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Published on: June 29, 2013
Insights into intrauterine growth restriction based on maternal and umbilical cord blood metabolomics
Georgios Moros1,2, Theodora Boutsikou3, Charalambos Fotakis2
1Department of Biochemistry & Biotechnology, University of Thessaly, Larisa, Greece.
Insights
Intrauterine growth restriction (IUGR) is linked to altered maternal and fetal metabolism, particularly amino acid imbalances. These metabolic changes in pregnant individuals with IUGR may indicate impaired nutrient transfer and increased insulin resistance.
Area of Science:
- Biochemistry
- Perinatal Medicine
- Metabolomics
Background:
- Intrauterine growth restriction (IUGR) presents significant challenges in fetal development due to limited maternal nutrient and oxygen supply.
- IUGR is associated with increased risks of fetal mortality, preterm birth, and postnatal complications.
Purpose of the Study:
- To investigate the metabolomic profiles in maternal and umbilical cord blood of pregnancies affected by IUGR.
- To identify specific metabolites and metabolic pathways altered in IUGR.
Main Methods:
- Untargeted 1H NMR metabolomics was employed on maternal and umbilical cord blood samples from IUGR and appropriate for gestational age (AGA) pregnancies.
- Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) was used for data analysis, followed by pathway and enrichment analysis.
Main Results:
- Distinct metabolomic profiles were observed in maternal and cord blood of IUGR pregnancies compared to AGA.
- Elevated levels of amino acids (alanine, leucine, valine, isoleucine, phenylalanine) were prominent in IUGR, suggesting impaired amino acid metabolism and transplacental flux.
- Lower glycerol levels indicated potential imbalances in gluconeogenesis and glycolysis, while elevated branched-chain amino acids correlated with increased insulin resistance.
Conclusions:
- Metabolomic analysis reveals significant alterations in maternal and fetal blood associated with IUGR.
- Impaired amino acid metabolism and potential insulin resistance are key features of IUGR pregnancies.
- Metabolomics offers insights into the complex pathophysiology of IUGR and potential biomarkers.
Abstract:
Intrauterine growth restriction (IUGR) is a fetal adverse condition, ascribed by limited oxygen and nutrient supply from the mother to the fetus. Management of IUGR is an ongoing challenge because of its connection with increased fetal mortality, preterm delivery and postnatal pathologies. Untargeted nuclear magnetic resonance (1H NMR) metabolomics was applied in 84 umbilical cord blood and maternal blood samples obtained from 48 IUGR and 36 appropriate for gestational age (AGA) deliveries. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) followed by pathway and enrichment analysis generated classification models and revealed significant metabolites that were associated with altered pathways. A clear association between maternal and cord blood altered metabolomic profile was evidenced in IUGR pregnancies. Increased levels of the amino acids alanine, leucine, valine, isoleucine and phenylalanine were prominent in IUGR pregnancies indicating a connection with impaired amino acid metabolism and transplacental flux. Tryptophan was individually connected with cord blood discrimination while 3-hydroxybutyrate assisted only maternal blood discrimination. Lower glycerol levels in IUGR samples ascribed to imbalance between gluconeogenesis and glycolysis pathways, suggesting poor glycolysis. The elevated levels of branched chain amino acids (leucine, isoleucine and valine) in intrauterine growth restricted pregnancies were linked with increased insulin resistance.
