Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Dissecting the relationship between plasma and tissue metabolome in a cohort of women with obesity: Analysis of subcutaneous and visceral adipose, muscle, and liver

“…This has made the circulating metabolites important targets in clinical studies. To date, metabolomics has been successfully applied to identify circulating markers that have the potential to diagnose cardiometabolic diseases at an early stage or provide additional prognostic value 5–8 . Metabolomic profiling of blood samples has also provided a systemic snapshot of metabolic alterations under pathophysiological conditions, hence opening a window for mechanistic investigation of the underpinning pathways during disease development 9 .…”

Effects of ambient particulate exposure on blood lipid levels in hypertension inpatients

“…SPSS was used to describe the mean ± standard deviation (Mean ± SD) of blood lipid indexes in three groups of “hypertension with arteriosclerosis,” “hypertension without arteriosclerosis” and “total hypertension.” Age, gender and hospitalization date were used as covariates for covariance analysis to compare the differences in the mean concentrations of blood lipid indexes among the three groups. If differences were statistically significant, Bonferroni's method was used for multiple comparisons ( 21 ). The central and discrete trends of air pollution and meteorological data were described, and the differences in air pollution concentrations between adjacent years were compared using the Kruskal-Wallis test ( 22 ).…”

Identification of Biomarkers for Preeclampsia Based on Metabolomics

“…Renal dysfunction is seen in asymptomatic women in whom PE will eventually develop, and proteinuria and decreased renal function are classic hallmarks of PE. 50 The levels of related low molecular weight substances, such as creatinine, 15,22,32,38,39,44 lactate, 27,32,45 urea, 9,23,28 and creatine, 15,20,23,32,39 could be used to monitor renal function and to assist the diagnosis of PE.…”

“…metabolites that were related with PE. Meanwhile, lipids 8,18 and related metabolites, such as phosphatidylcholines, 13,15,23,25,26,28,32,48 lysophosphatidylcholine, 11,13,15,23,25,48 glycerophosphocholine, 9,20,25,35 acylcarnitines, 15 and sphingolipids 13 were generally detected. Thirty-three metabolites were reported in ≥ 3 studies (Table 2).…”