{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:42:52Z","timestamp":1787884972713,"version":"build-2784847793"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"General Projects of Changzhou Medical Center","award":["CMCB202216"],"award-info":[{"award-number":["CMCB202216"]}]},{"name":"General Project of Jiangsu Provincial Health Commission","award":["M2021079"],"award-info":[{"award-number":["M2021079"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Observational studies have revealed that metabolic disorders are closely related to the development of preeclampsia (PE). However, there is still a research gap on the causal role of metabolites in promoting or preventing PE. We aimed to systematically explore the causal association between circulating metabolites and PE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) of 486 blood metabolites (7,824 participants) were extracted as instrumental variables (<jats:italic>P<\/jats:italic>\u2009&lt;\u20091\u2009\u00d7\u200910<jats:sup>\u2212\u20095<\/jats:sup>), GWAS summary statistics for PE were obtained from FinnGen consortium (7,212 cases and 194,266 controls) as outcome, and a two-sample Mendelian randomization (MR) analysis was conducted. Inverse variance weighted (IVW) was set as the primary method, with MR\u2013Egger and weighted median as auxiliary methods; the instrumental variable strength and confounding factors were also assessed. Sensitivity analyses including MR-Egger, Cochran\u2019s Q test, MR-PRESSO and leave-one-out analysis were performed to test the robustness of the MR results. For significant associations, repeated MR and meta-analysis were performed by another metabolite GWAS (8,299 participants). Furthermore, significantly associated metabolites were subjected to a metabolic pathway analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The instrumental variables for the metabolites ranged from 3 to 493. Primary analysis revealed a total of 12 known (e.g., phenol sulfate, citrulline, lactate and gamma-glutamylglutamine) and 11 unknown metabolites were associated with PE. Heterogeneity and pleiotropy tests verified the robustness of the MR results. Validation with another metabolite GWAS dataset revealed consistency trends in 6 of the known metabolites with preliminary analysis, particularly the finding that genetic susceptibility to low levels of arachidonate (20:4n6) and citrulline were risk factors for PE. The pathway analysis revealed glycolysis\/gluconeogenesis and arginine biosynthesis involved in the pathogenesis of PE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study identifies a causal relationship between some circulating metabolites and PE. Our study presented new perspectives on the pathogenesis of PE by integrating metabolomics with genomics, which opens up avenues for more accurate understanding and management of the disease, providing new potential candidate metabolic molecular markers for the prevention, diagnosis and treatment of PE. Considering the limitations of MR studies, further research is needed to confirm the causality and underlying mechanisms of these findings.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12905-024-03000-7","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T11:02:03Z","timestamp":1712314923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating genetic links between blood metabolites and preeclampsia"],"prefix":"10.1186","volume":"24","author":[{"given":"Qiannan","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"issue":"5","key":"3000_CR1","doi-asserted-by":"publisher","first-page":"e218401","DOI":"10.1001\/jamanetworkopen.2021.8401","volume":"4","author":"Y Yang","year":"2021","unstructured":"Yang Y, Le Ray I, Zhu J, Zhang J, Hua J, Reilly M, Preeclampsia, Prevalence. Risk factors, and pregnancy outcomes in Sweden and China. JAMA Netw Open. 2021;4(5):e218401. https:\/\/doi.org\/10.1001\/jamanetworkopen.2021.8401.","journal-title":"JAMA Netw Open"},{"issue":"5","key":"3000_CR2","doi-asserted-by":"publisher","first-page":"101123","DOI":"10.1016\/j.siny.2020.101123","volume":"25","author":"M Ma\u2019ayeh","year":"2020","unstructured":"Ma\u2019ayeh M, Costantine MM. Prevention of preeclampsia. Semin Fetal Neonatal Med. 2020;25(5):101123. https:\/\/doi.org\/10.1016\/j.siny.2020.101123.","journal-title":"Semin Fetal Neonatal Med"},{"issue":"2s","key":"3000_CR3","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.ajog.2021.11.1356","volume":"226","author":"E Jung","year":"2022","unstructured":"Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, Gotsch F, Erez O. