The Role Of Inflammation Markers In The Association Between Excessive Gestational Weight Gain And Social-emotional Status In Children: A Birth Cohort Study

Objectives The purpose of this study is to elucidate trajectories of gestational weight gain and the distribution of inflammatory markers during pregnancy,which explores the relationship among the rate of gestational weight gain,inflammation markers and social-emotional development.And to reveal the mediating significance of maternal and fetal inflammation in the relationship mentioned above,therefor to provide a clue for the fetal origin and biological mechanism of neurodevelopmental disorders in children.Method The baseline survey was based on the Ma'anshan Birth Cohort?MABC?cohort of 3,474 pregnant women.To fill out?the Maternal and Child Health Record Form?at the first prenatal examination.Maternal height,weight and blood pressure,fasting blood glucose values were measured at the first,second and third trimesters of pregnancy,and the glucose tolerance experiment was measured in the second trimester of pregnancy.Serum inflammatory markers were detected by Multi-bead enzyme-free analyzer MILLIPLEX ? MAP instrument,including IFN-??IL-1??IL-6?IL-8?IL-10?IL-12p70?IL-17A?TNF-?.18 months old children social-emotional development were evaluated by Ages and Stages Questionnaires: Social-Emotional?ASQ: SE?.A linear spline regression model was used to describe the trajectories of gestational weight gain.The distribution of inflammation markers during pregnancy was described by geometric mean,mean? ???± s?,P₂₅?P₅₀?P₇₅,minimum value,maximum value.The intraclass correlation coefficient?ICC?was used to test the relationship between 8 inflammation markers during pregnancy.Correlation heatmap was for comparison among inflammatory markers.?² test or t test was used for describing the risk factors of Log conversion of inflammatory markers value,rate of gestational weight gain,inflammation markers during pregnancy and social-emotional development.The DAGitty tool was used to describe relationships among control variables.Multiple logistic regressions models were used to analyze relationships among gestational weight gain,inflammation markers during pregnancy and social-emotional disorders.The linear mixed model was used to analyze the association between gestational weight gain and inflammation markers in pregnant women and fetus.The multi-classification mediation model was used to analyze mediating effects.Examining mediating effectiveness were by the R software of RMediation package.Results Trajectories of the rate of weight gain during pregnancy showed that with the lowest rate in the first trimester?0.16 kg/w;95% CI: 0.14-0.17 kg/w?,with the faster rate in the second?0.57 kg/w;95% CI: 0.56-0.58 kg/w?and third trimesters?0.62 kg/w;95% CI: 0.61-0.63 kg/w?.Rate of gestational weight gain was started to accelerate from the 12 th weeks during pregnancy.The pre-pregnancy obesity women had a slower rate of gestational weight gain compared with women in the other pre-pregnancy BMI categories.There was a significant difference among trajectories of women with pre-pregnancy BMI categories?P value <0.05?.The higher whole gestational weight gain could increase risk of social-emotional disorders.Higher rate of gestational weight gain in the first trimester was a protective factor of social-emotional development.While higher rate of gestational weight gain in the second and third trimesters both increased the risk of social-emotional disorders.After controlling the demographic information,higher whole rate of gestational weight gain and rate of gestational weight gain in the third trimester still increased the risk of social-emotional disorders.Gender stratification showed that girls were more sensitive to the risk of social-emotional disorders.The highest concentration of 8 inflammatory markers were in the third trimester.Compared with other 7 inflammatory markers,TNF-? level was highest in the cord serum.Intraclass correlation coefficient of IL-6,IL-12p70 and IL-17 A were 0.43,0.42 and 0.42,respectively,showed relatively small variability during pregnancy.After controlling for some confounders,rate of gestational weight gain had a positive association with pregnant women serum levels of IFN-?,IL-1?,IL-6,IL-12p70,IL-17 A,TNF-? and cord serum level of IL-10.Each 1 kg per week increased in rate of gestational weight gain was associated with 0.33?95%CI: 0.16-0.50?pg/m L higher serum IFN-?,0.21?95%CI: 0.05-0.38?pg/m L higher IL-12p70,0.23?95%CI: 0.03-0.42?pg/m L higher IL-17 A,0.27?95%CI: 0.10-0.45?pg/m L higher TNF-? and 0.31?95%CI : ?0.57-?0.05?pg/m L lower IL-8.Serum IFN-? in the first trimester,TNF-? in the second trimester and IL-6 in the cord increased the risk of social-emotional disorders.Higher IL-8 level in the second trimester reduced the risk of social-emotional disorders.After controlling confounding factors,IFN-? played a positive mediating role in the relationship between rate of gestational weight gain and social-emotional disorders.The mediating effect ratio was 25.04%.Conclusions Gestational weight gain trajectories of pregnant women change from 12 weeks begin to increase rate of gestational weight gain,20-30 weeks growth faster.Pre-pregnancy BMI is negatively associated with weight gain during pregnancy,and excessive gestational weight gain may lead to immune activation during pregnancy.High gestational weight gain increases the risk of social-emotional disorders in 18 months old children,especially girls more sensitive.The trajectories of 8 inflammation markers levels during pregnancy increase in the third trimester.Changes in the inflammatory environment during pregnancy due to weight gain during pregnancy mainly in the maternal,not in the cord blood.IFN-? levels during pregnancy can mediate the relationship between excessive gestational weight gain and children's psychological and behavioral development.