Amniotic Fluid Metabolomic Analysis in Spontaneous Preterm Birth

Abstract

Objective: To identify metabolic changes associated with early spontaneous preterm birth (PTB; <34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population. Method: In this study, AF samples retrieved from spontaneous PTB (<34 weeks [n ¼ 25]) and normal term birth (n ¼ 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Biochemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy. Results: Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (1) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB. Conclusion: Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be developmentally related and its contribution PTB as a cause or effect of PTB is still unclear.

Application of metabolomics in autoimmune diseases: Insight into biomarkers and pathology

“…The most biological specimens employed in metabolomics are serum/plasma (Kim et al, 2013), urine (Dieme et al, 2014), saliva (Santone et al, 2014), cerebrospinal fluid (Lista et al, 2014), bile (Nagana Gowda et al, 2009), seminal fluid (Kumar et al, 2014), amniotic fluid (Menon et al, 2014), synovial fluid (Giera et al, 2012), exhaled breath condensate (Leung et al, 2013), tissue extract (Wu et al, 2008), blister and cyst fluids (Hosch et al, 2008), fecal extracts (Walker et al, 2014), dialysis fluids (Qi et al, 2011), as well as tissue biopsy samples and their lipid and aqueous extract, such as from vascular tissue in studies of atherosclerosis (Martinez-Pinna et al, 2010). In the fields of autoimmune diseases, the common specimens are serum/plasma, urines, fecal extracts, and different tissue extracts or biological fluids according to different autoimmune diseases affecting different organ systems.…”

Measurement of amniotic fluid steroids of midgestation via LC–MS/MS

“…33 Wudy et al [17] were the first to publish gas-chromatographic 34 mass spectrometric (ID/GC-MS) reference data on the concen- 35 trations of steroids in amniotic fluid (AF) of midgestation. The 36 composition of AF changes with gestational age due to the progress 37 in fetal development [18]: during embryogenesis, AF composition 38 closely resembles fetal plasma. With further development of fetal 39 membranes and the placental barrier, free diffusion of AF occurs 40 between the fetus and the AF across the skin from 10-20 weeks of 41 gestation before the onset of skin keratinization thereafter.…”

“…1). While the focus of our study was the analysis of AF steroids, 392 recent studies sufficiently used mass-spectrometric analysis to 393 uncover the AF proteom [35] and to determine AF metabolomics 394 [36]. With applications of the MS method continuously expanding, 395 future fields of AF research are evolving.…”

Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring

“…In contrast, mothers with intraamniotic infection/inflammation had a more substantial decrease in compounds of the carbohydrate cluster, and a relative increase in amino acids. Menon et al [13] collected amniotic fluid from transvaginal amniocentesis samples taken prior to delivery during active labor in an African-American population and found that the global metabolite profiles differed significantly between normal and preterm birth. Many of the significantly altered metabolites in the PTB group reflected liver metabolism.…”

“…Metabolomics provides a powerful analytic tool to get insights into the complex interaction of genetics, environment and health and may serve to identify relevant predictive biomarkers for PTB. Previous work from Romero et al [12] and Menon et al [13] showed that the metabolomic profile of amniotic fluid is a good biomarker to assess the risk of preterm delivery. However, amniotic fluid sample collection is an invasive procedure with potential risk for adverse outcomes for both mother and child [14,15].…”