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226(2s):844\u2013s866. https:\/\/doi.org\/10.1016\/j.ajog.2021.11.1356.","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"3000_CR4","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1097\/01.aog.0000437382.03963.88","volume":"122","author":"Hypertension in pregnancy","year":"2013","unstructured":"Hypertension in pregnancy. Report of the American College of Obstetricians and gynecologists\u2019 Task Force on hypertension in pregnancy. Obstet Gynecol. 2013;122(5):1122\u201331. https:\/\/doi.org\/10.1097\/01.aog.0000437382.03963.88.","journal-title":"Obstet Gynecol"},{"issue":"7","key":"3000_CR5","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1161\/circresaha.118.313276","volume":"124","author":"S Rana","year":"2019","unstructured":"Rana S, Lemoine E, Granger JP, Karumanchi SA, Preeclampsia. Pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094\u2013112. https:\/\/doi.org\/10.1161\/circresaha.118.313276.","journal-title":"Circ Res"},{"key":"3000_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02180-2","author":"A van der Spek","year":"2023","unstructured":"van der Spek A, Stewart ID, K\u00fchnel B, Pietzner M, Alshehri T, Gau\u00df F, Hysi PG, MahmoudianDehkordi S, Heinken A, Luik AI, et al. Circulating metabolites modulated by diet are associated with depression. Mol Psychiatry. 2023. https:\/\/doi.org\/10.1038\/s41380-023-02180-2.","journal-title":"Mol Psychiatry"},{"key":"3000_CR7","doi-asserted-by":"publisher","first-page":"645118","DOI":"10.3389\/fmed.2021.645118","volume":"8","author":"G Monni","year":"2021","unstructured":"Monni G, Atzori L, Corda V, Dessolis F, Iuculano A, Hurt KJ, Murgia F. Metabolomics in prenatal medicine: a review. Front Med (Lausanne). 2021;8:645118. https:\/\/doi.org\/10.3389\/fmed.2021.645118.","journal-title":"Front Med (Lausanne)"},{"issue":"5","key":"3000_CR8","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1080\/19396368.2018.1482968","volume":"64","author":"MGBF Nobakht","year":"2018","unstructured":"Nobakht MGBF. Application of metabolomics to preeclampsia diagnosis. Syst Biol Reprod Med. 2018;64(5):324\u201339. https:\/\/doi.org\/10.1080\/19396368.2018.1482968.","journal-title":"Syst Biol Reprod Med"},{"key":"3000_CR9","doi-asserted-by":"publisher","first-page":"e894","DOI":"10.6061\/clinics\/2019\/e894","volume":"74","author":"RT Souza","year":"2019","unstructured":"Souza RT, Mayrink J, Leite DF, Costa ML, Calderon IM, Rocha Filho EA, Vettorazzi J, Feitosa FE, Cecatti JG. Metabolomics applied to maternal and perinatal health: a review of new frontiers with a translation potential. Clin (Sao Paulo). 2019;74:e894. https:\/\/doi.org\/10.6061\/clinics\/2019\/e894.","journal-title":"Clin (Sao Paulo)"},{"key":"3000_CR10","doi-asserted-by":"publisher","first-page":"337","DOI":"10.2147\/clep.s353019","volume":"14","author":"M Yao","year":"2022","unstructured":"Yao M, Xiao Y, Yang Z, Ge W, Liang F, Teng H, Gu Y, Yin J. Identification of biomarkers for Preeclampsia based on Metabolomics. Clin Epidemiol. 2022;14:337\u201360. https:\/\/doi.org\/10.2147\/clep.s353019.","journal-title":"Clin Epidemiol"},{"issue":"5","key":"3000_CR11","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1007\/s00125-023-05879-7","volume":"66","author":"S Yuan","year":"2023","unstructured":"Yuan S, Merino J, Larsson SC. Causal factors underlying diabetes risk informed by mendelian randomisation analysis: evidence, opportunities and challenges. Diabetologia. 