Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term hea
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RESEARCH ARTICLE
Open Access
Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health Xiumei Hong1*† , Boyang Zhang2†, Liming Liang3,4, Yan Zhang2, Yuelong Ji1, Guoying Wang1, Hongkai Ji2, Clary B. Clish5, Irina Burd6, Colleen Pearson7, Barry Zuckerman7, Frank B. Hu3,8,9 and Xiaobin Wang1,10
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. (Continued on next page)
* Correspondence: [email protected] † Xiumei Hong and Boyang Zhang contributed equally to this work. 1 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 Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproductio
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