title: First-trimester prediction of preeclampsia using metabolomic biomarkers: a discovery phase study.
abstract: OBJECTIVE
  We tested the hypothesis that first-trimester metabolic biomarkers offered a unique profile in women with preeclampsia (PE) in the second half of pregnancy, compared with controls.
  
  
  METHODS
  We conducted a nested case-control study within a prospective cohort of pregnant women followed from the first-trimester to delivery. Cases were those who developed PE at any gestational age, and these were compared with a control group without adverse pregnancy outcome, matched for gestational age within 3 days. We analyzed maternal blood obtained at 11-14 weeks' gestation for 40 acylcarnitine species (C2-C18 saturated, unsaturated, and hydroxylated) and 32 amino acids by liquid chromatography tandem mass spectrometry. Logistic regression modeling estimated the association of each metabolite with development of PE.
  
  
  RESULTS
  We compared 41 cases with PE with 41 controls and found four metabolites (hydroxyhexanoylcarnitine, alanine, phenylalanine, and glutamate) that were significantly higher in the cases with PE. The area under the curve (AUC) using these metabolites individually to predict PE varied from 0.77 to 0.80, and when combined, the AUC improved to 0.82 [95% confidence interval (95% CI): 0.80-0.85] for all cases of PE and 0.85 (95% CI: 0.76-0.91) for early onset PE.
  
  
  CONCLUSIONS
  Our findings suggest a potential role for first-trimester metabolomics in screening for PE.
authors: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine and Ultrasound, Washington University in St. Louis, St. Louis, MO 63110, USA. odiboa@wudosis.wustl.edu
authors: Anthony O
authors: AO
authors: Odibo
authors: Katherine R
authors: KR
authors: Goetzinger
authors: Linda
authors: L
authors: Odibo
authors: Alison G
authors: AG
authors: Cahill
authors: George A
authors: GA
authors: Macones
authors: D Michael
authors: DM
authors: Nelson
authors: Dennis J
authors: DJ
authors: Dietzen
mesh_terms: D000328:Adult; D000409:Alanine / Q000097:blood; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D018698:Glutamic Acid / Q000097:blood; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D010649:Phenylalanine / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; C061301:hexanoylcarnitine; D018698:Glutamic Acid; D010649:Phenylalanine; D000409:Alanine; D002331:Carnitine