BACKGROUND Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. METHODS Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. RESULTS We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. CONCLUSIONS Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

中文翻译：

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孕早期孕妇血中叶酸的状况以及后代自闭症谱系障碍的发生：62种血清生物标志物的研究。

背景技术自闭症谱系障碍（ASD）由产前发育过程中遗传因素与环境因素之间的相互作用演变而来。由于在妊娠早期确定与后代ASD风险相关的母亲生物标志物可能会导致新的干预策略，因此我们使用单变量逻辑回归和多元网络分析调查了与后代ASD发生有关的母亲代谢生物标志物。方法在怀孕的第14周收集100例被诊断患有ASD的后代妇女和100例典型发育的后代对照妇女的血清样本。确定了62种代谢生物标志物的浓度，包括氨基酸，维生素（A，B，D，E和K）以及与叶酸代谢相关的生物标志物（维生素B9），生活方式因素，以及C反应蛋白（CRP），犬尿氨酸-色氨酸比（KTR）和新蝶呤作为炎症和免疫激活的标志物。结果我们发现，母体血清叶酸含量较高与ASD发生率增加之间呈正相关的证据不充分（OR每增加1 SD：1.70，95％CI 1.22-2.37，FDR调整P = 0.07）。多元网络分析证实了生物标记之间预期的内部生化关系。均被认为与ASD病因有关的炎症标志物和维生素D3水平均未显示与后代中ASD的发生有关。结论我们的研究结果表明，孕早期孕妇血清叶酸水平高可能与后代ASD的发生有关。由于血液中的叶酸水平可能与营养摄入，细胞叶酸状况以及其他B-维生素的状况之间存在复杂的关系，因此目前尚无法推断出这一现象背后的生理机制。因此，有必要进行进一步的研究，以便阐明大剂量材料中母亲叶酸状态在ASD风险中的潜在作用和机制以及与其他潜在风险因素的相互作用。