The Effects Of Maternal And Umbilical Cord Serum Copper And Selenium Levels On The BMI Developmental Levels Among Infants With 0 Month To 24 Months Old:A Birth Cohort Study

Objective Based on Ma’anshan Birth Cohort Study（MABC）,we aimed to describe the trends of maternal and umbilical cord serum copper and selenium levels;to analyze the affecting factors about the concentrations of two elements during pregnancy;to explore the predictive effect of copper and selenium levels on BMI development levels among infants with 0 month to 24 months old;to reveal the relationship between maternal and umbilical cord serum copper and selenium levels and mRNA expression levels of oxidative stress markers and inflammatory related factors in placentas in order to explain the possible causes of the effects on BMI development levels among infants Methods A prospective birth cohort study design was adopted.The Ma’anshan Birth Cohort Study was established from May 2013 to September 2014 in Ma’anshan Maternal and Child Health Care Hospital.The pregnant women were recruited when they came to this hospital to set up“perinatal health care manual”for the first time,who intended to keep appointments as scheduled and delivered in this hospital.A total of 3474 qualified women were included.The related pregnant women’s information was collected before pregnancy,in early,middle and late pregnancy via face to face interviews,besides,the maternal bloods were collected within a week of interview;the information about the deliveries and newborns was colleted and the fetal umbilical bloodsandplacentaswerecollectedsimultaneously;theinfants’ physical development parameters（height,weight,etc.）were followed up when they were 0,1,3,6,9,12,18,24 months old respectively.Detect the concentrations of two elements in maternal sera in the first,second trimester and umbilical cord sera by ICPMS;the expression levels of 2 oxidative stress markers（HO-1,HIF-1α）and 4inflammatory related factors（IL-1,IL-6,IL-8 and TNF-α）in placentas were detected by RT-PCR;the infants’ weights,body lengths and BMI values were converted to the corresponding age and sex Z scores referring to the standards of child growth and development formulated by WHO in 2006,and the indexes after transformation were WAZ,HAZ and BMIZ respectively.The linear mixed models were used to explore the factors that affect the concentrations of two elements;the nonparametric Friedman tests were used to compare the total concentration differences between the three measured values of the two elements;the non-parametric Wilcoxon tests were used to compare the differences between any two measured values of two elements;the mixed linear models were used to analyze the effects of maternal and umbilical cord serum copper and selenium levels on infants’ BMIZ values with 0 month to 24 months old;after the infants’ BMI developmental trajectory was divided into three sub categories using growth mixture models,the ordinal logistic regressions were used to analyze the effects of serum copper and selenium levels on infants’ BMI classifications with 0month to 24 months old;the mediating effect models were used to analyze the direct effect of cord serum copper levels on postnatal BMI values among infants and the variation tendencies of this effect as they grew older;the multiple linear regressions were used to analyze the associations between serum copper and selenium levels and inflammatory factors and oxidative stress markers of placentas.Results The concentration distributions of copper in maternal sera in the first and second trimester and umbilical cord sera were from 290.05mg/L to 3447.32mg/L,from 528.15mg/L to 4465.30mg/L and from 123.07mg/L to 1845.13mg/L,respectively;the corresponding geometric mean concentrations were 1498.41mg/L,2018.24mg/L and 304.09mg/L,respectively.The concentration distributions of selenium in maternal sera in the first and second trimester and in umbilical cord sera were from 25.77μg/L to 214.32μg/L,from 21.50μg/L to 193.90μg/L and from14.25μg/L to 177.61μg/L,respectively;the corresponding geometric mean concentrations were 71.86μg/L,69.55μg/L and 43.85μg/L,respectively.The intraclass correlation coefficients（ICCs）and their 95%CIs were 0.42（0.38⁰.46）,0.40（0.36⁰.44）respectively.The total concentration differences between three measured values of the two elements and the differences between any two measured values of two elements were all significant.Many factors during pregnancy may affect the concentration distributions of the two elements.The main factors that have great influence on copper levels were pregnant women’s ages,seasons and parities;selenium was mainly influenced by the pregnant women’s education levels and seasons.There were no statistical significances about the effect of maternal serum copper,selenium levels on BMIZ values among infants with 0 month to 24 months old;with umbilical cord serum lnCu levels rising by 1mg/L,the BMIZ values among infants showed a descent trend,theβvalues and their 95%CI in three adjustment models were-0.29（-0.39^-0.19）,-0.26（-0.35^-0.16）and-0.27（-0.35^-0.17）,respectively;in addition,the effect of umbilical cord serum copper levels on BMIZ values among infants showed significant gender difference,theβvalues and their 95%CI in three adjustment models were-0.36（-0.48^-0.23）,-0.24（-0.36^-0.12）and-0.26（-0.39^-0.14）with umbilical cord serum lnCu levels rising by 1mg/L among boys,respectively.With umbilical cord serum lnSe levels rising by 1mg/L,the BMIZ values among infants showed an increased trend,but there was no statistical significance,and theβvalues and their 95%CI in three adjustment models were 0.10（-0.01^-0.21）,0.08（-0.03⁰.19）and 0.08（-0.02⁰.19）.The development trajectory of BMI among infants with 0 month to 24 months old in the cohort could be divided into three categories by using the GMM model.There were no statistical significances about the effect of maternal serum copper,selenium levels on