上海某社区婴儿邻苯二甲酸酯暴露与神经行为发育的关系

Correlation between phthalates exposure and neurobehavioral development in infants from a community of Shanghai

[目的]邻苯二甲酸酯(PAEs)被广泛应用于塑料等日常生活用品中,在环境中广泛存在且不易降解,造成了食物、水源和空气等生活媒介的普遍污染,其在人群中的暴露水平及潜在健康危害值得关注。婴儿期是人体环境暴露后易于出现不良健康效应的敏感时期。本研究旨在调查哺乳期婴儿PAEs的暴露水平,并探索其与婴儿神经行为发育的关系,为PAEs污染防控和优生优育提供科学依据。[方法]采用前瞻性随访研究设计,于2013年3月至6月对上海154名调查期间处于0～8月龄本市常住人口且健康状况良好的婴儿采集尿样并搜集基本信息,并统一在9月龄的2周内进行年龄与发育进程问卷(ASQ-C)调查,获得婴儿沟通、粗大动作、精细动作、解决问题和个人-社会五大能区的得分情况。通过婴儿家长把尿的方法用一次性尿杯收集尿液,对于年龄过小或不会把尿的婴儿采用集尿袋收集尿液。采用超高效液相色谱-串联质谱法检测尿中PAEs代谢物的质量浓度。使用logistic回归方程对尿中PAEs代谢物浓度与ASQ-C量表结果进行相关分析。[结果]婴儿尿液中PAEs代谢物浓度中位数的前五位依次是邻苯二甲酸单异丁酯(MiBP,35.10 g/L)、邻苯二甲酸单正丁酯(MnBP,34.70 g/L)、邻苯二甲酸单乙酯(MEP,12.15 g/L)、邻苯二甲酸单(2-乙基己基)酯(MEHP,7.85 g/L)和邻苯二甲酸单甲酯(MMP,4.73 g/L);几何均数的前五位的依次是MiBP(30.90 g/L)、MnBP(26.92 g/L)、MEP(11.22 g/L)、单(2-乙基-5-羟基己基)邻苯二甲酸酯(MEHHP,8.13 g/L)和单(2-乙基-5-羧基戊基)邻苯二甲酸酯(MECPP,3.63 g/L)。婴儿沟通能区、解决问题能区、粗大动作能区、精细动作能区、个人-社会能区的平均得分分别为48.54、46.98、51.49、49.06和48.34分。沟通能区与解决问题能区异常率相对较低,分别为11.7%和12.3%;粗大动作能区和精细动作能区异常率相对较高,分别为24.0%和16.9%;而个人-社会能区的异常率则为14.3%。婴儿尿中MEP的质量浓度与粗大动作能区(OR=2.90,95%CI:1.15～7.33)、解决问题能区(OR=5.34,95%CI:1.17～24.44)和个人-社会能区(OR=4.18,95%CI:1.18～14.80)的异常率升高明显相关(P<0.05);此外,婴儿神经行为粗大动作能区的异常率也受MiBP(OR=3.72,95%CI:1.07～12.91)和MEHHP(OR=1.90,95%CI:1.01～14.09)质量浓度的影响(P<0.05)。[结论]哺乳期PAEs(如MEP、MiBP、MEHHP)暴露可能是婴儿神经行为发育的危险因素。

[Objective]Phthalates(PAEs)are widely used in plastics and other daily necessities.Their ubiquitous presence in the environment and high degradation resistance have led to the widespread pollution in food,water,and air;therefore,their exposure levels and potential adverse health effects are concerning.Sensitive periods,such as infancy,are most likely to be affected by PAEs.This study aims to explore the correlation between PAEs exposure and infant neurobehavioral development through the exposure assessment of PAEs in lactating infants,aiming to provide a scientific basis for the prevention and control of PAEs pollution and eugenics.[Methods]Using a prospective follow-up survey design,we collected urine samples and basic information at baseline survey from 154 healthy infants aged 0-8 months in Shanghai from March to June 2013,who had permanent residence in Shanghai.We also evaluated the neurobehavioral development of the infants within 2 weeks of the age of 9 months by the Chinese version of Ages&Stages Questionnaire(ASQ-C),and calculated the score of five individual skills including communication,gross motor,fine motor,problem solving,and personal-social skills.Urine samples were collected either under their parent’s help in disposable cups or with urine collection bags if the babies were too young to pee with parents’help.Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the concentrations of PAEs metabolites in urine.Logistic regression analysis was used to analyze the correlation between urinary concentrations of PAEs metabolites and ASQ-C results.[Results]The top five median concentrations of PAEs metabolites in babies were as follows:monoisobutyl phthalate(MiBP,35.10 g/L),mono-nbutyl phthalate(MnBP,34.70 g/L),monoethyl phthalate(MEP,12.15 g/L),mono-2-ethylhexyl phthalate(MEHP,7.85 g/L),and monomethyl phthalate(MMP,4.73 g/L).The top five geometric mean concentrations of PAEs metabolites were MiBP(30.90 g/L),MnBP(26.92 g/L),MEP(11.22 g/L),MEHP(8.13 g/L),and mono-2-ethyl-5-carboxypentyl phthalate(MECPP,3.63 g/L).The average scores of communication,problem solving,gross motor,fine motor,and personal-social skills were 48.54,46.98,51.49,49.06,and 48.34,respectively.The abnormal rates of communication(11.7%)and problem-solving(12.3%)were relatively low;the abnormal rates of gross motor(24.0%)and fine motor(16.9%)were relatively high;the abnormal rate of personal-social was 14.3%.Infants’urinary concentration of MEP was positively associated with the abnormal rates of gross motor skill(OR=2.90,95%CI:1.15-7.33),problem solving skill(OR=5.34,95%CI:1.17-24.44),and personal-social skill(OR=4.18,95%CI:1.18-14.80)(P<0.05).The abnormal rate of gross motor skill was also positively associated with the urinary concentrations of MiBP(OR=3.72,95%CI:1.07-12.91)and MEHHP(OR=1.90,95%CI:1.01-14.09).[Conclusion]Lactational PAEs exposure such as MEP,MiBP,and MEHHP may be a risk factor of delayed neurobehavioral development in infants.