Correlation Between Phthalates Exposure And Executive Function Of Preschool Children

ObjectivesPhthalates(phthalic acid esters,PAEs)were a class of synthetic chemicals with endocrine disrupting activity that were widely used in daily work and life.Currently,there were a variety of biological samples can detect the presence of their substances or metabolites,such as serum,urine and nails,suggesting that human exposure to PAEs was widespread,and therefore its toxic effects were attracting more and more attention.Domestic and foreign studies have been shown that the exposure of PAEs can cause various hazards,such as allergic symptoms,reproductive disorders,and neurodevelopmental abnormalities in children’s health.The purpose of this study was to determine the PAEs exposure in preschool children in China by meaxuring the levels of seven PAEs metabolites in preschool children in Ma’anshan city,and to investigate the association between PAEs exposure and preschool children’s executive function.MethodsData for this study were from follow-up data of China-Anhui Birth Cohort Study(C-ABCS).From October 2008 to October 2010,this cohort enrolled pregnant women receiving pregnancy care services from 4 municipal medical and health institutions in Ma’anshan City,Anhui Province,including 5 084 pregnant women and 4 669 singleton live births.This study relies on the seventh follow-up study conducted by C-ABCS from April 2014 to April 2015 for children aged 3 to 6 years.The research team used highperformance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)to detect phthalate metabolites in urine collected from preschool children,such as monomethyl phthalate(MMP),monoethyl phthalate(MEP),monobutyl phthalate(MBP),monobenzyl phthalate(MBzP),mono(2-ethylhexyl)phthalate(MEHP),mono(2-ethyl-5-oxohexyl)phthalate(MEOHP)and mono(2-ethyl-5-hydroxylhexyl)phthalate(MEHHP).We used the Behavior Rating Inventory of Executive Function-Preschool Version(BRIEF-P)collected some relevant sociodemographic information and children’s executive function data,which was completed by parents or major carers.The executive function consists of global executive composite(GEC),inhibitory self-control index(ISCI),cognitive flexibility index(FI)and emergent metacognition index(EMI).After exclusion of follow-up difficulties,poor compliance,suffering from a variety of other serious organic or mental illness and data incomplete children,and ultimately there were 3 725 preschool children aged 3 to 6 years old were included in this study.Statistical description of the concentrations of seven phthalate metabolites concentration in urine of preschool children(mean ± standard deviation,percentiles)and related sociodemographic characteristics.Spearman correlation analyzed the association between urine phthalate metabolites.Univariate logistic regression models were used to analyze the association between different sociodemographic characteristics and children’s executive function.Univariate and multivariate logistic regression models were used to analyze the association between PAEs and children’s executive function.ResultsThis study examined 3 725 preschool children in Ma’anshan City of C-ABCS,there were 46.4%(1 728/3 725)girls,children’s monthly age was mainly ranged from48 to 59 months(2 439/3 725).Children were commonly exposed to phthalates and there was a gender differences.Except for MBzP,the detection rate of PAEs metaboliteswere greater than 99%.The detected concentration of MBP(208.77±200.53 μg/L)was the highest and MBz P(0.51± 8.21 μg/L)was the lowest.Spearman correlation analysis found that phthalate metabolites have a positive correlation and the correlation coefficient(r)ranging from 0.149 ~ 0.962.The metabolites of DEHP(MEHP,MEHHP and MEOHP)had a significant positive correlation(r = 0.738~0.962),and MEHHP and MEOHP had the highest correlation(r= 0.962 / 0.956).The correlation between MBZP and MMP,MEP,MBP were lower with a correlation coefficient of 0.210 ~ 0.375.The correlation between MEHP and MEP,MBP,MBzP were also lower with a correlation coefficient of 0.149~0.347.The correlation between MEOHP and MMP,MEP,MBP,MBzP fluctuated greatly,and the correlation coefficient ranged from 0.236~0.529.Univariate logistic regression analysis of urine PAEs metabolites and executive function of preschool children showed that the risk of ISCI and EMI dysplasia of children occurred in high level of MEHHP were higher than those in low concentration group.The OR(95% CI)values were 1.763(1.150~2.703),1.312(1.027~1.675),respectively.The risk of ISCI dysplasia of preschool children in MEOHP and DEHP high level were increased than those in low concentration group.The OR(95% CI)values were 1.561(1.026 ~ 2.375)and 1.578(1.032 ~ 2.411),respectively,the difference were statistically significant.The covariates included children’s gender and age,maternal and paternal age,parental education level,nature of mother’s work,exposure to second-hand smoke in family,whther children as single child were entered into multivariable logistic regression model.The results showed that the risk of ISCI dysplasia of preschool children in MEOHP,MEHHP and ΣmPAEs high level group were higher than that of the low level group.The OR(95% CI)values were 1.549(1.016 ~ 2.363),1.689(1.096 ~ 2.601),1.592(1.030 ~ 2.460),the difference was statistically significant.ConclusionsPreschool children in Ma’anshan City in Anhui Province are generally exposed to PAEs,and there were a positive correlation between PAEs metabolites.The study found that high levels of PAEs exposure increased the risk of executive function dysplasia of preschool children,demonstrating that PAEs had a detrimental effect on children’s neurodevelopment.