Inorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes. Data from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012) with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10). Among urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise. Tissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.

中文翻译：

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一碳代谢因子的母体血清浓度改变了砷甲基化效率和出生体重生物标志物之间的关联

无机砷 (iAs) 是一种普遍存在的准金属和饮用水污染物。在多项研究中，产前暴露与出生结果相关。在新陈代谢过程中，iAs 依次甲基化为单甲基化和二甲基化砷物质（MMA 和 DMA）以促进全身清除。低效甲基化（例如，较高的尿 MMA 百分比）与某些 iAs 相关疾病的风险增加有关。一碳代谢因子影响 iAs 甲基化，改变成人的毒性，值得在产前进一步研究。本研究的目的是评估叶酸、维生素 B12 和同型半胱氨酸作为 iAs 甲基化效率生物标志物与出生结果之间关系的调节剂。使用了来自砷暴露生物标志物 (BEAR) 妊娠队列 (2011–2012) 的数据，其中包括母体尿液和脐带血清砷生物标志物以及母体血清叶酸、维生素 B12 和同型半胱氨酸浓度。使用临床截断值和中值拆分对一碳代谢因子进行二分法。多变量线性回归模型适用于评估每种生物标志物与总体出生结果以及单碳代谢因子水平之间的关联。完整模型和简化模型的似然比检验用于检验统计相互作用在加性尺度 (α = 0.10) 上的显着性。在尿液生物标志物中，U-MMA 百分比与出生体重的相关性最强（β = − 23.09, 95% CI: − 44.54, − 1.64）。更大，在缺乏 B12 (β = − 28.69, 95% CI: − 53.97, − 3.42) 或患有高同型半胱氨酸血症 (β = − 63.29, 95% CI: − 154.77, 28.19). 一般来说，叶酸和维生素 B12 血清浓度较高（或同型半胱氨酸血清浓度较低）的母亲所生婴儿的平均出生体重差异会减小。维生素 B12 和同型半胱氨酸的影响修饰在某些关联的加法量表上是显着的。胎龄的结果不太引人注目，与 C-tAs 相关的大约一周平均差异 (β = 0.87, 95% CI: 0, 1.74)，但在其他方面没有意义。iAs 及其代谢物（例如，% MMAs）的组织分布可能因血清叶酸浓度而异，怀孕期间维生素 B12 和同型半胱氨酸。这代表了一种潜在的机制，通过这种机制，母亲的饮食可以改变产前暴露于 iAs 的危害。