2023;66(5):800\u201312. https:\/\/doi.org\/10.1007\/s00125-023-05879-7.","journal-title":"Diabetologia"},{"issue":"1","key":"3000_CR12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","volume":"33","author":"GD Smith","year":"2004","unstructured":"Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33(1):30\u201342. https:\/\/doi.org\/10.1093\/ije\/dyh132.","journal-title":"Int J Epidemiol"},{"issue":"1","key":"3000_CR13","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1186\/s12967-022-03822-9","volume":"20","author":"J Li","year":"2022","unstructured":"Li J, Li C, Huang Y, Guan P, Huang D, Yu H, Yang X, Liu L. Mendelian randomization analyses in ocular disease: a powerful approach to causal inference with human genetic data. J Transl Med. 2022;20(1):621. https:\/\/doi.org\/10.1186\/s12967-022-03822-9.","journal-title":"J Transl Med"},{"issue":"6","key":"3000_CR14","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/ng.2982","volume":"46","author":"SY Shin","year":"2014","unstructured":"Shin SY, Fauman EB, Petersen AK, Krumsiek J, Santos R, Huang J, Arnold M, Erte I, Forgetta V, Yang TP, et al. An atlas of genetic influences on human blood metabolites. Nat Genet. 2014;46(6):543\u201350. https:\/\/doi.org\/10.1038\/ng.2982.","journal-title":"Nat Genet"},{"key":"3000_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/postmj\/qgad052","author":"L Ji","year":"2023","unstructured":"Ji L, Wang Y, Lu T, Yang J, Luo C, Qiu B. Identification of blood metabolites linked to the risk of intervertebral disc diseases: a comprehensive mendelian randomization study. Postgrad Med J. 2023. https:\/\/doi.org\/10.1093\/postmj\/qgad052.","journal-title":"Postgrad Med J"},{"issue":"13","key":"3000_CR16","doi-asserted-by":"publisher","first-page":"e028540","DOI":"10.1161\/jaha.122.028540","volume":"12","author":"G Qiu","year":"2023","unstructured":"Qiu G, Lin Y, Ouyang Y, You M, Zhao X, Wang H, Niu R, Li W, Xu X, Yan Q, et al. Nontargeted Metabolomics Revealed Novel Association between Serum Metabolites and Incident Acute Coronary Syndrome: a mendelian randomization study. J Am Heart Assoc. 2023;12(13):e028540. https:\/\/doi.org\/10.1161\/jaha.122.028540.","journal-title":"J Am Heart Assoc"},{"key":"3000_CR17","doi-asserted-by":"publisher","unstructured":"Yao Z, Jiang F, Luo H, Zhou J, Shi W, Xu S, Zhang Y, Dai F, Li X, Liu Z, et al. Causal effects of blood lipid traits on inflammatory Bowel diseases: a mendelian randomization study. Metabolites. 2023;13(6). https:\/\/doi.org\/10.3390\/metabo13060730.","DOI":"10.3390\/metabo13060730"},{"issue":"1","key":"3000_CR18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41588-022-01270-1","volume":"55","author":"Y Chen","year":"2023","unstructured":"Chen Y, Lu T, Pettersson-Kymmer U, Stewart ID, Butler-Laporte G, Nakanishi T, Cerani A, Liang KYH, Yoshiji S, Willett JDS, et al. Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases. Nat Genet. 2023;55(1):44\u201353. https:\/\/doi.org\/10.1038\/s41588-022-01270-1.","journal-title":"Nat Genet"},{"issue":"12","key":"3000_CR19","doi-asserted-by":"publisher","first-page":"13784","DOI":"10.1002\/cam4.6022","volume":"12","author":"Z Yun","year":"2023","unstructured":"Yun Z, Guo Z, Li X, Shen Y, Nan M, Dong Q, Hou L. Genetically predicted 486 blood metabolites in relation to risk of colorectal cancer: a mendelian randomization study. Cancer Med. 2023;12(12):13784\u201399. https:\/\/doi.org\/10.1002\/cam4.6022.","journal-title":"Cancer Med"},{"issue":"4","key":"3000_CR20","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1001\/jamapsychiatry.2018.4175","volume":"76","author":"KW Choi","year":"2019","unstructured":"Choi KW, Chen CY, Stein MB, Klimentidis YC, Wang MJ, Koenen KC, Smoller JW. Assessment of Bidirectional relationships between physical activity and depression among adults: a 2-Sample mendelian randomization study. JAMA Psychiatry. 