This work describes an exploratory NMR metabonomic study of second trimester maternal urine and plasma, in an attempt to characterize the metabolic changes underlying prenatal disorders and identify possible early
biomarkers.
Fetal malformations have the strongest metabolic impact in both biofluids, suggesting effects due to
hypoxia (leading to
hypoxanthine increased excretion) and a need for enhanced gluconeogenesis, with higher
ketone bodies (
acetone and
3-hydroxybutyric acid) production and TCA cycle demand (suggested by glucogenic
amino acids and cis-
aconitate overproduction).
Choline and
nucleotide metabolisms also seem affected and a distinct plasma
lipids profile is observed for mothers with fetuses affected by central nervous system malformations. Urine from women who subsequently develop
gestational diabetes mellitus exhibits higher 3-hydroxyisovalerate and
2-hydroxyisobutyrate levels, probably due to altered
biotin status and
amino acid and/or gut metabolisms (the latter possibly related to higher BMI values). Other urinary changes suggest
choline and
nucleotide metabolic alterations, whereas lower plasma
betaine and
TMAO levels are found.
Chromosomal disorders and pre-preterm delivery groups show urinary changes in
choline and, in the latter case, in
2-hydroxyisobutyrate. These results show that NMR metabonomics of maternal biofluids enables the noninvasive detection of metabolic changes associated to prenatal disorders, thus unveiling potential disorder
biomarkers.