Metabolic Characterization Of Amniotic Fluids Of Second-trimester Fetuses With Central Nervous System Isolated Ultrasonographic Soft Markers

Objective:To investigate the amino acid metabolic characterization of fetus central nervous system isolated ultrasonographic soft markers amniotic fluid obtained by ultrasoundguided amniocentesis.Methods:Ultrasound-guided amniocentesis was performed in 20 fetuses with Isolated Choroid Plexus Cyst(ICPC),12 fetuses with Isolated Ventriculomegaly(IVM)and 32 normal fetuses.The amniotic fluid of normal pregnancy was matched with the case samples in a 1:1 ratio based upon gestational age.Amniotic fluid of 64 fetuses was detected by Liquid Chromatography-Mass Spectrometry(LC-MS).Then the peaks area of metabolites were analyzed by Principal Component Analysis(PCA),Partial Least Square Discriminant Analysis(PLS-DA)and univariate statistical analysis.Results:1.The average gestational ages at amniocentesis of ICPC group and normal group1 were(152.4±19.3)days and(151.1±19.1)days,(P>0.05).The average gestational age at amniocentesis of IVM group and normal group 2 were(174.0±5.5)days and(172.9 ±5.4)days,(P>0.05).The average maternal ages of ICPC group and normal group 1 were(31.2±4.2)years and(32.4±6.3)years,(P>0.05).The average maternal ages of IVM group and normal group 2 were(30.2 ± 5.5)years and(28.2 ± 5.5)years,(P>0.05).2.A total of 31 amino acids were identified.3.Seven different amino acids screened out in ICPC group,included proline,5-hydroxylysine,lysine,valine,isoleucine,ethanolamine and leucine(P<0.05).Six different amino acids screened in IVM group,including: lysine,ornithine,aspartate,β-amino-isobutyric acid,proline,5-hydroxylysine(P<0.05).4.A total of 7 metabolic pathways were significantly altered in the ICPC group,including valine,leucine and isoleucine biosynthesis,valine,leucine and isoleucine degradation,lysine degradation,biotin metabolism,pantothenate and Co A biosynthesis,glycerophospholipid metabolism,and arginine and proline metabolism.A total of 8metabolic pathways were significantly altered in the IVM group,including arginine biosynthesis,lysine degradation,biotin metabolism,nicotinate and nicotinamide metabolism,pantothenate and Co A biosynthesis,β-alanine metabolism,arginine and proline metabolism,and glutathione metabolism.Conclusion:1.ICPC fetuses showed several altered metabolic pathways(valine,leucine and isoleucine biosynthesis,valine,leucine and isoleucine degradation,glycerophospholipid metabolism,arginine and proline metabolism,pantothenate and Co A biosynthesis)that suggest fetuses exist abnormal amino acid metabolism,and it may ultimately affect fetal glucose and lipid metabolism.2.IVM fetuses showed several altered metabolic pathways(β-alanine metabolism,arginine and proline metabolism,pantothenate and Co A biosynthesis,glutathione metabolism,nicotinate and nicotinamide metabolism)that suggest fetuses exist abnormal amino acid metabolism that may ultimately affect fetal energy metabolism.And it also suggests that oxidative stress may exist in the fetus.3.The results of this study indicated that lysine degradation and biotin metabolism pathways were significantly altered in ICPC or IVM fetuses.These pathways were closely related to the development of fetal nervous system,and providing a new idea for the production mechanism of ICPC or IVM.