Abstract：
Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods.
In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.
Metal\'s levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.
This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.
In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.
Metal\'s levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.
This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.
摘要：
背景：母体接触金属可能会对新生儿的健康构成风险，然而,潜在的机制仍然模棱两可。在这里，我们旨在通过代谢组学方法研究金属暴露对出生结局的影响,并揭示代谢物在暴露-结局相关性中的重要性.
方法：在我们的研究中，在2006年至2011年间从南京医科大学附属医院招募的292对母亲。我们测量了15种金属(汞，铅,钒，砷,锌，镉,铷,铜，钴,铁,钼,锶,铊,通过使用电感耦合等离子体质谱法和超高效液相色谱高分辨率准确质谱法，分别。多步统计分析策略，包括全暴露组关联研究(ExWAS)模型，通过变量选择模型和多重暴露模型,系统评价了个体和混合金属暴露与出生结局的相关性.此外，使用线性回归模型鉴定与金属暴露和出生结局相关的差异代谢物.
结果：母体血清中的金属含量范围为0.05μg/L至1864.76μg/L。在ExWAS模型中,母亲砷暴露与出生体重呈负相关(β=188.83;95%CI:-368.27,-9.39),而母体汞暴露与出生体重呈正相关(β=533.65;95CI:179.40,887.90)。此外，汞每单位增加(1ng/mL-log转化)与胎龄1.82周增加(95CI:0.85,2.79)相关.随后通过变量选择模型和多重暴露模型验证了这些发现。代谢组学分析进一步揭示了3-甲基腺嘌呤在砷暴露与出生体重之间的关系中的重要作用。
结论：这项研究提供了新的流行病学证据，表明金属暴露与新生儿出生结局之间存在关联。并强调代谢物生物标志物的潜在作用及其在监测不良分娩结局方面的重要性.
方法：在我们的研究中，在2006年至2011年间从南京医科大学附属医院招募的292对母亲。我们测量了15种金属(汞，铅,钒，砷,锌，镉,铷,铜，钴,铁,钼,锶,铊,通过使用电感耦合等离子体质谱法和超高效液相色谱高分辨率准确质谱法，分别。多步统计分析策略，包括全暴露组关联研究(ExWAS)模型，通过变量选择模型和多重暴露模型,系统评价了个体和混合金属暴露与出生结局的相关性.此外，使用线性回归模型鉴定与金属暴露和出生结局相关的差异代谢物.
结果：母体血清中的金属含量范围为0.05μg/L至1864.76μg/L。在ExWAS模型中,母亲砷暴露与出生体重呈负相关(β=188.83;95%CI:-368.27,-9.39),而母体汞暴露与出生体重呈正相关(β=533.65;95CI:179.40,887.90)。此外，汞每单位增加(1ng/mL-log转化)与胎龄1.82周增加(95CI:0.85,2.79)相关.随后通过变量选择模型和多重暴露模型验证了这些发现。代谢组学分析进一步揭示了3-甲基腺嘌呤在砷暴露与出生体重之间的关系中的重要作用。
结论：这项研究提供了新的流行病学证据，表明金属暴露与新生儿出生结局之间存在关联。并强调代谢物生物标志物的潜在作用及其在监测不良分娩结局方面的重要性.
