Medical Technology

Preschool Boys' Behaviors Traced Back to Moms' Thyroid Hormones

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2000 mother–child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

Most women had a low TSH trajectory and moderate FT4 trajectory, which the researchers deemed to be reference (normal) trajectories.  

The children’s primary caregiver (parent or grandparent) completed an extensive questionnaire about their child’s behavior at age 4.

The 4-year-old boys whose mothers had a high TSH trajectory during pregnancy were more likely to be withdrawn and to externalize problems (odds ratio [OR], 2.01 and 2.69, respectively).

Boys whose mothers had a high FT4 trajectory during pregnancy were more likely to be anxious/depressed (OR, 2.22).

And boys whose mothers had a moderate TSH trajectory or low FT4 trajectory were more likely to show aggressive behavior (OR, 3.76 and 4.17, respectively) compared with boys whose mothers had normal TSH and FT4 trajectories, after adjusting for potential confounders.

However, there was no association between abnormal maternal thyroid hormone trajectories and behavior problems in 4-year-old girls.

The study by Peixuan Li, BM, and colleagues was published online January 6 in the Journal of Clinical Endocrinology & Metabolism.

Study Supports Monitoring Thyroid Function in Pregnancy

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Huang, from Anhui Medical University, in Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email to Medscape Medical News.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Nguyen.

Maternal TSH and FT4 Trajectories and Preschoolers Behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight, Li and colleagues write.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1860 mother–child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester, at on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).

Study Limitations, More Research Needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys and not girls. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Nguyen have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online January 6, 2022. Abstract  

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