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Current clinical assays cannot predict the onset of preeclampsia until the late 2nd trimester, which often leads to poor maternal and neonatal outcomes. Here we show that Raman spectroscopy combined with machine learning in pregnant patient plasma enables rapid, highly sensitive maternal metabolome screening that predicts preeclampsia as early as the 1st trimester with &gt;82% accuracy. We identified 12, 15 and 17 statistically significant metabolites in the 1st, 2nd and 3rd trimesters, respectively. Metabolic pathway analysis shows multiple pathways corresponding to amino acids, fatty acids, retinol, and sugars are enriched in the preeclamptic cohort relative to a healthy pregnancy. Leveraging Pearson's correlation analysis, we show <jats:italic>for the first time<\/jats:italic> with Raman Spectroscopy that metabolites are associated with several clinical factors, including patients' body mass index, gestational age at delivery, history of preeclampsia, and severity of preeclampsia. We also show that protein quantification alone of proinflammatory cytokines and clinically relevant angiogenic markers are inadequate in identifying at\u2010risk patients. Our findings demonstrate that Raman spectroscopy is a powerful tool that may complement current clinical assays in early diagnosis and in the prognosis of the severity of preeclampsia to ultimately enable comprehensive prenatal care for all patients.<\/jats:p>","DOI":"10.1002\/btm2.10595","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T07:25:27Z","timestamp":1693466727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Predicting the onset of preeclampsia by longitudinal monitoring of metabolic changes throughout pregnancy with Raman spectroscopy"],"prefix":"10.1002","volume":"9","author":[{"given":"Saman","family":"Ghazvini","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering Iowa State University  Ames Iowa USA"},{"name":"Nanovaccine Institute Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saji","family":"Uthaman","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering Iowa State University  Ames Iowa USA"},{"name":"Nanovaccine Institute Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Synan","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering Iowa State University  Ames Iowa USA"},{"name":"Nanovaccine Institute Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene C.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry National Chung Cheng University  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumik","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Iowa state University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark K.","family":"Santillan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carver College of Medicine University of Iowa, Hospitals &amp; 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