BACKGROUND
Adequate thyroid hormone in pregnant women is important for normal development of babies. Low thyroid hormone levels in mothers during pregnancy have been associated with adverse outcomes in children’s brain development, including lower IQ. Autoimmune thyroid disease, with elevated levels of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb), is the most common cause of low thyroid levels in young women in countries with adequate iodine intake. In addition to potentially causing hypothyroidism, elevated thyroid antibodies in the mother during pregnancy have also been associated with higher risks of attention-deficit/ hyperactivity disorder (ADHD) or autism spectrum disorder in the babies in some studies. However, not all studies show similar results and other studies report no such associations. The mechanism of how elevated thyroid antibodies in the mother during pregnancy affect children’s behavioral development is also unclear. Given the lack of clear findings, this study evaluated potential associations between elevated thyroid antibodies in the mother during pregnancy and emotional and behavioral development in preschool-aged children.

THE FULL ARTICLE TITLE
Teng Y et al 2022 Sex-specific effect of thyroid peroxidase antibody and thyroglobulin antibody exposure during pregnancy on preschoolers’ emotional and behavioral development: A birth cohort study. Thyroid 32:1229– 1242. PMID: 35920111.

SUMMARY OF THE STUDY
A total of 2455 Chinese mother-child pairs were included in the study. Mothers were recruited during the first trimester of pregnancy. None of the mothers in the study had history of psychiatric disorder or personal or family history of thyroid disease. Thyroid hormone and thyroid antibody (TPOAb and TgAb) levels were measured in 1824 mothers in the first trimester, 1598 mothers in the second trimester, and 1588 mothers in the third trimester of pregnancy. Mother-child pairs with positive thyroid antibodies (either TPOAb or TgAb) were compared to mother-child pairs with both negative TPOAb and TgAb levels. Children were tested for emotional and behavioral development including stress, depression, anxiety, autism spectrum disorder, ADHD, and oppositional defiant disorder during preschool age through a standardized questionnaire.

Thyroid hormone levels in all mothers were normal during pregnancy. Only a small proportion (3.7%) of mothers with positive thyroid antibodies had high levels, while the majority (96.3%) of mothers with thyroid antibodies had low levels of thyroid antibodies. Boys born to mothers with positive TPOAb in any trimester had about two-fold higher risk of having autism spectrum disorder compared to children born to mothers with negative thyroid antibodies. Boys born to mothers with only positive TgAb (negative TPOAb) in the first trimester had a 1.7-fold higher risk of having ADHD compared to boys born to mother without thyroid antibodies. The degree of thyroid antibody level did not impact the risk of having autism spectrum disorder or ADHD in boys. Elevated thyroid antibody levels in the mother were not associated with other behavioral problems in boys. Risks of autism spectrum disorder or ADHD were not associated with maternal elevated thyroid antibody levels in girls. However, girls born to mothers with positive TPOAb in the third trimester had a 1.7-fold higher risk of having depressive symptoms compared to girls born to mother with negative thyroid antibodies. Depressive symptoms were more common among girls born to mothers with high levels of thyroid antibodies compared to girls born to mothers with low levels of thyroid antibodies.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that elevated thyroid antibody levels in mothers during pregnancy affect emotional and behavioral development in children, but the effect may be different between boys and girls. Maternal TPOAb positivity in all trimesters was associated with a higher risk of autism spectrum disorder in boys. Maternal TgAb positivity in the first trimester was associated with a higher risk of ADHD in boys. Maternal TPOAb positivity in the third trimester was associated with a higher risk of depressive symptoms in girls. This study brings an interesting question regarding the impact of maternal thyroid autoimmunity on children’s brain development, especially their emotional and behavioral development. Currently, we do not fully understand how thyroid antibodies impact children’s brain development unless they cause abnormal thyroid hormone levels. Further studies on the possible mechanism of how thyroid antibodies impact children’s brain development would also be helpful to figure out how to prevent such effect.

— Sun Y. Lee, MD, MSc

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