Untargeted Maternal Plasma Metabolomics in Hirschsprung Disease: A Pilot Study.

BACKGROUND AND AIMS: Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR.

METHODS: In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR ( n = 7) and age-matched mothers of normal children ( n = 6). The plasma metabolome was analyzed by ultra-high-pressure liquid chromatography and mass spectrometry. Metabolites were identified by mzCloud using Compound Discoverer software. Using an untargeted metabolomics workflow, metabolites with case versus control group differences were identified.

RESULTS: A total of 268 unique plasma metabolites were identified and annotated in maternal plasma. Of these, 57 were significantly different between case and control groups ( P < 0.05, t -test). Using a false discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19 metabolites were significantly different in HSCR cases, including carnitines, medium-chain fatty acids, and glutamic acid. Pathways affected were for amino acid and lipid metabolism.

CONCLUSION: Disordered prenatal metabolic pathways may be involved in the etiopathogenesis of HSCR in the developing fetus. This is the first study to assess maternal plasma metabolomics in HSCR.