title: Second trimester maternal urine for the diagnosis of trisomy 21 and prediction of poor pregnancy outcomes.
abstract: Given the recognized lack of prenatal clinical methods for the early diagnosis of preterm delivery, intrauterine growth restriction, preeclampsia and gestational diabetes mellitus, and the continuing need for optimized diagnosis methods for specific chromosomal disorders (e.g., trisomy 21) and fetal malformations, this work sought specific metabolic signatures of these conditions in second trimester maternal urine, using (1)H Nuclear Magnetic Resonance ((1)H NMR) metabolomics. Several variable importance to the projection (VIP)- and b-coefficient-based variable selection methods were tested, both individually and through their intersection, and the resulting data sets were analyzed by partial least-squares discriminant analysis (PLS-DA) and submitted to Monte Carlo cross validation (MCCV) and permutation tests to evaluate model predictive power. The NMR data subsets produced significantly improved PLS-DA models for all conditions except for pre-premature rupture of membranes. Specific urinary metabolic signatures were unveiled for central nervous system malformations, trisomy 21, preterm delivery, gestational diabetes, intrauterine growth restriction and preeclampsia, and biochemical interpretations were proposed. This work demonstrated, for the first time, the value of maternal urine profiling as a complementary means of prenatal diagnostics and early prediction of several poor pregnancy outcomes.
authors.affiliation: CICECO-Department of Chemistry, Campus Universitário de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sílvia O
authors.initials: SO
authors.lastname: Diaz
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
authors.forename: Eulália
authors.initials: E
authors.lastname: Galhano
authors.forename: Cristina
authors.initials: C
authors.lastname: Pita
authors.forename: Maria do Céu
authors.initials: Mdo C
authors.lastname: Almeida
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
mesh_terms: D016640:Diabetes, Gestational / Q000175:diagnosis* / Q000652:urine; D016002:Discriminant Analysis; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000652:urine; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D009421:Nervous System Malformations / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000652:urine; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000652:urine*; D047928:Premature Birth / Q000175:diagnosis* / Q000652:urine; D011296:Prenatal Diagnosis / Q000379:methods* / Q000706:statistics & numerical data