Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205-2179, USA.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA.
BMC Med. 2020 Oct 13;18(1):277. doi: 10.1186/s12916-020-01741-4.
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). 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.
子痫前期和早产（PTD）被认为会影响女性的长期健康，包括心血管疾病（CVD），但其中的生物学基础在很大程度上尚不清楚。我们旨在检测在美国城市中，以多民族的低收入人群为研究对象，母体产后代谢组学特征，尤其是与 CVD 相关的代谢物，是否会根据伴有或不伴有子痫前期的 PTD 亚型而有所不同。
本研究来自波士顿出生队列，共纳入 980 名足月分娩妇女、79 名因医学原因导致的早产（mPTD）合并子痫前期、52 名单纯 mPTD 和 219 名自发性早产（sPTD）妇女。采用液相色谱-质谱法对产后血浆进行代谢组学分析。使用线性回归模型分别评估每个代谢物与 mPTD 合并子痫前期、单纯 mPTD 和 sPTD 的相关性，调整相关协变量。应用加权基因共表达网络分析（WGCNA）来研究与 PTD/子痫前期亚组相关的相互关联的代谢物。采用 Bonferroni 校正来校正多重检测。
共分析了 380 种已知代谢物。与足月对照组相比，mPTD 合并子痫前期妇女的 36 种代谢物水平显著升高，主要为酰基肉碱和多种脂质（二酰甘油、三酰甘油、磷酸胆碱和溶血磷酯），11 种代谢物水平显著降低，包括核苷酸、甾体和胆固醇酯（CE）（P 值均<1.3×10）。与单纯 mPTD 妇女相比，mPTD 合并子痫前期妇女的二酰甘油、三酰甘油和 CE 变化仍然显著。相比之下，mPTD 妇女与足月对照组之间的代谢物差异仅见于磷脂酰乙醇胺类。与足月对照组相比，sPTD 妇女的 16 种代谢物水平差异显著，主要在氨基酸、核苷酸和甾体类，其中，邻氨基苯甲酸、胆红素和甾体也与 mPTD 合并子痫前期妇女存在共同关联。
在本研究中，美国高危妇女的 PTD/子痫前期亚组均与母体产后血浆代谢物有一些独特和共同的关联，其中包括已知的 CVD 预测因子。如果这些发现得到验证，可能为临床上观察到的 PTD/子痫前期亚组的代谢物改变提供新的见解，并为女性未来的心脏代谢健康提供启示。
