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

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 Participant: A secondary analysis of 2 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 (IQR) 12.4–13.7], 20 (IQR 19.3–23.0), and 28 (27.0–35.0) weeks of gestation. Results: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m²] in comparison to normal weight (BMI 18.5–24.99 kg/m²) 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 nonsignificant after adjustment for BMI and the other pregnancy disorders. 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.