2019;76(4):399\u2013408. https:\/\/doi.org\/10.1001\/jamapsychiatry.2018.4175.","journal-title":"JAMA Psychiatry"},{"issue":"11","key":"3000_CR21","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/asn.2016010098","volume":"27","author":"P Sekula","year":"2016","unstructured":"Sekula P, Del Greco MF, Pattaro C, K\u00f6ttgen A. Mendelian randomization as an Approach to assess causality using Observational Data. J Am Soc Nephrol. 2016;27(11):3253\u201365. https:\/\/doi.org\/10.1681\/asn.2016010098.","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"3000_CR22","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1161\/hypertensionaha.121.18617","volume":"79","author":"M Ardissino","year":"2022","unstructured":"Ardissino M, Slob EAW, Millar O, Reddy RK, Lazzari L, Patel KHK, Ryan D, Johnson MR, Gill D, Ng FS. Maternal hypertension increases risk of Preeclampsia and low fetal birthweight: genetic evidence from a mendelian randomization study. Hypertension. 2022;79(3):588\u201398. https:\/\/doi.org\/10.1161\/hypertensionaha.121.18617.","journal-title":"Hypertension"},{"issue":"7","key":"3000_CR23","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","volume":"37","author":"S Burgess","year":"2013","unstructured":"Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658\u201365. https:\/\/doi.org\/10.1002\/gepi.21758.","journal-title":"Genet Epidemiol"},{"key":"3000_CR24","doi-asserted-by":"publisher","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.2","volume":"4","author":"S Burgess","year":"2019","unstructured":"Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, Hartwig FP, Holmes MV, Minelli C, Relton CL, et al. Guidelines for performing mendelian randomization investigations. Wellcome Open Res. 2019;4:186. https:\/\/doi.org\/10.12688\/wellcomeopenres.15555.2.","journal-title":"Wellcome Open Res"},{"issue":"4","key":"3000_CR25","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s40471-017-0128-6","volume":"4","author":"J Zheng","year":"2017","unstructured":"Zheng J, Baird D, Borges MC, Bowden J, Hemani G, Haycock P, Evans DM, Smith GD. Recent developments in mendelian randomization studies. Curr Epidemiol Rep. 2017;4(4):330\u201345. https:\/\/doi.org\/10.1007\/s40471-017-0128-6.","journal-title":"Curr Epidemiol Rep"},{"issue":"5","key":"3000_CR26","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693\u20138. https:\/\/doi.org\/10.1038\/s41588-018-0099-7.","journal-title":"Nat Genet"},{"issue":"8","key":"3000_CR27","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/s0006-3223(98)00043-2","volume":"44","author":"F Curtin","year":"1998","unstructured":"Curtin F, Schulz P. Multiple correlations and Bonferroni\u2019s correction. Biol Psychiatry. 1998;44(8):775\u20137. https:\/\/doi.org\/10.1016\/s0006-3223(98)00043-2.","journal-title":"Biol Psychiatry"},{"key":"3000_CR28","doi-asserted-by":"publisher","first-page":"l2381","DOI":"10.1136\/bmj.l2381","volume":"366","author":"GJ Burton","year":"2019","unstructured":"Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381. https:\/\/doi.org\/10.1136\/bmj.l2381.","journal-title":"BMJ"},{"issue":"14","key":"3000_CR29","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1016\/j.jacc.2020.08.014","volume":"76","author":"CW Ives","year":"2020","unstructured":"Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia-Pathophysiology and Clinical presentations: JACC State-of-the-art review. J Am Coll Cardiol. 2020;76(14):1690\u2013702. https:\/\/doi.org\/10.1016\/j.jacc.2020.08.014.","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"3000_CR30","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1161\/hypertensionaha.118.12389","volume":"73","author":"K Kawasaki","year":"2019","unstructured":"Kawasaki K, Kondoh E, Chigusa Y, Kawamura Y, Mogami H, Takeda S, Horie A, Baba T, Matsumura N, Mandai M, et al. Metabolomic profiles of Placenta in Preeclampsia. Hypertension. 