Pregnancy is characterized by a complexity of metabolic processes that may
impact fetal development and ultimately, infant health outcomes. However, our
understanding of whole body maternal and fetal metabolism during this critical
life stage remains incomplete. The objective of this study is to utilize
metabolomics to profile longitudinal patterns of fasting maternal metabolites
among a cohort of non-diabetic, healthy pregnant women in order to advance our
understanding of changes in protein and lipid concentrations across gestation,
the biochemical pathways by which they are metabolized and to describe
variation in maternal metabolites between ethnic groups. Among 160 pregnant
women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies
and non-esterified fatty acids were detected by liquid chromatography coupled
with mass spectrometry, while polar lipids were detected through flow-injected
mass spectrometry. The maternal plasma concentration of several essential and
non-essential amino acids, long-chain polyunsaturated fatty acids, free
carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins
significantly decreased across pregnancy. Concentrations of several TCA
intermediates increase as pregnancy progresses, as well as the keto-body
β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of
metabolic pathways suggest a decreased beta-oxidation rate and increased
carnitine palmitoyltransferase-1 enzyme activity with advancing gestation.
Decreasing amino acid concentrations likely reflects placental uptake and
tissue biosynthesis. The absence of any increase in plasma non-esterified
fatty acids is unexpected in the catabolic phase of later pregnancy and may
reflect enhanced placental fatty acid uptake and utilization for fetal tissue
growth. While it appears that energy production through the TCA cycle
increases as pregnancy progresses, decreasing patterns of free carnitine and
acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and
β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to
ensure sufficient energy supply in the fasting state. Several differences in
metabolomic profiles between Hispanic and non-Hispanic women demonstrate
phenotypic variations in prenatal metabolism which should be considered in
future studies