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

BMC Medicine

Clary B. Clish¹  Guoying Wang²  Xiumei Hong²  Yuelong Ji²  Xiaobin Wang³  Hongkai Ji⁴  Yan Zhang⁴  Boyang Zhang⁴  Liming Liang⁵  Frank B. Hu⁶  Colleen Pearson⁷  Barry Zuckerman⁷  Irina Burd⁸ 

[1] Broad Institute of MIT and Harvard University, Cambridge, MA, USA;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, 21205-2179, Baltimore, MD, USA;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, 21205-2179, Baltimore, MD, USA;Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St, 21205, Baltimore, MD, USA;Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 02118, Boston, MA, USA;Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 21287, Baltimore, MD, USA;

关键词: Preterm delivery;    Preeclampsia;    Medically indicated preterm delivery;    Spontaneous preterm delivery;    Postpartum;    Metabolome;   

DOI  :  10.1186/s12916-020-01741-4

来源: Springer

【 摘 要 】

BackgroundPreeclampsia 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.MethodsThis 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.ResultsA 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.ConclusionIn 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.

【 授权许可】

CC BY