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Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography\u2014mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values &lt; 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value &lt; 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine\/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.<\/jats:p>","DOI":"10.3390\/metabo12121169","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T03:24:09Z","timestamp":1669260249000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development"],"prefix":"10.3390","volume":"12","author":[{"given":"Sophia M.","family":"Blaauwendraad","sequence":"first","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama J.","family":"Wahab","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-3825","authenticated-orcid":false,"given":"Bas B.","family":"van Rijn","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-7165","authenticated-orcid":false,"given":"Berthold","family":"Koletzko","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children\u2019s Hospital, LMU\u2014Ludwig-Maximilians Universit\u00e4t M\u00fcnchen, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-0041","authenticated-orcid":false,"given":"Vincent W. V.","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Gaillard","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0140-6736(06)68397-9","article-title":"WHO analysis of causes of maternal death: A systematic review","volume":"367","author":"Khan","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/aje\/kwr151","article-title":"Blood Pressure in Different Gestational Trimesters, Fetal Growth, and the Risk of Adverse Birth Outcomes: The Generation R Study","volume":"174","author":"Bakker","year":"2011","journal-title":"Am. 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