Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
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DOI：
10.1186/s13229-020-0315-z
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发表时间：
2020-01-16
期刊：
影响因子：
6.2
通讯作者：
Silfverdal, Sven-Arne
中科院分区：
文献类型：
--
作者：
Egorova, Olga;Myte, Robin;Silfverdal, Sven-Arne
自闭症谱系障碍（ASD）是在产前发育过程中遗传和环境因素相互作用的结果。由于在妊娠早期确定与后代ASD风险相关的母体生物标志物可能会带来新的干预策略，我们使用单变量逻辑回归和多变量网络分析研究了与后代ASD发生相关的母体代谢生物标志物。方法收集100例诊断为ASD的后代的妇女和100例正常发育后代的对照妇女在妊娠14周时的血清样本。测定了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）和与叶酸（维生素B-9）代谢、生活方式因素相关的生物标志物，以及c反应蛋白（CRP）、犬尿氨酸-色氨酸比率（KTR）和作为炎症和免疫激活标志物的新蝶呤。结果我们发现弱证据表明母体血清叶酸浓度升高与ASD发生率增加呈正相关（OR / 1 SD增加：1.70,95% CI 1.22-2.37， FDR调整后P = 0.07）。多元网络分析证实了生物标志物之间预期的内在生化关系。炎症标志物和维生素D-3水平均未显示出与后代发生ASD的关联，而这些都被假设与ASD病因有关。结论妊娠早期母亲血清叶酸水平高可能与后代ASD的发生有关。由于血液叶酸水平可能与营养摄入、细胞叶酸状态和其他b族维生素的状态有复杂的关系，因此目前还无法对这一观察结果背后的生理机制做出推断。因此，有必要在更大的材料中进行进一步的研究，以阐明母亲血液中叶酸水平在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。
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 B-9) 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 D-3 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.