背景:内分泌干扰化学物质(EDC)是广泛使用的化合物,具有影响儿童神经发育结果的潜力,包括自闭症谱系障碍(ASD)。我们的目的是检查尿液中EDC生物标志物的浓度,包括邻苯二甲酸酯,酚类物质,和对羟基苯甲酸酯,并调查婴儿期早期暴露是否与后期ASD或其他非典型发育(Non-TD)或不良认知发育的风险增加相关。
方法:这项分析包括来自婴儿学习早期体征(MARBLES)研究中自闭症风险标志物的婴儿,高危ASD队列(n=148;对应于188个尿液样本)。对3个月和/或6个月大的婴儿的尿中的32个EDC生物标志物进行定量。使用最小二乘几何平均值计算EDC生物标志物浓度的趋势。36个月大的时候,儿童被临床分类为患有ASD(n=36),非典型发展(非TD;n=18),或通过临床评估的典型发展(TD;n=81)。三项逻辑回归分析用于测试生物标志物与ASD之间的关联,或非TD,与TD儿童相比。在单一分析物分析中,在4个评估时间点(6,12,24和36月龄),使用Mullen早期学习量表(MSEL),使用广义估计方程研究了每种EDC生物标志物与认知发展纵向变化之间的关联.此外,分位数g计算用于测试混合效应。
结果:EDC生物标志物浓度在研究期间普遍下降,除了对苯二甲酸单-2-乙基-5-羧基戊基酯。总的来说,3和/或6月龄EDC生物标志物与ASD或非TD风险增加无关。一些显示出显著的逆关联。然而,在评估四个评估时间点的MSEL分数的纵向变化时,邻苯二甲酸单乙酯(MEP)升高与复合评分(β=-0.16,95%CI:0.31,-0.02)和精细运动技能分量表(β=-0.09,95CI:0.17,0.00)的评分降低显着相关,和视觉接收(β=-0.11,95%CI:0.23,0.01)。此外,对苯二甲酸二(2-乙基己基)酯(DEHTP)的代谢物总和与较差的视觉接收有关(β=-0.09,95%CI:0.16,-0.02),综合评分降低(β=-0.11,95%CI:0.21,-0.01)。使用分位数g计算分析的混合物分析未显示EDC生物标志物的混合物与MSEL子量表或复合评分之间的显著关联。
结论:这些发现强调了婴儿暴露对认知发育的潜在重要性。未来的研究可以帮助进一步调查早期婴儿暴露是否与长期缺陷有关,并特别注意随时间趋势增加的EDC,以及它们是否可能对神经发育产生不利影响。
BACKGROUND: Endocrine disrupting chemicals (EDCs) are widely used compounds with the potential to affect child neurodevelopmental outcomes including autism spectrum disorders (ASD). We aimed to examine the urinary concentrations of biomarkers of EDCs, including phthalates, phenols, and parabens, and investigate whether exposure during early infancy was associated with increased risk of later ASD or other non-typical development (Non-TD) or adverse cognitive development.
METHODS: This analysis included infants from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) study, a high-risk ASD cohort (n = 148; corresponding to 188 urine samples). Thirty-two EDC biomarkers were quantified in urine among infants 3 and/or 6 months of age. Trends in EDC biomarker concentrations were calculated using least square geometric means. At 36 months of age, children were clinically classified as having ASD (n = 36), nontypical development (Non-TD; n = 18), or typical development (TD; n = 81) through a clinical evaluation. Trinomial logistic regression analysis was used to test the associations between biomarkers with ASD, or Non-TD, as compared to children with TD. In single analyte analysis, generalized estimating equations were used to investigate the association between each EDC biomarkers and longitudinal changes in cognitive development using the Mullen Scales of Early Learning (MSEL) over the four assessment time points (6, 12, 24, and 36 months of age). Additionally, quantile g-computation was used to test for a mixture effect.
RESULTS: EDC biomarker concentrations generally decreased over the study period, except for mono-2-ethyl-5-carboxypentyl terephthalate. Overall, EDC biomarkers at 3 and/or 6 months of age were not associated with an increased risk of ASD or Non-TD, and a few showed significant inverse associations. However, when assessing longitudinal changes in MSEL scores over the four assessment time points, elevated monoethyl
phthalate (MEP) was significantly associated with reduced scores in the composite score (β = -0.16, 95% CI: 0.31, -0.02) and subscales of fine motor skills (β = -0.09, 95%CI: 0.17, 0.00), and visual reception (β = -0.11, 95% CI: 0.23, 0.01). Additionally, the sum of metabolites of di (2-ethylhexyl) terephthalate (ƩDEHTP) was associated with poorer visual reception (β = -0.09, 95% CI: 0.16, -0.02), and decreased composite scores (β = -0.11, 95% CI: 0.21, -0.01). Mixtures analyses using quantile g-computation analysis did not show a significant association between mixtures of EDC biomarkers and MSEL subscales or composite scores.
CONCLUSIONS: These findings highlight the potential importance of infant exposures on cognitive development. Future research can help further investigate whether early infant exposures are associated with longer-term deficits and place special attention on EDCs with increasing temporal trends and whether they may adversely affect neurodevelopment.