Abstract
During pregnancy, dysbiosis in the vaginal microbiota directly affects the metabolic profiles, which might impact preterm birth (PTB). In this study, we performed cervicovaginal fluid (CVF) metabolic profiling using nuclear magnetic resonance (NMR) spectroscopy and identified the metabolic markers for predicting PTB. In this nested case-control study, 43 South Korean pregnant women with PTB (n = 22), and term birth (TB; n = 21) were enrolled with their demographic profiles, and CVF samples were collected by vaginal swabs. The PTB group had two subgroups based on post-CVF sampling birth: PTB less than (PTB < 7 d) and more than 7 days (PTB ≥ 7 d). We observed significant differences in the gestational age at birth (GAB), cervical length (CL), and neonatal birth weight among the groups. The principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA) scatter plot showed the separation between the PTB < 7 d group, and the TB group. Out of 28 identified metabolites, acetone, ethanol, ethylene glycol, formate, glycolate, isopropanol, methanol, and trimethylamine N-oxide (TMAO) were significantly increased in the PTB group compared with the TB group. The ROC curve analysis revealed that the acetone, ethylene glycol, formate, glycolate, isopropanol, methanol, and TMAO had the best predictive values for PTB. Additionally, the correlation analysis of these metabolites showed a strong negative correlation with GAB and CL. These metabolites could be beneficial markers for the clinical application of PTB prediction.
Highlights
Preterm birth (PTB), which is defined as the birth of a fetus in less than 37 weeks of the gestation period, is a serious problem of the neonate and maternal health with the risk of mortality and morbidity [1,2,3,4]
No statistical difference was observed in the women’s age, the pre-body mass index, gestational age at sampling (GAS), and blood parameters (WBC: white blood cell, and CRP: C-reactive protein) in the PTB group compared with the TB group (Table 1)
This study characterized the cervicovaginal fluid (CVF) metabolite profiles in symptomatic and asymptomatic pregnant women at the mid-gestation period using 1 H-nuclear magnetic resonance (NMR) spectroscopy. This is the first study about the association of CVF metabolites and PTB in Korean pregnant women
Summary
Preterm birth (PTB), which is defined as the birth of a fetus in less than 37 weeks of the gestation period, is a serious problem of the neonate and maternal health with the risk of mortality and morbidity [1,2,3,4]. 15 million cases of PTB are registered annually, and this number is continuously rising all over the world [5]. Poor conditions of the medical, social, economic and differences in ethnicity are prime factors of PTB [6]. Metabolites 2020, 10, 349 analysis [7,8]. These measures merely offer superficial information, and are inadequate for the confirmation of the PTB-causing agent. Reliability, accuracy, and data availability are questionable for PTB prediction
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