2019;73(3):671\u20139. https:\/\/doi.org\/10.1161\/hypertensionaha.118.12389.","journal-title":"Hypertension"},{"issue":"4","key":"3000_CR31","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrm3314","volume":"13","author":"GJ Patti","year":"2012","unstructured":"Patti GJ, Yanes O, Siuzdak G, Innovation. Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012;13(4):263\u20139. https:\/\/doi.org\/10.1038\/nrm3314.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3000_CR32","doi-asserted-by":"publisher","unstructured":"Kelly RS, Croteau-Chonka DC, Dahlin A, Mirzakhani H, Wu AC, Wan ES, McGeachie MJ, Qiu W, Sordillo JE, Al-Garawi A, et al. Integration of metabolomic and transcriptomic networks in pregnant women reveals biological pathways and predictive signatures associated with preeclampsia. Metabolomics. 2017;13(1). https:\/\/doi.org\/10.1007\/s11306-016-1149-8.","DOI":"10.1007\/s11306-016-1149-8"},{"key":"3000_CR33","doi-asserted-by":"publisher","first-page":"103177","DOI":"10.1016\/j.jri.2020.103177","volume":"141","author":"J Kikut","year":"2020","unstructured":"Kikut J, Komorniak N, Zi\u0119tek M, Palma J, Szczuko M. Inflammation with the participation of arachidonic (AA) and linoleic acid (LA) derivatives (HETEs and HODEs) is necessary in the course of a normal reproductive cycle and pregnancy. J Reprod Immunol. 2020;141:103177. https:\/\/doi.org\/10.1016\/j.jri.2020.103177.","journal-title":"J Reprod Immunol"},{"issue":"6","key":"3000_CR34","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/j.1600-0897.2010.00836.x","volume":"63","author":"G Mor","year":"2010","unstructured":"Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010;63(6):425\u201333. https:\/\/doi.org\/10.1111\/j.1600-0897.2010.00836.x.","journal-title":"Am J Reprod Immunol"},{"issue":"6","key":"3000_CR35","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1111\/cen.13003","volume":"84","author":"M Samimi","year":"2016","unstructured":"Samimi M, Jamilian M, Ebrahimi FA, Rahimi M, Tajbakhsh B, Asemi Z. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). 2016;84(6):851\u20137. https:\/\/doi.org\/10.1111\/cen.13003.","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"3000_CR36","doi-asserted-by":"publisher","first-page":"2228964","DOI":"10.1080\/14767058.2023.2228964","volume":"36","author":"H Zou","year":"2023","unstructured":"Zou H, Zou W, Li Q, Chen Z, Shi Y, Li C. Changes of gut mycobiota in the third trimester of pregnant women with preeclampsia. J Matern Fetal Neonatal Med. 2023;36(2):2228964. https:\/\/doi.org\/10.1080\/14767058.2023.2228964.","journal-title":"J Matern Fetal Neonatal Med"},{"key":"3000_CR37","doi-asserted-by":"publisher","first-page":"100118","DOI":"10.1016\/j.jlr.2021.100118","volume":"62","author":"B He","year":"2021","unstructured":"He B, Liu Y, Maurya MR, Benny P, Lassiter C, Li H, Subramaniam S, Garmire LX. The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia. J Lipid Res. 2021;62:100118. https:\/\/doi.org\/10.1016\/j.jlr.2021.100118.","journal-title":"J Lipid Res"},{"issue":"4","key":"3000_CR38","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1194\/jlr.P064451","volume":"57","author":"S Anand","year":"2016","unstructured":"Anand S, Young S, Esplin MS, Peaden B, Tolley HD, Porter TF, Varner MW, D\u2019Alton ME, Jackson BJ, Graves SW. Detection and confirmation of serum lipid biomarkers for preeclampsia using direct infusion mass spectrometry. J Lipid Res. 2016;57(4):687\u201396. https:\/\/doi.org\/10.1194\/jlr.P064451.","journal-title":"J Lipid Res"},{"issue":"3","key":"3000_CR39","doi-asserted-by":"publisher","first-page":"R364","DOI":"10.1152\/ajpregu.00115.2020","volume":"321","author":"M Gemmel","year":"2021","unstructured":"Gemmel M, Sutton EF, Brands J, Burnette L, Gallaher MJ, Powers RW. l-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia. Am J Physiol Regul Integr Comp Physiol. 2021;321(3):R364\u2013r376. https:\/\/doi.org\/10.1152\/ajpregu.00115.2020.