Lipids serve as multifunctional metabolites that have important implications for the pregnant mother and developing fetus. Abnormalities in lipid metabolites have emerged as potential risk factors for pregnancy diseases, such as preeclampsia, and fetal growth restriction. The aim of this study was to assess the biomarker potential of lipid metabolites for early detection of pregnancy complications.
Plasma samples from the Biomarker and Ultrasound Measures for Preventable Stillbirth (BUMPS) cohort were collected at 36 weeks’ gestation, prior to diagnosis of fetal growth restriction (<5th birthweight centile, n=49), preeclampsia (n=17), both fetal growth restriction and preeclampsia (n=6), and gestation-matched controls (n=72). Analysis of maternal plasma was conducted by Metabolomics Australia and polar lipidomics was performed on the Agilent 6490 LC-QQQ mass spectrometer to quantify 468 lipids. MetaboAnalystR 3.2 was used for data pre-processing and MATLAB R2020b for statistical analysis.
Cholesterol esters (CE15:0, CE16:1, CE17:1, CE22:4, CE24:6) were significantly increased in maternal circulation of women who delivered fetal growth restriction babies at term (P<0.002, n=55 vs n=72 controls). Further analysis revealed cholesterol ester 17:1 provided the best predictive power for fetal growth restriction pregnancies (AUC=0.71). Phosphatidylinositol (P=0.0002), Phosphatidylcholine (P=0.0003), Diacylglycerol (P=0.0007) and Triacylglycerol (P=0.0008, n=23 vs n=72 controls) were the top dysregulated lipids in the maternal circulation of patients who later developed preeclampsia. Phosphatidylinositol was the best lipid to predict patients who developed preeclampsia later in pregnancy (AUC=0.81).
This study successfully quantified 468 lipids in maternal plasma collected from patients at 36 weeks’ gestation, who were later diagnosed with fetal growth restriction or preeclampsia later in pregnancy. The predictive capacity of generating lipid profiles for gestational disorders holds significant potential as a non-invasive assessment of maternal and fetal health. More studies are required to further investigate lipid metabolism in pregnancy and determine if lipid analysis provides a therapeutic window to treat gestational disorders.