BMI classifications among infants with 0 month to 24 months old.With umbilical cord serum lnCu levels rising by 1mg/L,the ORs and their 95%CIs for the infants tended to classΙ（high BMI group）were 0.50（0.38⁰.67）,0.57（0.42⁰.78）and 0.56（0.41⁰.77）respectively before and after adjusting the confounders,and the same effect appeared only among boys,with umbilical cord serum lnCu levels rising by 1mg/L,the ORs and their95%CIs for the boys tended to classΙ（high BMI group）were 0.36（0.25⁰.53）、0.37（0.24⁰.56）and 0.36（0.24⁰.54）.With umbilical cord serum lnSe levels rising by1mg/L,the ORs and their 95%CIs for the infants tended to classΙ（high BMI group）were 1.26（0.92¹.73）,1.30（0.94¹.80）and 1.29（0.93¹.78）respectively before and after adjusting the confounders,but there were no statistical significances.There were no statistical significances about the effect of the ratio of selenium levels and copper levels in maternal sera on BMIZ values among infants.There were statistical significances about the effect of the ratio of selenium levels and copper levels in umbilical cord sera on BMIZ values among infants with 0 month to 24 months old,with the lnSe/lnCu ratio increasing by 1,theβvalues and their 95%CI in the three adjustment models were 1.66（1.09².23）,1.00（0.47 to 1.52）and 1.01（0.48¹.54）,respectively.There were statistical significances about the effect of the ratio of selenium levels and copper levels in umbilical cord sera on the BMIZ values among boys,with the lnSe/lnCu ratio increasing by 1,theβvalues and their 95%CI in the three adjustment models were 1.76（0.94².59）,1.21（0.48¹.95）and 1.31（0.55².08）,respectively;there was no statistical significances about the effect of the ratio of selenium levels and copper levels in umbilical cord sera on the BMIZ values among girls after adjusting all the confounders,and theβvalues and their 95%CI in three adjustment models were 1.55（0.77².34）,0.95（0.24¹.66）and 0.74（-0.02¹.50）,respectively.There were statistical significances about the effect of the ratio of selenium levels and copper levels in umbilical cord sera on BMIZ classifications among infants with 0 month to 24 months old.Compared with the infants among selenium/copper>P₇₅5 group,the ORs and their 95%CIs for the infants among≤P₂₅group tended to classΙ（high BMI group）were 0.67（0.53⁰.85）,0.72（0.56⁰.92）and 0.72（0.56⁰.61）respectively before and after adjusting the confounders;compared with the infants among selenium/copper>P₇₅5 group,the ORs and their95%CIs for the boys among≤P₂₅5 group tended to classΙ（high BMI group）were 0.53（0.38⁰.74）,0.72（0.56⁰.92）and 0.54（0.38⁰.76）respectively before and after adjusting the confounders and the ORs and their 95%CIs for the boys among P₂₅^P₇₅group tended to classΙ（high BMI group）were 0.62（0.45⁰.84）,0.62（0.45⁰.85）and 0.59（0.43⁰.82）respectively before and after adjusting the confounders.There were no statistical significances about the effect of the ratio of selenium levels and copper levels in umbilical cord sera on the BMIZ classifications among girls with 0month to 24 months old.The mediating effect models demonstrated that umbilical cord serum copper levels had a direct effect on infants’ postnatal BMI development levels,and the weight of this direct effect was basically stable before 9 months old,and then was decreased;besides,this effect was mainly revealed among boys.With umbilical cord serum lnCu levels rising by 1mg/L,the mRNA expression levels of IL-1βand IL-8 in placentas showed an increased trend,theβvalues and their 95%CIs for IL-1βwere 0.30（0.09⁰.51）,0.30（0.08⁰.52）before and after adjusting the confounders and 0.53（0.32⁰.73）and 0.56（0.35⁰.77）for IL-8 before and after adjusting the confounders,respectively.The mRNA expression levels of HO-1 and HIF-1αin placentas showed significant down-regulated trends before and after adjusting confounders with the maternal or umbilical cord serum lnSe levels rising.The ratio of Se/Cu in umbilical cord sera was higher,the mRNA expression levels of IL-6 and IL-8 in boys’ placentas were significantly reduced;the ratio of Se/Cu in umbilical cord sera was higher,the mRNA expression levels of HO-1 and HIF-1αin girls’ placentas were significantly reduced.Conclusion With the increasing gestational age,maternal and umbilical cord serum copper and selenium levels showed a certain trend.There were significant differences between maternal serum levels of two elements in the first and second trimester,besides,the levels of two elements in maternal sera were also significantly different from that in cord sera.Several factors during pregnancy could affect the concentration distributions of two elements.Compared with maternal serum copper and selenium levels,the levels of two elements in umbilical cord sera had more obvious effects on BMI developmental levels among infants with 0 month to 24 months old:as the levels of copper in umbilical cord sera became higher,the risk for infants with lower BMI developmental levels was higher;and this effect was sex-specific,which was only for boys;although umbilical cord serum selenium levels had no significant effect on infants’ BMI developmental levels,the higher ratio of selenium levels and copper levels in umbilical cord sera was helpful to improve infants’ BMI developmental levels.The maternal and umbilical serum selenium levels had a significant antioxidant effect,but the antioxidant effect of selenium has no significant effect on infants’ BMI developmental levels.With umbilical cord serum copper levels increasing,the expression levels of some important inflammatory factors in placentas were significantly up-regulated;with the ratio of selenium levels and copper levels in umbilical cord sera increasing,the expression levels of IL-6 and IL-8 in boys’ placentas showed significant down-regulated trends.Placental inflammation may be an important factor which could affect the fetal growth and development before and after birth,and the specific mechanism needed to be further studied.