Metabolomic profiling reveals key metabolic pathway alterations in monochorionic diamniotic twins with selective intrauterine growth restriction

Selective intrauterine growth restricted (sIUGR) is a major cause of stillbirth and adverse pregnancy outcomes in monochorionic diamniotic (MCDA) twins. However, the underlying pathophysiologic mechanism of sIUGR remains poorly understood. The study aims to investigate the metabolite perturbations and metabolic mechanisms of sIUGR fetuses through a metabolomics study. Umbilical cord blood was collected from 30 pairs of MCDA sIUGR twin fetuses and 11 pairs of MCDA preterm (PT) twins, followed by non-targeted metabolomics using gas chromatography-mass spectrometry. Data were further analyzed using partial least squares discriminant analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Spearman correlation analysis. Our results revealed significant metabolic differences in the umbilical cord blood among small for gestational age, appropriate for gestational age and PT fetuses, potentially linked to abnormalities in carbohydrate, amino acid, and lipid metabolism. A total of 156 metabolites were identified, of which 53 showed significant differences between the groups. Specifically, tryptophan levels were higher in the sIUGR group, while glutamic acid and palmitic acid levels were lower. Based on the KEGG enrichment analysis and the correlation analysis, we hypothesize that the tryptophan-indole metabolism pathway, which may impact immune regulation and neurodevelopment, requires further attention. Other key metabolic pathways, such as arginine metabolism and the citrate cycle were also altered. Our findings offer valuable insights into the biochemical disruptions associated with sIUGR. These results enhance our understanding of the metabolic mechanisms underlying sIUGR and pave the way for future research on potential diagnostic and therapeutic strategies.