Cord blood metabolomic profiling in high risk newborns born to diabetic, obese, and overweight mothers: preliminary report.

OBJECTIVES

Newborns of diabetic and obese/overweight mothers face long-term metabolic risks. Untargeted cord blood metabolomic analysis using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) was performed to explore metabolic alterations and pathways in these high-risk infants.

METHODS

Cord blood samples were collected from 46 newborns born to mothers with gestational diabetes (10), obesity (14), overweight (18), type 2 diabetes mellitus (3), type 1 diabetes mellitus (1), and 20 newborns born to healthy mothers. Q-TOF LC/MS was used to investigate the alterations in cord blood metabolomic profiles. Data processing was conducted using MZmine 2.53. Putative metabolites were idendtified using MetaboAnalyst 6.0.

RESULTS

Distinct metabolite profiles were observed between diabetes and control groups. Significant identical trend in 19 metabolites were determined in both diabetes and obesity + overweight group vs. control group. Key pathways included steroid and bile acid biosynthesis. Upregulated oxidative stress, clues to sphingophospholipid metabolism, high levels of dihomo-gamma-linolenic acid (DGLA), pantothenic acid, and TRH were detected. The kynurenine pathway was prominent in the diabetes group.

CONCLUSIONS

Estrogen metabolites from the 16- and 2-pathways may indicate metabolic risk, with increased downstream flux under diabetic conditions. Accelerated bile acid synthesis may alter fetal metabolic programming, since bile acids play crucial roles in cellular energy regulation and signaling. Elevated pantothenic acid, essential for the production of coenzyme-A, suggests significant alterations in carbohydrate, protein, and fat metabolism. High serum DGLA levels emerge as a potential biomarker for metabolic abnormalities. Increased plasma kynurenines could predict cardiovascular risks. Larger targeted studies are required to validate these metabolic profiles and pathways.