abstract
This paper describes a metabonomic study of prenatal disorders using nuclear magnetic resonance (NMR) spectroscopy of amniotic fluid (AF) collected in the second trimester of pregnancy, to search for metabolite markers of fetal malformations, prediagnostic gestational diabetes (GD), preterm delivery (PTD), early rupture of membranes (PROM), and chromossomopathies. Fetal malformations were found to have the highest impact on AF metabolite composition, enabling statistical validation to be achieved by several multivariate analytical tools. Results confirmed previous indications that malformed fetuses seem to suffer altered energy metabolism and kidney underdevelopment. Newly found changes (namely in a-oxoisovalerate, ascorbate, creatinine, isoleucine, serine, threonine) suggest possible additional effects on protein and nucleotide sugar biosynthesis. Prediagnostic GD subjects showed an average increase in glucose and small decreases in several amino acids along with acetate, formate, creatinine, and glycerophosphocholine. Small metabolite changes were also observed in the AF of subjects eventually undergoing PTD and PROM, whereas no relevant changes were found for chromossomopathies (for which a low number of samples was considered). The potential value of these results for biochemical insight and prediction of prenatal disorders is discussed, as well as their limitations regarding number of samples and overlap of different disorders.
keywords
FETAL LUNG MATURITY; NMR-SPECTROSCOPY; OXIDATIVE STRESS; MASS-SPECTROMETRY; PREGNANCIES; FETUSES; ACIDS
subject category
Biochemistry & Molecular Biology
authors
Graca, G; Duarte, IF; Barros, AS; Goodfellow, BJ; Diaz, SO; Pinto, J; Carreira, IM; Galhano, E; Pita, C; Gil, AM
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
António de Sousa Barros
Post-doc Fellowship
Brian James Goodfellow
Assistant Professor
Iola Melissa Fernandes Duarte
Principal Researcher
Joana Isabel Monteiro Pinto
Post-doc Fellowshipacknowledgements
The authors acknowledge the Foundation for Science and Technology, Portugal, for funding through research project PTDC/QUI/66523/2006 and grants SFRH/BD/41869/2007 and SFRH/BD/64159/2009. for GG and SD, respectively.