A Case-control Study Of Phthalate Exposure And The Susceptibility To Attention Deficit Hyperactivity Disorder In Children Aged 6-12 Years

Objective: To investigate exposure levels of phthalate esters(PAEs)in children aged 6-12 years old,to explore the correlation between the levels of eight kinds of phthalate metabolites in children's urine and the susceptibility to attention deficit hyperactivity disorder(ADHD),and to provide the evidences to prevent of attention deficit hyperactivity disorder in school-aged children.Methods: A case-control study was applied in this study.Childrens aged 6-12 years who was diagnosed with attention deficit hyperactivity disorder in two hospitals in Wuhan from May,2017 to September,2018,were included in case group.Healthy children who was screened by questionnaires in a primary school in Wuhan during the same period were included as the control group.Data were collected by using the self-made child health questionnaire and NICHQ Vanderbilt Assessment Scale—Parent Informant was used to evaluate ADHD symptoms.At the same time,urine samples were collected.The concentration of phthalate metabolites in urine was detected by LC-MS.Mean standard deviation,t test,normality test and Spearman rank correlation were used to describe the data.The statistical correlation was determined by the rates for counting data.The unconditioned univariate or multivariate logistics regression analyzes were used to explore the correlation between ADHD in children and the level of PAEs metabolites in urine.Results: The results of univariate analysis showed that the risk of ADHD in children with high exposure to MMP and MBP was 1.95 times(95%CI: 1.20-3.16)and 9.73 times(95%CI: 5.13-18.44)respectively,than the low exposure.Medium exposure to MBZP and MOP were 2.26 times(95%CI: 1.37-3.73)and 3.55 times(95%CI: 1.84-6.86)more likely to develop ADHD in children than childrens with low exposure.High exposure to MBP was associated with all three subtypes of ADHD(P <0.05),while medium and high exposure to MBZP was only associated with combined subtypes of ADHD(P <0.05).Multivariate analysis showed that,after adjusting for confounders,the risk of ADHD in children with high exposure to MBP and MMP was 4.27 times(95%CI: 1.20-15.17)and 3.52 times(95%CI: 1.24-10.00)than low exposure.High exposure to MMP increased the risk of inattention/hyperactivity subtypes in children(OR=6.14,95%CI: 3.23-14.07).High exposure to MBP was associated with an increased risk of combined subtype ADHD than low-exposure children(OR=2.30,95%CI: 1.54-17.49).Exposure to MEP decreased the risk of ADHD(OR=0.10,95%CI: 0.20-0.44).Conclusions:1.There is a significant correlation between the levels of phthalate metabolites in a single urine sample and ADHD in children.2.After adjusting for confounding factors,high exposure to MBP was a risk factor for children with ADHD and combined subsymptoms of ADHD.3.MMP in the high-exposure level may be associated with the increased risk of the subtypes for attention deficit or hyperactivity disorder in children.