Abstract: Objective To screen the specific metabolites associated with Trisomy 21 syndrome in the plasma of pregnant women,investigate the metabolic pathways and the pathogenesis of Trisomy 21,and guide the early screening and early diagnosis of high-risk population. Methods Pregnant women with normal karyotype or abnormal karyotype of Trisomy 21 syndrome were selected,and the components of serum metabolites were detected by UPLC-MS.Principal component analysis,Random forest analysis and Welch-t test were carried out to explore the specific metabolic markers and metabolic pathways related to Trisomy 21 syndrome. Results Thirtykinds of metabolic compounds were identified which strongly contributed to the variation between the normal group and the Trisomy 21 syndrome group,including tyramine sulfanilamide,N1,N12-diacetyl spermine,carboxyethyl gamma-aminobutyric acid,O-sulfo-L-tyrosine,pentose acid,2-Nring,aminophenol sulphate,etc.,and they were involved in amino acid metabolism,metabolism of sugar metabolism,lipid metabolism,polypeptide,nucleotide metabolism,heme metabolism and other metabolic pathways.All of these metabolic compounds were expected to become the potential metabolic markers of screening Trisomy 21 syndrome. Conclusion This study has successfully screened specific metabolic markers and metabolic pathways that may be related to Trisomy 21 syndrome,thus providing new ideas for clinical targeted early screening and early diagnosis of high-risk populations.