Metabolomic identification of placental alterations in fetal growth restriction.

Ray O Bahado-Singh, Beaumont Health
Onur Turkoglu, Beaumont Health
Ali Yilmaz, Beaumont Health
Praveen Kumar, Beaumont Health
Amna Zeb, Beaumont Health
Shruti Konda
Eric Sherman
Joseph Kirma, Beaumont Health
Mathew Allos, Beaumont Health
Anthony Odibo
Dev Maulik
Stewart F Graham, Beaumont Health


Introduction: Fetal growth restriction (FGR), viz., birth weight metabolomics.Methods: Placenta samples from 19 FGR cases and 30 controls were analyzed using proton magnetic resonance (1H NMR) spectroscopy and direct flow injection mass spectrometry with reverse-phase liquid-chromatography mass spectrometry (DI-LC-MS/MS). Significant concentration differences (p-value Results: Of the 179 metabolites, 176 (98.3%) had reduced placental levels in FGR cases. The best performing metabolite model: 3-hydroxybutyrate, glycine and PCaaC42:0 achieved an AUC (95% CI) = 0.912 (0.814-1.000) with a sensitivity of 86.7% and specificity of 84.2% for FGR detection. Metabolite set enrichment analysis (MSEA) revealed significant (p < .05) perturbation of multiple placental metabolite pathways including urea metabolism, ammonia recycling, porphyrin metabolism, bile acid biosynthesis, galactose metabolism and perturbed protein biosynthesis.Conclusion: The placental metabolic pathway analysis revealed abnormalities that are consistent with fetal hepatic dysfunction in FGR. Near global reduction of metabolite concentrations was found in the placenta from FGR cases and metabolites demonstrated excellent diagnostic accuracy for FGR detection.