Maternal Plasma Metabolomic Profiles in Spontaneous Preterm Birth: Preliminary Results

Abstract

Objective To profile maternal plasma metabolome in spontaneous preterm birth. Method In this retrospective case-control study, we have examined plasma of patient with preterm birth (between 22 and 36 weeks of pregnancy (n = 57)), with threatened preterm labor (between 23 and 36 weeks of pregnancy (n = 49)), and with term delivery (n = 25). Plasma samples were analysed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in positive and negative polarity modes. Results We found 168 differentially expressed metabolites that were significantly distinct between study groups. We determined 51 metabolites using publicly available databases that could be subdivided into one of the five groups: amino acids, fatty acids, lipids, hormones, and bile acids. PLS-DA models, verified by SVM classification accuracy, differentiated preterm birth and term delivery groups. Conclusions Maternal plasma metabolites are different between term and preterm parturitions. Part of them may be related with preterm labor, while others may be affected by gestational age or the beginning of labor. Metabolite profile can classify preterm or term delivery groups raising the potential of metabolome as a biomarker to identify high-risk pregnancies. Metabolomic studies are also a tool to detect individual compounds that may be further tested in targeted researches.

Screening for Preterm Birth: Potential for a Metabolomics Biomarker Panel

“…4 of the top ranked features at 20 weeks were either putatively (Figures S24, S31, S39 in Supplementary Materials) or definitively (Figure S33 in Supplementary Materials) identified as Fatty Acids. Perturbed fatty acid levels have previously been reported as being associated with an increased risk of preterm birth and preterm labour [5,6,34,35,36].…”

“…We identified only one previous study in the literature using LCMS to investigate the serum metabolomic profiles of pregnant women who subsequently gave birth preterm [5], although that study only had 3 cases of preterm delivery that were not complicated by other pregnancy disorders. We identified one study investigating the plasma metabolomic profiles of pregnant women who gave birth preterm, however in that study samples were collected at the time of threatened preterm labour, not at an asymptomatic stage [6]. To our knowledge this is the first study investigating the metabolomics serum profiles of asymptomatic, uncomplicated (for any other reason) pregnancies that ended in spontaneous preterm birth.…”

Pregnancy lipidomic profiles and DNA methylation in newborns from the CHAMACOS cohort

“…This allowed for the discovery of novel associations between maternal metabolite levels, including phospholipids and lysolipids, and newborn DNA methylation, which could have implications on child health. Previous studies [28, 29] in pregnant women with poor birth outcomes compared to controls revealed differences in metabolomic profiles of lipid metabolites. In addition, lower levels of lysophospholipids, phospholipids, and monoacylglycerols during early pregnancy have been associated with macrosomia [30].…”

Association between phospholipid metabolism in plasma and spontaneous preterm birth: a discovery lipidomic analysis in the cork pregnancy cohort

“…Together, metabolites and lipids levels are regulated in response to environmental modifications (Goodacre et al 2004), and as such, are a direct reflection of the phenotype (Patti et al 2012); this makes them ideal candidates for biomarkers and therapeutic targets. Several recent studies have used metabolomics methods for biomarker discovery of PTB in plasma (Lizewska et al 2018), in amniotic fluid samples (Menon et al 2014;Romero et al 2010), and in cervicovaginal secretions (Auray-Blais et al 2011). A systematic review performed on the literature between 1965 and 2008 showed that various sample types have been used for the study of biomarkers of spontaneous preterm birth (Menon et al 2011), and 46.2% of included studies used maternal blood samples, 31.0% used amniotic fluid samples, and 1.2% used urine samples.…”