Sex-specific Effects Of Maternal Thyroid Peroxidase Antibody Exposure On Children’s Emotional And Behavioral Development:A Birth Cohort Study

ObjectivesWe aims to examine the association between maternal thyroid peroxidase antibody（TPOAb）and preschool children’s emotional and behavioral problems,gender differences and the potential critical period.MethodsBased on the Ma’anshan Birth Cohort in China,a total of 3474 pregnant women who underwent the first prenatal examination in Ma’anshan Maternal and Child Health Center from May 2013 to September 2014 were recruited.In accordance with the inclusion and exclusion criteria,2464 singleton live birth mother-child pairs were finally included in this study for data analysis.Basic demographic characteristics of the participants were collected using questionnaire survey,and the information related to the mother and baby at the time of delivery was abstracted from medical notes.The fasting venous blood was collected from pregnant women at different gestation periods.The centrifuged sera were stored at-80°C.Maternal thyroid function indicators,including maternal TPO,TSH and FT₄concentrations were measured retrospectively using electrochemiluminescence immunoassay（ECLIA）during offspring’s follow-up.The Strengths and Difficulties Questionnaire was used to evaluate the emotional and behavioral problems of preschool children.Epi Data3.0 was used to establish a database and SPSS 23.0 was adopted for data analysis.Mplus7.0 software was introduced to fit the trajectories of maternal TPOAb.Binary logistic regression models were used to observe the associations of different trajectories of maternal TPOAb and children’s emotional and behavioral problems.The effects of TPOAb exposure in isolated trimester of pregnancy on children’s emotional and behavioral development were examined stratified by gender.Multiple sensitivity analyses were performed to rule out the chance findings.ResultsAccording to the best model fitting indicators and clinical significance,two trajectories of maternal TPOAb were obtained:the relatively high level group（3.7%）and the relatively low level group（96.3%）.With the progress of pregnancy,maternal TPOAb level displayed a decreasing tendency.After adjusting for potential confounding factors,girls born from mothers with high maternal TPOAb trajectory had a higher risk of conduct problems than those whose mothers had low TPOAb trajectory,with an OR and 95%CI of 2.670（1.040,6.852）.Key period analyses revealed that maternal TPOAb exposure in the first trimester was associated with an increased risk of conduct problems in children,with OR and 95%CI of 1.845（1.067,3.189）.Maternal TPOAb exposure in the third trimester of pregnancy was associated with an increased risk of emotional symptoms in children,with an OR and 95%CI of 1.964（1.117,3.453）.When stratifying by sex,it was found that maternal TPOAb exposure in the third trimester of pregnancy was associated with emotional symptoms in boys,with an OR and 95%CI of 2.510（1.058,5.954）.This association did not exist after further adjusting for exclusive breastfeeding within 6 months after delivery.ConclusionsIn the relatively during pregnancy,girls had a higher risk of conduct problems who born of mothers with high trajectory of maternal TPOAb than those whose mothers had low maternal TPOAb.Maternal TPOAb exposure in the third trimester of pregnancy was related to the increased risk of boy’s emotional problems,and this association was mediated by exclusive breastfeeding within 6 months.