Background:
We examined whether the maternal metabolomic profile during pregnancy differed between lean and non-lean women with PMOS.
Methods:
Pregnant women with PMOS were identified within the Born in Bradford cohort and classified as having lean PMOS (body mass index [BMI] <25 kg/m²) or non-lean PMOS (BMI ≥25 kg/m²). Maternal serum metabolites and lipoprotein composition measures obtained during pregnancy were quantified using nuclear magnetic resonance metabolomics. Metabolites were log₂-transformed and analysed using separate linear regression models adjusted for maternal age. Results were expressed as the percentage difference in metabolite level in non-lean compared with lean PMOS and as standardised regression coefficients. Multiple testing was controlled using the Benjamini–Hochberg false discovery rate (FDR).
Results:
The analysis included 178 pregnant women with PMOS, of whom 60 had lean PMOS and 118 had non-lean PMOS. Fifteen of 34 metabolite measures remained significantly different after FDR correction. Glycerol showed the largest difference and was 22.6% higher in non-lean PMOS (95% CI 11.6–34.8%; standardised β=0.67; FDR P=0.001). Non-lean PMOS was also associated with higher XXL-VLDL free cholesterol percentage (14.9%, 95% CI 7.1–23.3%), lactate (13.0%, 95% CI 4.6–22.1%), β-hydroxybutyrate (10.2%, 95% CI 2.8–18.0%), XXL-VLDL phospholipid percentage (9.1%, 95% CI 3.5–14.9%) and creatinine (8.7%, 95% CI 3.8–13.8%). Triglyceride percentages within IDL and small, medium and large LDL particles were also higher in non-lean PMOS. Conversely, non-lean PMOS was associated with lower large-HDL free cholesterol percentage and lower cholesterol-related percentages in several large and XL-VLDL subclasses. Glucose and the measured amino acids did not differ after FDR correction.
Conclusion:
Among pregnant women with PMOS, the non-lean phenotype was associated with a distinct maternal metabolic profile characterised by increased lipid mobilisation, altered substrate utilisation and remodelling of triglyceride-rich lipoproteins. These differences may identify a metabolically higher-risk PMOS phenotype during pregnancy and warrant further investigation.