Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Abstract

IntroductionPreterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles.ObjectivesWe sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB.MethodsA 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.ResultsSix 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.ConclusionHigh CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-0985-x) contains supplementary material, which is available to authorized users.

Differential vaginalLactobacillusspecies metabolism of glucose, L and D-lactate by13C-nuclear magnetic resonance spectroscopy

“…Vaginal bacterial communities dominated by L. jensenii usually have higher pH compared to when L. crispatus predominates (Aldunate et al ., 2015). We have previously observed that symptomatic women at risk of preterm birth show elevated cervicovaginal fluid acetate (Amabebe et al ., 2016a; Amabebe et al ., 2016b), which can be combined with pro-inflammatory mediators to improve its performance as a predictive marker (Amabebe et al ., 2019).…”

Vaginal metabolome: towards a minimally invasive diagnosis of microbial invasion of the amniotic cavity in women with preterm labor

“…A recent study reported the metabolic profile of women with and without BV using mass spectrometry-based metabolomics and classified women based on their vaginal metabolite composition 28 . Amabebe et al 29 www.nature.com/scientificreports www.nature.com/scientificreports/ hypothesized that the cervicovaginal ecosystem of commensal and pathogenic organisms could induce a specific metabolic profile that could be used for predicting the risk of PTD. In agreement with their previous report 29 , they demonstrated the potential of cervicovaginal acetate levels as a predictor of PTD using 1 H-NMR spectroscopy, especially in women with symptoms of PTL 30 .…”

Translational Systems Pharmacology Studies in Pregnant Women

“…Identification of biomarkers in maternal serum or plasma provides a less invasive approach to identify women at risk for PTB. Gunko et al . used mass spectrometric profiling of maternal serum to identify the proteomic predictors of PTB.…”

“…47 Identification of biomarkers in maternal serum or plasma provides a less invasive approach to identify women at risk for PTB. Gunko et al 48 used mass spectrometric profiling of maternal serum to identify the proteomic predictors of PTB. Their findings detected changes in the production of 25 proteins with various regulatory functions namely proteolysis, angiogenesis, inflammation processes, transcription, and binding and transportation of various ligands that can predict the PTB as early as during the second trimester of pregnancy.…”