Metabolic profiling of umbilical cord blood in macrosomia

Background/objective The term macrosomia is used to describe neonates with a birth weight of 4000 g or more. Macrosomia is a potential risk factor for obesity and metabolic syndromes in postnatal and adult life, yet little is known about its associations with metabolic difference in the early age. We performed metabolic profiling of umbilical cord blood to discover differential metabolites of macrosomia. Methods We conducted a case-control study of full-term singletons with normal maternal glucose tolerance [50 cases (macrosomia, birth weight ⩾4000 g); 50 controls (normal weight, birth weight 2500-3999 g)]. Metabolites in umbilical cord blood were detected using an untargeted metabolomic approach based on gas chromatography/mass spectrometry. We performed logistic regression to evaluate the associations between metabolites and macrosomia. We also performed pathway analysis based on KEGG and MBRole. Results Compared with controls, the macrosomia cases had a greater male proportion, gestational age, paternal body mass index (BMI) and maternal pre-pregnancy BMI. Forty-two metabolites differed between the cases and controls. After multivariable adjustment, 2-methylfumarate [adjusted odds ratio (AOR)=1.232, 95% confidence interval (CI): 1.102-1.376], uracil (AOR=38.494, 95% CI: 5.635-262.951), elaidic acid (AOR=0.834, 95% CI: 0.761-0.915), ribose (AOR=0.089, 95% CI: 0.021-0.378), lactulose (AOR=0.815, 95% CI: 0.743-0.894) and 4-aminobutyric acid (AOR=0.835, 95% CI: 0.764-0.912) remained significantly associated with macrosomia. Pyrimidine metabolism and pentose and glucuronate interconversions were the two top-ranking pathways enriched with those metabolites (-log P-value=3.49 and 2.47, respectively). Conclusion Levels of 2-methylfumarate, uracil, ribose, elaidic acid, lactulose and 4-aminobutyric acid were associated with the incidence of macrosomia. The alteration of pathways involving those factors might be linked with the incidence of macrosomia and relevant metabolic syndromes later in life, and further studies are needed to confirm it and verify the mechanisms.