Sex-Specific Effect of Thyroid Peroxidase Antibody and Thyroglobulin Antibody Exposure During Pregnancy on Preschoolers' Emotional and Behavioral Development: A Birth Cohort Study

Background: Epidemiological and experimental studies suggest that thyroid peroxidase antibody (TPOAb)- and thyroglobulin antibody (TGAb)-positive exposure during gestation may contribute to offspring's adverse neural development. However, limited knowledge is available on the association between joint exposure on TPOAb and TGAb and children's emotional and behavioral development. Furthermore, the sex-specific effect on the developmental process of preschoolers' emotions and behaviors is unknown. The present research intends to examine the sex-specific effect of TPOAb- and TGAb-positive exposure in gestation on the developmental process of preschoolers' emotions and behaviors. Methods: A total of 2455 mother-child pairs were included from the Ma'anshan Birth Cohort study. The serum TPOAb and TGAb of pregnant women was measured retrospectively by electrochemical immunoassay during the follow-up period. Preschoolers' emotional and behavioral development was assessed by a child behavior checklist 1.5-5. Growth mixture modeling was adopted to fit thyroid antibody (TAb) trajectories. Poisson regression models were used, stratifying by sex, to examine the association between TAb trajectories, as well as four categories of maternal TAb exposure and preschoolers' emotional and behavioral problems. Results: Boys born to mothers with TPOAb positivity in the first, second, and third trimesters of pregnancy had an increased risk of autism spectrum problems after adjusting for confounders, with relative risk (RR) [confidence interval, CI] of 2.01 [1.24-3.27], 2.15 [1.08-4.26], and 2.13 [1.20-3.79], respectively. Maternal TGAb positivity and TPOAb negativity in the first trimester were associated with a high risk of attention-deficit/hyperactivity problems in boys (RR = 1.74 [CI 1.01-2.99]). The prevalence of depressive problems in girls was 33.3% after exposure to TPOAb alone in the third trimester of pregnancy. Exposure to TPOAb alone in the third trimester of pregnancy was associated with an increased risk of depressive problems in girls (RR = 1.78 [CI 1.09-2.90]). Conclusions: Maternal TPOAb positivity in all three trimesters was associated with the risk of autism spectrum problems in boys. Isolated maternal TGAb positivity in the first trimester was associated with attention-deficit/hyperactivity problems in boys, whereas isolated maternal TPOAb positivity in the third trimester was associated with depressive problems in girls.