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"12","key":"3000_CR40","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1111\/bph.15783","volume":"179","author":"AWC Man","year":"2022","unstructured":"Man AWC, Zhou Y, Lam UDP, Reifenberg G, Werner A, Habermeier A, Closs EI, Daiber A, M\u00fcnzel T, Xia N, et al. l-Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia. Br J Pharmacol. 2022;179(12):3007\u201323. https:\/\/doi.org\/10.1111\/bph.15783.","journal-title":"Br J Pharmacol"},{"issue":"3","key":"3000_CR41","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1590\/2175-8239-jbn-2018-0214","volume":"42","author":"ALF Fernandes","year":"2020","unstructured":"Fernandes ALF, Borges NA, Black AP, Anjos JD, Silva GSD, Nakao LS, Mafra D. Dietary intake of tyrosine and phenylalanine, and p-cresyl sulfate plasma levels in non-dialyzed patients with chronic kidney disease. J Bras Nefrol. 2020;42(3):307\u201314. https:\/\/doi.org\/10.1590\/2175-8239-jbn-2018-0214.","journal-title":"J Bras Nefrol"},{"key":"3000_CR42","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1111\/j.1651-2227.1994.tb13461.x","volume":"407","author":"HC Lou","year":"1994","unstructured":"Lou HC. Dopamine precursors and brain function in phenylalanine hydroxylase deficiency. Acta Paediatr Suppl. 1994;407:86\u20138. https:\/\/doi.org\/10.1111\/j.1651-2227.1994.tb13461.x.","journal-title":"Acta Paediatr Suppl"},{"key":"3000_CR43","doi-asserted-by":"publisher","first-page":"3546294","DOI":"10.1155\/2019\/3546294","volume":"2019","author":"WN Phoswa","year":"2019","unstructured":"Phoswa WN. Dopamine in the pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as possible mechanisms. Oxid Med Cell Longev. 2019;2019:3546294. https:\/\/doi.org\/10.1155\/2019\/3546294.","journal-title":"Oxid Med Cell Longev"},{"key":"3000_CR44","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.preghy.2022.01.003","volume":"27","author":"F Guo","year":"2022","unstructured":"Guo F, Yuan P, Long W, Yang Y, Yu B, Xue P. Alterations in the metabolic status of amino acids in newborns of pre-eclampsia women. Pregnancy Hypertens. 2022;27:170\u20132. https:\/\/doi.org\/10.1016\/j.preghy.2022.01.003.","journal-title":"Pregnancy Hypertens"},{"key":"3000_CR45","doi-asserted-by":"publisher","unstructured":"Prameswari N, Irwinda R, Wibowo N, Saroyo YB. Maternal amino acid status in severe preeclampsia: a cross-sectional study. Nutrients. 2022;14(5). https:\/\/doi.org\/10.3390\/nu14051019.","DOI":"10.3390\/nu14051019"},{"key":"3000_CR46","doi-asserted-by":"publisher","unstructured":"Srinivasan S, Torres AG, Ribas de Pouplana L. Inosine in Biology and Disease. Genes (Basel). 2021;12(4). https:\/\/doi.org\/10.3390\/genes12040600.","DOI":"10.3390\/genes12040600"},{"issue":"7","key":"3000_CR47","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/sj.sc.3101878","volume":"44","author":"F Liu","year":"2006","unstructured":"Liu F, You SW, Yao LP, Liu HL, Jiao XY, Shi M, Zhao QB, Ju G. Secondary degeneration reduced by inosine after spinal cord injury in rats. Spinal Cord. 2006;44(7):421\u20136. https:\/\/doi.org\/10.1038\/sj.sc.3101878.","journal-title":"Spinal Cord"},{"issue":"5","key":"3000_CR48","doi-asserted-by":"publisher","first-page":"E940","DOI":"10.1152\/ajpendo.00173.2005","volume":"290","author":"R Guinzberg","year":"2006","unstructured":"Guinzberg R, Cort\u00e9s D, D\u00edaz-Cruz A, Riveros-Rosas H, Villalobos-Molina R, Pi\u00f1a E. Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors. Am J Physiol Endocrinol Metab. 2006;290(5):E940\u201351. https:\/\/doi.org\/10.1152\/ajpendo.00173.2005.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"5","key":"3000_CR49","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.cjca.2020.02.066","volume":"36","author":"AA da Silva","year":"2020","unstructured":"da Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE. Role of Hyperinsulinemia and Insulin Resistance in hypertension: metabolic syndrome revisited. Can J Cardiol. 