Amniotic fluid and urine metabolomic alterations associated with pregnant women with Down syndrome fetuses

Down syndrome (DS) is a chromosomal disorder caused by a third copy of all or part of chromosome 21. Clinical observations and preclinical studies both suggest that DS may be associated with significant metabolic and bioenergetic alterations. But the metabolic alterations in pregnant women carrying DS fetuses still remains unclear. In this study, we investigated the characteristic metabolomics and lipidomics changes during fetal development of DS. The AF and random urine specimens were selected from 20 pregnant women carrying DS fetuses and 20 pregnant women carrying healthy fetuses. The diagnosis of DS was screened according to chromosome karyotype analysis, and untargeted metabolomic and lipidomic analyses were performed. Through the analyses of AF, 308 differential metabolites were selected between DS and controls. The metabolites with significant changes mainly involved lipid molecules, organic acids, nucleotides and carbon. Further analysis of lipidomics showed 64 differential metabolites, mainly involving glycerides, sphingolipids and glycerolipids. As for urine metabolomic and lipidomic analyses, there existed consistent metabolites with AF, but the number was much less. Compared with the controls, carbon metabolism, amino acid metabolism, glyceride metabolism, sphingolipid metabolism and glycerophospholipid metabolism were significantly changed in DS cases. In addition, characterized biomarkers in AF and urine were screened for DS diagnosis, and these metabolites were mainly involved in energy metabolism and liver dysfunction. This finding may help improve the efficiency of prenatal screening for DS.