Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimesters) can predict whether their male offspring is aggressive or withdrawn at age 4.
Certain trajectories of maternal thyroid hormones have been associated with problematic behaviors in preschool boys in a study of nearly 2000 mother-child pairs in China.
Most women had a low TSH trajectory and a moderate FT4 trajectory, which the researchers considered to be reference (normal) trajectories.
The primary caregiver (parent or grandparent) completed a detailed questionnaire about their child’s behavior at age 4.
4-year-old boys whose mothers had an elevated TSH trajectory during pregnancy were more likely to be withdrawn and externalize problems (odds ratio [OR]2.01 and 2.69, respectively).
Boys whose mothers had a high TF4 their trajectory during pregnancy were more likely to be anxious/depressed (OR, 2.22).
And boys whose mothers had a moderate TSH or low FT trajectory4 trajectory were more likely to show aggressive behavior (OR, 3.76 and 4.17, respectively) compared to boys whose mothers had normal TSH and FT4 trajectories, after adjusting for potential confounding factors.
However, there was no association between abnormal maternal thyroid hormone trajectories and behavioral 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 and Metabolism.
“Study supports monitoring thyroid function during pregnancy”
“Our results highlight the importance of close monitoring and management of maternal thyroid function during pregnancy,” said lead author Kun Huang, PhD, in an Endocrine Society press release.
“This research presents a new perspective in the early intervention of children’s emotional and behavioral problems,” added Huang, of Anhui Medical University, Hefei, China.
The findings add to a growing body of literature on a controversial link between maternal thyroid hormones during pregnancy, when the fetal brain develops, and later behavior in preschoolers, commented Caroline T. Nguyen. , MD, who was not involved in this research. in an email to Medscape Medical News.
“Some studies show an association between thyroid levels and behavioral outcomes, some do 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 mandate exists for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines recommend screening women at risk for thyroid dysfunction.
“I think screening for thyroid peroxidase (TPOAb) antibody positivity is useful in women who want pregnancy,” Nguyen continued, “because we know that TPOAb-positive patients are at increased risk of miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”
TPOAb positivity is also associated with an increased risk of postpartum and long-term thyroid dysfunction.
This current study, Nguyen summarized, “adds to a growing body of research on the relationship between thyroid hormone levels and neurocognitive outcomes. [in offspring] and supports the monitoring of thyroid disease during pregnancy.”
“However, we do not have enough data to demonstrate the benefits of an intervention with levothyroxine treatment,” she noted.
Nevertheless, the lack of positive data does not suggest that there is no theoretical benefit of the intervention, she said, because such studies are very difficult to perform.
“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‘ Behaviours
Previous studies have reported that during pregnancy, maternal subclinical disorders hypothyroidism (Elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decrease in FT4 with normal TSH) are associated with adverse outcomes for mother and child, including preterm birth and low birth weightLi and his colleagues write.
However, most studies have not determined maternal thyroid hormone levels in different trimesters.
The researchers recruited pregnant women going for their first prenatal checkup at 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 trimesters, on average at the 10th, 25th and 34th week of gestation, respectively.
Researchers found that TSH levels increased somewhat from trimester 1 to trimester 2, then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had an elevated TSH trajectory. .
FT4 levels fell sharply from Trimester 1 to Trimester 2, then increased somewhat in Trimester 3. About half of the women (52%) had moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 path.
Most women (96.5%) had low and stable TPOAb levels, and the rest (3.5%) had high and decreasing TPOAb levels.
When the children in the study were 4 years old, their primary caregiver (parent or grandparent) completed Achenbach’s 100-Question Child Behavior Checklist to determine if the child presented often, sometimes or never three internalizing problematic behaviors (emotionally reactive, anxious/depressed or withdrawn) and/or two externalizing problematic behaviors (attention problems or aggressive behavior).
Limitations of the study, more research is needed
It is unclear why associations between maternal hormones and offspring behavior have only been observed in boys and not in girls. Male fetuses may be more sensitive than female fetuses to changes in maternal thyroid hormone levels during pregnancy, the researchers speculate.
They acknowledge that study limitations include that there were few children with aggressive behavior, so the confidence interval for the association of moderate TSH trajectory with aggressive behavior was very wide.
In addition, caregivers’ assessment of children’s behavior was subjective. Additionally, the researchers did not have information on iodine levels, and low iodine levels can impair brain development in children.
And there may have been residual confounding factors that the researchers did not take into account, such as differences in family upbringing, parental marital status, and 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, University Synergy Innovation Program of Anhui Province, Sci-Tech Basic Resources Research Program of China, National Key Research and Development Program, Academy of Chinese Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. Researchers and Nguyen did not report any relevant financial relationships.
J Clin Endocrinol Metab. Published online January 6, 2022. Abstract