Longitudinal metabolic profiling of maternal obesity, gestational diabetes and hypertensive pregnancy disorders

Abstract
Context
Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden.

Objective
To assess levels, profiles and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM) or hypertensive disorders.

Design, Setting and Participants
A secondary analysis of two study cohorts, PREDO and RADIEL, including 741 pregnant women.

Main Outcome Measures
We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 (interquartile range, 12.4-13.7), 20 (19.3-23.0) and 28 (27.0-35.0) weeks of gestation.

Results
Across all three time points women with obesity (body mass index, BMI≥30kg/m 2) in comparison to normal weight (BMI 18.5-24.99 kg/m 2) had significantly higher levels of most very-low-density-lipoprotein-related measures, many fatty and most amino acids and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered non-significant after adjustment for BMI and the other pregnancy disorder.

Conclusions
This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.