The Florey Institute for Neuroscience and Mental Health, Australia; Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, University of Melbourne, Victoria, Australia.
Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, University of Melbourne, Victoria, Australia.
Neurotoxicology. 2020 Sep;80:20-28. doi: 10.1016/j.neuro.2020.05.006. Epub 2020 May 30.
Prenatal phthalate chemicals may have adverse effects on brain development by various mechanisms including oxidant damage. However, birth cohort findings have been conflicting. This study aimed to (i) investigate the interplay between maternal prenatal phthalate levels, infant genetic vulnerability to oxidative stress, and child neurodevelopment and (ii) examine combined putative oxidant exposures. In a population-based birth cohort of 1064 women with prenatal recruitment in Victoria, Australia, maternal urine was collected at 36 weeks of pregnancy and phthalate metabolite concentrations measured. An unweighted genetic score for oxidative stress was made using a candidate gene approach. Cognition was assessed using the BAYLEY-III at two years (n = 678). Parents completed questionnaires for doctor diagnosed autism spectrum disorder (ASD) (1.4 %), ASD traits (4.9 %) and child inattention/hyperactivity (n = 791). Analyses included multiple linear and logistic regression. Higher prenatal phthalate levels and a higher oxidative stress genetic score were each associated with subsequent ASD. Several oxidative stress-related SNPs modified the association between prenatal phthalates and ASD and other outcomes. Consistent patterns were evident across gene score-phthalate combinations for cognition, ASD, ASD traits and inattention/hyperactivity. Other putative oxidant factors such as prenatal smoking further increased risk. Prenatal phthalate levels and infant oxidative stress-related genetic vulnerability are associated with adverse neurodevelopment. Combined exposures are important. Current recommendations and regulation on maternal phthalate exposure during pregnancy require re-evaluation.
产前邻苯二甲酸酯化学物质可能通过各种机制对大脑发育产生不良影响，包括氧化剂损伤。然而，出生队列的研究结果存在冲突。本研究旨在：（i）研究母体产前邻苯二甲酸酯水平、婴儿对氧化应激的遗传易感性与儿童神经发育之间的相互作用；（ii）检验潜在氧化剂暴露的综合作用。在澳大利亚维多利亚州的一个基于人群的 1064 名妇女的出生队列中，在妊娠 36 周时收集了母亲的尿液，并测量了邻苯二甲酸代谢物浓度。采用候选基因方法构建了一个未加权的氧化应激遗传评分。在两岁时使用 BAYLEY-III 评估认知（n=678）。父母完成了自闭症谱系障碍（ASD）（1.4%）、ASD 特征（4.9%）和儿童注意力不集中/多动（n=791）的问卷调查。分析包括多元线性和逻辑回归。较高的产前邻苯二甲酸酯水平和较高的氧化应激遗传评分均与随后的 ASD 相关。几个与氧化应激相关的 SNP 修饰了产前邻苯二甲酸酯与 ASD 及其他结果之间的关联。在认知、ASD、ASD 特征和注意力不集中/多动等方面，基因评分-邻苯二甲酸酯组合之间存在一致的模式。其他潜在的氧化剂因素，如产前吸烟，进一步增加了风险。产前邻苯二甲酸酯水平和婴儿氧化应激相关的遗传易感性与不良神经发育有关。综合暴露很重要。目前关于妊娠期间母体邻苯二甲酸酯暴露的建议和监管需要重新评估。
