title: Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy.
abstract: BACKGROUND
  Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles.
  
  
  OBJECTIVE
  We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB.
  
  
  METHODS
  A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20-22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20-22 g.w., n = 71, and 26-28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24-36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer.
  
  
  RESULTS
  Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62,p< 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20-22 g.w.) women (p= 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20-22 g.w.) (p= 0.048) and SYM (p= 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61-0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64-1) in the SYM women, whilst other metabolites were not.
  
  
  CONCLUSIONS
  High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.
authors.affiliation: Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Amabebe
authors.affiliation: Academic Unit of Radiology, Department of Cardiovascular Science, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Reynolds
authors.affiliation: Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stern
authors.affiliation: Integrated BioSciences, School of Clinical Dentistry, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Parker
authors.affiliation: Integrated BioSciences, School of Clinical Dentistry, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Stafford
authors.affiliation: Academic Unit of Radiology, Department of Cardiovascular Science, University of Sheffield, Sheffield, South Yorkshire UK.
authors.forename: Martyn N
authors.initials: MN
authors.lastname: Paley
authors.affiliation: Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, South Yorkshire UK ; Academic Unit of Reproductive and Developmental Medicine-Obstetrics and Gynecology, Department of Human Metabolism, University of Sheffield, 4th Floor, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF UK.
authors.forename: Dilly O C
authors.identifier: 0000-0003-2502-3033
authors.initials: DO
authors.lastname: Anumba
keywords: Cervicovaginal fluid; Metabolites; Nuclear magnetic resonance (NMR); Pregnancy; Preterm birth