Preeclampsia is a pregnancy-specific syndrome characterized by
hypertension and
proteinuria after 20 weeks of gestation. However, it is not well understood what
lipids are involved in the development of this condition, and even less is known how these
lipids mediate its formation. To reveal the relationship between
lipids and
preeclampsia, we conducted lipidomic profiling of maternal sera of 44 severe preeclamptic and 20 healthy pregnant women from a multiethnic cohort in Hawaii. Correlation network analysis showed that oxidized
phospholipids have increased intercorrelations and connections in
preeclampsia, whereas other
lipids, including
triacylglycerols, have reduced network correlations and connections. A total of 10
lipid species demonstrate significant changes uniquely associated with
preeclampsia but not any other clinical confounders. These species are from the
lipid classes of
lysophosphatidylcholines,
phosphatidylcholines (PCs),
cholesteryl esters,
phosphatidylethanolamines,
lysophosphatidylethanolamines, and
ceramides. A random forest classifier built on these
lipids shows highly accurate and specific prediction (F1 statistic = 0.94; balanced accuracy = 0.88) of severe
preeclampsia, demonstrating their potential as
biomarkers for this condition. These
lipid species are enriched in dysregulated biological pathways, including
insulin signaling, immune response, and phospholipid metabolism. Moreover, causality inference shows that various PCs and
lysophosphatidylcholines mediate severe
preeclampsia through PC 35:1e. Our results suggest that the lipidome may play a role in the pathogenesis and serve as
biomarkers of severe
preeclampsia.