Metabolic dysfunction in pregnancy: Fingerprinting the maternal metabolome using proton nuclear magnetic resonance spectroscopy

Abstract

Aims: Maternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long-term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre-GDM), compared to controls.

Methods and materials: Second trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with ¹H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation.

Results: Obesity and pre-GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre-GDM. The three most impacted metabolites for the comparison of obesity versus pre-GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM.

Conclusion: These findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk.

Keywords: APrON study; biomarker; body mass index; gestational diabetes mellitus; maternal health; metabolomics; nmr spectroscopy; nuclear magnetic resonance; obesity; pathway analysis; personalized medicine; pregnancy; preterm birth; urine.