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儿童时期接触环境化学物质与先天性心脏病的神经发育结局。

Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease.

机构信息

Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.

Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.

出版信息

PLoS One. 2022 Nov 17;17(11):e0277611. doi: 10.1371/journal.pone.0277611. eCollection 2022.

Abstract

BACKGROUND

Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown.

METHODS

This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores.

RESULTS

One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points [2.5th and 97.5th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes.

CONCLUSIONS

Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.

摘要

背景

患有先天性心脏缺陷的儿童有神经发育障碍的风险增加。日常生活中环境化学暴露对先天性心脏缺陷幼儿神经发育结局的影响尚不清楚。

方法

本前瞻性研究调查了儿童心脏手术后早期暴露于环境化学混合物对神经发育结局的影响。使用贝利婴幼儿发育量表第三版(Bayley Scales of Infant and Toddler Development-III)在 18 个月龄时评估结果。同时测量了暴露于农药、酚类、对羟基苯甲酸酯和邻苯二甲酸酯的生物标志物的尿浓度,以及血铅、汞和尼古丁水平。贝叶斯轮廓回归和加权分位数和回归用于评估生物标志物混合物与神经发育评分之间的关联。

结果

共纳入 140 名婴儿,110 名(79%)在 18 个月龄时返回。贝叶斯轮廓回归分析确定了 6 个生物标志物暴露簇;该模式由 30 种生物标志物中的 15 种驱动,尤其是 13 种邻苯二甲酸酯生物标志物。与最低暴露组相比,最高暴露组儿童的调整后语言评分显著降低了-9.41 分(95%CI:-17.2,-1.7),调整后运动评分显著降低了-4.9 分(-9.5,-0.4)。整体暴露-反应关系的加权分位数和回归模型显示,调整后的运动评分显著降低(β=-2.8 分[2.5 分位数和 97.5 分位数:-6.0,-0.6])。几种邻苯二甲酸酯、一种对羟基苯甲酸酯和一种酚类物质的加权分位数和回归指数权重表明它们与神经发育结局较差有关。

结论

与其他儿童一样,患有先天性心脏缺陷的婴儿在日常生活中会接触到复杂的环境化学混合物。该人群中生物标志物浓度较高与语言和运动技能表现明显较差相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c542/9671412/780dafb7cefc/pone.0277611.g001.jpg

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