孕期邻苯二甲酸酯暴露与学龄前儿童行为问题的关联与白质微观结构有关。
White matter microstructure mediates the association between prenatal exposure to phthalates and behavior problems in preschool children.
机构信息
Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada; Department of Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, Canada.
出版信息
Environ Res. 2020 Mar;182:109093. doi: 10.1016/j.envres.2019.109093. Epub 2019 Dec 26.
BACKGROUND
Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored.
OBJECTIVE
This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children.
METHODS
Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated.
RESULTS
Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI = 0.01, 0.23) through MD of the right pyramidal fibers.
DISCUSSION
This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.
背景
先前的研究报告表明，产前暴露于邻苯二甲酸酯与儿童行为问题之间存在关联；然而，这些关联背后的神经机制还相对未知。
目的
本研究旨在探讨微观结构白质是否可能作为产前邻苯二甲酸酯暴露与学龄前儿童行为问题之间关联的中介。
方法
本研究的数据来自前瞻性妊娠队列的子样本，即阿尔伯塔省妊娠结局与营养研究（APrON）。如果母亲在妊娠中期提供了尿液样本、如果孩子在 3-5 岁时成功完成了磁共振成像（MRI）扫描、并且在 MRI 扫描后 6 个月内完成了儿童行为检查表，则纳入母子对。从尿液样本中计算出高（HMWP）和低分子量邻苯二甲酸酯（LMWP）的摩尔总和。研究了产前邻苯二甲酸酯浓度与 10 条主要白质束的分数各向异性（FA）和平均扩散系数（MD）以及学龄前行为问题之间的关系。
结果
母体产前邻苯二甲酸酯浓度与右侧下额枕束（IFO）、右侧锥体束、左侧和右侧钩束（UF）的 MD 以及左侧下纵束（ILF）的 FA 相关。中介分析表明，HMWP 产前暴露通过右侧 IFO 的 MD 与内化问题（路径 ab=0.09，CI=0.02，0.20）和外化问题（路径 ab=0.09，CI=0.01，0.19）间接相关，通过右侧锥体束的 MD 与内化问题相关（路径 ab=0.11，CI=0.01，0.23）。
讨论
本研究首次提供了产前邻苯二甲酸酯暴露与儿童神经相关性的证据。结果表明，产前邻苯二甲酸酯暴露可能与 IFO、锥体束、UF 和 ILF 的微观结构白质有关。此外，右侧 IFO 和锥体束的 MD 可能传递儿童行为问题的风险。
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