for patients who are interested in pregnancy with appropriate screening, diagnosis and treatment of thyroid dysfunction prior to conception.
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