Amniotic fluid metabolomic analysis in spontaneous preterm birth

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 = 25]) and normal term birth (n = 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. Bio-chemicals 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, (I) 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 devel-opmentally related and its contribution PTB as a cause or effect of PTB is still unclear.