1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

Abstract

BackgroundAdequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth.MethodologyThe metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates.Principal FindingsClear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood.ConclusionThese results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants.

Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study

“…Previous metabonomic studies corroborate our results, although on a smaller sample scale, where a general decrease of amino acids in maternal urine at gestational weeks 14–26 was observed in FGR cases ( n  = 10) compared to controls ( n  = 84) [9]. Significant differences in BCAA levels, along with other circulating amino acids, were also identified in plasma and cord blood studies of IUGR babies [8, 29]. The importance of BCAAs as predictive markers of gestational diabetes but also in non-pregnant populations of adiposity and type 2 diabetes is well established [27, 28, 30].…”

Urinary metabolic profiles in early pregnancy are associated with preterm birth and fetal growth restriction in the Rhea mother–child cohort study

“…The mechanisms relating N- acetyl glycoproteins to obesity and IPB, remain unclear; however, it is widely reported that high levels of adipose tissue can lead to systemic inflammation through release of cytokines such as interleukin-6, which could lead to an acute phase response [41]. Higher N- acetyl glycoprotein levels in NMR spectra of women with PB were also found in a study profiling maternal serum and cord blood at birth [42]. Spontaneous PB was specifically associated with higher urinary lysine, an essential amino acid that is limiting for growth, and is elevated in the plasma of premature infants [43].…”

Metabolomics in the developing infant

“…Subsequently, Tea et al [16] explored the metabolic adaptations associated with preterm birth using a NMR-based metabolomic approach. PCA showed clear distinctions between maternal and cord plasma of all samples.…”