{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:36:52Z","timestamp":1790897812208,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]},{"name":"National Institutes of Health","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"National Institutes of Health","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"National Institutes of Health","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"National Institutes of Health","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]},{"name":"Stanford March of Dimes Prematurity Research Center","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"Stanford March of Dimes Prematurity Research Center","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"Stanford March of Dimes Prematurity Research Center","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"Stanford March of Dimes Prematurity Research Center","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]},{"name":"Stanford Dunlevie MFM Center for Discovery, Innovation and Clinical Impact","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"Stanford Dunlevie MFM Center for Discovery, Innovation and Clinical Impact","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"Stanford Dunlevie MFM Center for Discovery, Innovation and Clinical Impact","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"Stanford Dunlevie MFM Center for Discovery, Innovation and Clinical Impact","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]},{"name":"H&amp;H Evergreen Fund","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"H&amp;H Evergreen Fund","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"H&amp;H Evergreen Fund","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"H&amp;H Evergreen Fund","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]},{"name":"Novo Nordisk Foundation","award":["HL139844"],"award-info":[{"award-number":["HL139844"]}]},{"name":"Novo Nordisk Foundation","award":["UL1 TR001085"],"award-info":[{"award-number":["UL1 TR001085"]}]},{"name":"Novo Nordisk Foundation","award":["UL1 TR003142"],"award-info":[{"award-number":["UL1 TR003142"]}]},{"name":"Novo Nordisk Foundation","award":["NNF19OC0054286"],"award-info":[{"award-number":["NNF19OC0054286"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertensive disorders of pregnancy are associated with a higher risk of later cardiovascular disease, but the mechanistic links are unknown. We recruited two groups of women, one during pregnancy and another at least two years after delivery, including both cases (with a hypertensive disorder of pregnancy) and controls (with a normotensive pregnancy). We measured metabolites using liquid chromatography\u2013mass spectroscopy and applied machine learning to identify metabolomic signatures at three time points: antepartum, postpartum, and mid-life. The mean ages of the pregnancy cohort (58 cases, 46 controls) and the mid-life group (71 cases, 74 controls) were 33.8 and 40.8 years, respectively. The levels of 157 metabolites differed significantly between the cases and the controls antepartum, including 19 acylcarnitines, 12 gonadal steroids, 11 glycerophospholipids, nine fatty acids, six vitamin D metabolites, and four corticosteroids. The machine learning model developed using all antepartum metabolite levels discriminated well between the cases and the controls antepartum (c-index = 0.96), postpartum (c-index = 0.63), and in mid-life (c-index = 0.60). Levels of 10,20-dihydroxyeicosanoic acid best distinguished the cases from the controls both antepartum and postpartum. These data suggest that the pattern of differences in metabolites found antepartum continues to distinguish women who had a hypertensive disorder of pregnancy from women with a normotensive pregnancy for years after delivery.<\/jats:p>","DOI":"10.3390\/ijms26136150","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T06:55:13Z","timestamp":1750920913000},"page":"6150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4686-9441","authenticated-orcid":false,"given":"Mark A.","family":"Hlatky","sequence":"first","affiliation":[{"name":"Department of Health Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hung","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Bararpour","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina M.","family":"Sorondo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-2806","authenticated-orcid":false,"given":"Nicholas J.","family":"Leeper","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7640-2693","authenticated-orcid":false,"given":"Frank","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia L.","family":"Stefanick","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6849-9985","authenticated-orcid":false,"given":"Heather A.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6785","authenticated-orcid":false,"given":"Mads","family":"Melbye","sequence":"additional","affiliation":[{"name":"Danish Cancer Institute, and Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oshra","family":"Sedan","sequence":"additional","affiliation":[{"name":"Department of Health Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1205-6936","authenticated-orcid":false,"given":"Ronald J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0784-7987","authenticated-orcid":false,"given":"Michael P.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, 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