2020;36(5):671\u201382. https:\/\/doi.org\/10.1016\/j.cjca.2020.02.066.","journal-title":"Can J Cardiol"},{"issue":"2","key":"3000_CR50","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1111\/febs.15745","volume":"289","author":"M Hu","year":"2022","unstructured":"Hu M, Li J, Baker PN, Tong C. Revisiting preeclampsia: a metabolic disorder of the placenta. Febs j. 2022;289(2):336\u201354. https:\/\/doi.org\/10.1111\/febs.15745.","journal-title":"Febs j"},{"issue":"5\u20136","key":"3000_CR51","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.thromres.2004.06.038","volume":"114","author":"NM Gude","year":"2004","unstructured":"Gude NM, Roberts CT, Kalionis B, King RG. Growth and function of the normal human placenta. Thromb Res. 2004;114(5\u20136):397\u2013407. https:\/\/doi.org\/10.1016\/j.thromres.2004.06.038.","journal-title":"Thromb Res"},{"issue":"1","key":"3000_CR52","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1093\/oxfordjournals.humrep.a137028","volume":"5","author":"AL Gott","year":"1990","unstructured":"Gott AL, Hardy K, Winston RM, Leese HJ. Non-invasive measurement of pyruvate and glucose uptake and lactate production by single human preimplantation embryos. Hum Reprod. 1990;5(1):104\u20138. https:\/\/doi.org\/10.1093\/oxfordjournals.humrep.a137028.","journal-title":"Hum Reprod"},{"issue":"4","key":"3000_CR53","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/bies.201400155","volume":"37","author":"DK Gardner","year":"2015","unstructured":"Gardner DK. Lactate production by the mammalian blastocyst: manipulating the microenvironment for uterine implantation and invasion? BioEssays. 2015;37(4):364\u201371. https:\/\/doi.org\/10.1002\/bies.201400155.","journal-title":"BioEssays"},{"issue":"3","key":"3000_CR54","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1080\/10641950701436073","volume":"26","author":"E Turner","year":"2007","unstructured":"Turner E, Brewster JA, Simpson NA, Walker JJ, Fisher J. Plasma from women with preeclampsia has a low lipid and ketone body content\u2013a nuclear magnetic resonance study. Hypertens Pregnancy. 2007;26(3):329\u201342. https:\/\/doi.org\/10.1080\/10641950701436073.","journal-title":"Hypertens Pregnancy"},{"issue":"9","key":"3000_CR55","doi-asserted-by":"publisher","first-page":"21520","DOI":"10.3390\/ijms160921520","volume":"16","author":"M Austdal","year":"2015","unstructured":"Austdal M, Tanger\u00e5s LH, Skr\u00e5stad RB, Salvesen K, Austgulen R, Iversen AC, Bathen TF. First Trimester urine and serum metabolomics for prediction of Preeclampsia and Gestational Hypertension: a prospective screening study. Int J Mol Sci. 2015;16(9):21520\u201338. https:\/\/doi.org\/10.3390\/ijms160921520.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"3000_CR56","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s40272-020-00384-5","volume":"22","author":"J Rashid","year":"2020","unstructured":"Rashid J, Kumar SS, Job KM, Liu X, Fike CD, Sherwin CMT. Therapeutic potential of Citrulline as an arginine supplement: a clinical Pharmacology Review. Paediatr Drugs. 2020;22(3):279\u201393. https:\/\/doi.org\/10.1007\/s40272-020-00384-5.","journal-title":"Paediatr Drugs"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-024-03000-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-024-03000-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-024-03000-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T11:04:14Z","timestamp":1712315054000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcwomenshealth.biomedcentral.com\/articles\/10.1186\/s12905-024-03000-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3000"],"URL":"https:\/\/doi.org\/10.1186\/s12905-024-03000-7","relation":{},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,5]]},"assertion":[{"value":"22 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The GWAS summary data were derived from publicly available datasets and therefore did not require additional ethical approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declared they have no potential conflicts.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"223"}}