title: Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies.
abstract: Physiologic concentration in amniotic fluid (AF) of several metabolites has not been established with certainty. In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring). Results allowed to determine physiologic reference intervals for 45 compounds. In these AF, not all purines and pyrimidines were detectable and uric acid (238.35±76.31 μmol/l) had the highest concentration. All amino compounds were measurable, with alanine having the highest concentration (401.10±88.47 μmol/l). In the second part of the study, we performed a blind metabolic screening of AF to evaluate the utility of this biochemical analysis as an additional test in amniocenteses. In 1,295 additional AF from normal pregnancies, all metabolites fell within the confidence intervals determined in the first part of the study. In 24 additional AF from women carrying Down's syndrome-affected fetuses, glutamate, glutamine, glycine, taurine, valine, isoleucine, leucine, ornithine, and lysine were different from physiologic reference values. One AF sample showed phenylalanine level of 375.54 μmol/l (mean value in normal AF=65.07 μmol/l) and was from a woman with unreported phenylketonuria with mild hyperphenylalaninemia (serum phenylalanine=360.88 μmol/l), carrying the IVS 4+5 G-T and D394A mutations. The fetus was heterozygote for the maternal D394A mutation. An appropriate diet maintained the mother phenylalanine in the range of normality during pregnancy, avoiding serious damage in fetal and neonatal development. These results suggest that the metabolic screening of AF might be considered as an additional biochemical test in amniocenteses useful to highlight anomalies potentially related to IEM.
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome Sacro Cuore, Largo F. Vito 1, 00164, Rome, Italy.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Amorini
authors.forename: Claudio
authors.initials: C
authors.lastname: Giorlandino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Longo
authors.forename: Serafina
authors.initials: S
authors.lastname: D'Urso
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mesoraca
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Santoro
authors.forename: Marika
authors.initials: M
authors.lastname: Picardi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gullotta
authors.forename: Pietro
authors.initials: P
authors.lastname: Cignini
authors.forename: Dario
authors.initials: D
authors.lastname: Lazzarino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lazzarino
authors.forename: Barbara
authors.initials: B
authors.lastname: Tavazzi
mesh_terms: D000588:Amines / Q000032:analysis; D000649:Amniocentesis / Q000379:methods*; D000653:Amniotic Fluid / Q000737:chemistry* / Q000378:metabolism; D004314:Down Syndrome; D005260:Female; D006801:Humans; D008403:Mass Screening; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism; D055442:Metabolome; D011247:Pregnancy; D011687:Purines / Q000032:analysis; D011743:Pyrimidines / Q000032:analysis
chemical_list: D000588:Amines; D011687:Purines; D011743:Pyrimidines