{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:43:55Z","timestamp":1793148235098,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography\u2013mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features were significantly altered in EP plasma (p &lt; 0.05). Molecular networking and metabolite identification was employed using the Global Natural Products Social Molecular Networking (GNPS) database, which identified 97 metabolites at a high confidence level. Top significant metabolites include subclasses of sphingolipids, carnitines, glycerophosphocholines, and tryptophan metabolism. The top regression model, consisting of D-erythro-sphingosine and oleoyl-carnitine, was validated in a test group and achieved an area under receiving operating curve (AUC) (95% CI) = 0.962 (0.910\u20131) with a sensitivity of 100% and specificity of 95.9%. Metabolite alterations indicate alterations related to inflammation and abnormal placentation in EP. The validation of these metabolite biomarkers in the future could potentially result in improved early diagnosis.<\/jats:p>","DOI":"10.3390\/ijms251910333","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"10333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4286-7481","authenticated-orcid":false,"given":"Onur","family":"Turkoglu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Maternal Fetal Medicine Division, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Citil","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Zekai Tahir Burak Women\u2019s Health Education and Research Hospital, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1939-1334","authenticated-orcid":false,"given":"Ceren","family":"Katar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Zekai Tahir Burak Women\u2019s Health Education and Research Hospital, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Mert","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecological Oncology, Advocate Health, Chicago, IL 60642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-3256","authenticated-orcid":false,"given":"Robert A.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Michigan State University, Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray O.","family":"Bahado-Singh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Corewell Health, William Beaumont University Hospital, Royal Oak, MI 48073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-0002","authenticated-orcid":false,"given":"Stewart F.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Corewell Health, William Beaumont University Hospital, Royal Oak, MI 48073, USA"},{"name":"Metabolomics Department, Corewell Health Research Institute, William Beaumont University Hospital, Royal Oak, MI 48073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0140-6736(05)67103-6","article-title":"Ectopic pregnancy","volume":"366","author":"Farquhar","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0029-7844(96)00086-5","article-title":"Treatment of the small unruptured ectopic pregnancy: A cost analysis of methotrexate versus laparoscopy","volume":"88","author":"Alexander","year":"1996","journal-title":"Obstet. 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