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Abstract：
Preeclampsia and preterm delivery (PTD) are believed to affect women\'s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population.
This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.
A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.
In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women\'s future cardiometabolic health.
This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.
A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.
In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women\'s future cardiometabolic health.
摘要：
子痫前期和早产（PTD）被认为影响妇女的长期健康，包括心血管疾病（CVD），但是生物基础在很大程度上是未知的。我们的目的是测试产妇产后代谢组学概况，尤其是与CVD相关的代谢物，根据有和没有先兆子痫的PTD亚型而变化，在美国城市，低收入多民族人口。
这项研究,波士顿出生队列,包括980名接受足月分娩的妇女，79患有医学上指示的PTD（mPTD）和先兆子痫，52只带mPTD，和219患有自发性PTD(sPTD)。通过液相色谱-质谱法进行产后血浆中的代谢组学分析。线性回归模型用于评估每种代谢物与mPTD和先兆子痫的关联。仅限mPTD,和sPTD，分别,调整相关协变量。应用加权基因共表达网络分析来研究与PTD/先兆子痫亚组相关的相互关联的代谢物。应用Bonferroni校正来解释多次测试。
分析了总共380种已知代谢物。与术语对照相比，患有mPTD和先兆子痫的女性显示36种代谢物的显着增加，主要代表酰基肉碱和多种类型的脂质(二酰基甘油，三酰基甘油,磷酸胆碱，和溶血磷酰胆碱），以及包括核苷酸在内的11种代谢物的减少，类固醇,和胆固醇酯(CEs)(P<1.3×10-4)。二酰基甘油的变化，三酰基甘油,与仅患有mPTD的女性相比，患有mPTD和先兆子痫的女性的CEs仍然显着。相比之下,仅患有mPTD的女性和足月对照组之间的代谢物差异仅在磷脂酰乙醇胺类别中可见。女性sPTD患者16种代谢产物水平差异显著,主要为氨基酸,核苷酸，和类固醇类与术语对照相比，其中，邻氨基苯甲酸,胆红素,和类固醇在mPTD和先兆子痫的女性中也有共同的关联.
在这个美国高危女性样本中，PTD/先兆子痫亚组均显示与产妇产后血浆代谢产物的一些独特和共有的关联。包括那些已知是未来CVD的预测因子。这些发现,如果已验证，可能为临床观察到的PTD/先兆子痫亚组的代谢组学改变及其对女性未来心脏代谢健康的影响提供新的见解。
这项研究,波士顿出生队列,包括980名接受足月分娩的妇女，79患有医学上指示的PTD（mPTD）和先兆子痫，52只带mPTD，和219患有自发性PTD(sPTD)。通过液相色谱-质谱法进行产后血浆中的代谢组学分析。线性回归模型用于评估每种代谢物与mPTD和先兆子痫的关联。仅限mPTD,和sPTD，分别,调整相关协变量。应用加权基因共表达网络分析来研究与PTD/先兆子痫亚组相关的相互关联的代谢物。应用Bonferroni校正来解释多次测试。
分析了总共380种已知代谢物。与术语对照相比，患有mPTD和先兆子痫的女性显示36种代谢物的显着增加，主要代表酰基肉碱和多种类型的脂质(二酰基甘油，三酰基甘油,磷酸胆碱，和溶血磷酰胆碱），以及包括核苷酸在内的11种代谢物的减少，类固醇,和胆固醇酯(CEs)(P<1.3×10-4)。二酰基甘油的变化，三酰基甘油,与仅患有mPTD的女性相比，患有mPTD和先兆子痫的女性的CEs仍然显着。相比之下,仅患有mPTD的女性和足月对照组之间的代谢物差异仅在磷脂酰乙醇胺类别中可见。女性sPTD患者16种代谢产物水平差异显著,主要为氨基酸,核苷酸，和类固醇类与术语对照相比，其中，邻氨基苯甲酸,胆红素,和类固醇在mPTD和先兆子痫的女性中也有共同的关联.
在这个美国高危女性样本中，PTD/先兆子痫亚组均显示与产妇产后血浆代谢产物的一些独特和共有的关联。包括那些已知是未来CVD的预测因子。这些发现,如果已验证，可能为临床观察到的PTD/先兆子痫亚组的代谢组学改变及其对女性未来心脏代谢健康的影响提供新的见解。
