Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low (P(0)-P(24)), medium (P(25)-P(74)) and high (P(75)-P(100)) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P(25) and P(7)5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times (OR=1.71, 95% CI: 1.11-2.62; OR=1.54, 95% CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times (OR=1.55, 95% CI: 1.00-2.38) than in low concentration group. Conclusion: Phthalates exposure may damage the executive function of preschool children.
目的： 探讨邻苯二甲酸酯（PAEs）内暴露水平与学龄前儿童执行功能之间的关联。 方法： 以2008年10月至2010年10月在安徽省马鞍山市4家市级医疗卫生机构招募的接受孕期保健服务的孕妇作为研究对象，最终有5 084名孕妇及4 669名单胎活产儿进入队列。2014年4月至2015年4月对研究人群进行随访共随访到资料完整的3 725名3~6岁学龄前儿童。研究采用高效液相色谱-串联三重四极杆质谱法（HPLC-MS/MS）同时检测尿液中7种PAEs代谢物，并分别按照其暴露水平以P(0)~P(24)、P(25)~P(74)、P(75)~最大值将调查对象分为低、中、高三组。使用父母填写的《学龄前儿童执行功能量表》（BRIEF-P）调查学龄前儿童执行功能发育情况。应用多因素二分类非条件logistic回归模型分析邻苯二甲酸酯代谢物水平与学龄前儿童执行功能的病因关联。 结果： 学龄前儿童中男童占53.6%（1 997/3 725），儿童月龄为（51.5±5.6）月。7种邻苯二甲酸酯代谢物检出率依次为：邻苯二甲酸单甲酯（MMP）为99.89%（3 721/3 725）；邻苯二甲酸单乙酯（MEP）为99.97%（3 724/3 725）；邻苯二甲酸单苄酯（MBzP）为69.10%（2 574/3 725）；邻苯二甲酸单丁酯（MBP）、邻苯二甲酸-单-（2-乙基-5-酮基己基）酯（MEOHP）、邻苯二甲酸-单-（2-乙基-5-羟基己基）酯（MEHHP）均为100.00%；邻苯二甲酸-单-乙基己基酯（MEHP）为99.95%（3 723/3 725）。上述7种邻苯二甲酸酯代谢物的水平中位数分别为17.71、15.36、0.07、155.24、10.73、14.67、3.59 µg/L。经尿肌酐校正后水平中位数分别为29.65、26.65、0.12、257.73、17.94、24.80、6.27 µg/g肌酐，总PAEs代谢物尿肌酐校正后P(25)、P(75)水平分别为1.20、3.04 µmol/g肌酐。调整儿童性别、月龄、母亲孕龄、父母文化程度、家庭二手烟暴露，儿童是否为独生子女等相关人口学信息后，多因素logistic回归模型结果显示：MEHHP高水平组、MEOHP高水平组学龄前儿童自我抑制控制（ISCI）异常的发生风险分别是低水平组儿童的1.71、1.54倍（OR=1.71, 95%CI: 1.11~2.62；OR=1.54, 95%CI: 1.01~2.34）。总PAEs代谢物高水平组学龄前儿童ISCI异常的发生风险是低水平组儿童的1.55倍（OR=1.55, 95%CI: 1.00~2.38）。 结论： 邻苯二甲酸酯暴露可能损伤学龄前儿童的执行功能发育。.
Keywords: Child, preschool; Cohort studies; Executive function; Exposure; Phthalate.