Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva
Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva
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DOI：
10.1016/j.metabol.2017.07.001
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发表时间：
2017-11-01
影响因子：
9.8
通讯作者：
Oken, Emily
中科院分区：
文献类型：
--
作者：
Perng, Wei;Rifas-Shiman, Sheryl L.;Oken, Emily
语境。代谢组学已成为表征生物标志物和阐明不良健康结果背后的生理过程的强大工具。妊娠期和婴儿期是代谢疾病风险发展的关键时期，人们对这些关系知之甚少。 目标。确定与出生尺寸相关的脐带血代谢模式；并研究与出生体重相关的代谢模式以及支链氨基酸 (BCAA) 代谢模式与一系列新生儿和围产期特征的关系。方法。使用非靶向质谱法，我们对 126 对母子的脐带血中的代谢物进行了定量。排除 103 种外源物质后，我们使用主成分分析 (PCA) 将剩余的 606 种代谢物合并为主成分（“因子”）。接下来，我们确定了与胎龄和性别标准化出生体重 z 评分 (BW/GA) 相关的因素，并使用多元线性回归检查了 BW/GA 相关模式和 BCAA 模式与脐带血胰岛素、瘦素、脂联素、胰岛素样生长因子 (IGF)-1、IGF-2 和 IGF 结合蛋白 3 (IGFBP-3) 的关联。最后，我们检查了母体/围产期特征与脐带血代谢模式的关联。结果。平均 BW/GA z 分数为 0.27 +/- 0.98 单位。大约一半的婴儿是男性（52.4%）和白人（57.1%）。在 PCA 确定的 6 个因子中，其中一个与较高的 BW/GA 相关：因子 5，其包含参与能量产生（苹果酸、琥珀酸、富马酸）和核苷酸周转（5-单磷酸肌苷、5-单磷酸腺苷、5-单磷酸胞苷）途径的代谢物。在多变量分析中，即使在调整 IGFBP-3 后，因子 5 也与较高的脐带血瘦素 (1.64 [95% CI: 0.42, 2.871 ng/mL) 和 IGF-1 (3.35 [0.25, 6.44] ng/mL) 相关。 BCAA 模式与较高的 BW/GA（0.20 [0.03, 0.36] z 分数）和 IGFBP-3（106.5 [44.7, 168.2] ng/mL）相关。母体特征与这两种代谢模式均无关；然而，剖腹产出生的婴儿在因子 5 方面表现出较高的得分，并且妊娠长度与 BCAA 模式呈负相关。结论。脐带血能量产生和 DNA/RNA 周转途径中的代谢物与出生时较大的体型以及较高的瘦素和 IGF-1 相关。同样，BCAA 模式与较大的出生体重和 IGFBP-3 相关。 (C) 2017 Elsevier Inc. 保留所有权利。
Context. Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk.Objectives. To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics.Methods. Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components ("factors"). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns.Results. Mean BW/GA z-score was 0.27 +/- 0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.871 ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern.Conclusions. Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3. (C) 2017 Elsevier Inc. All rights reserved.