Metabolomics reveals pre-eclamptic-protective mechanisms within individuals

Pre-eclampsia is a common and dangerous hypertensive pregnancy complication, with recurrence in as many as 80% of subsequent pregnancies. However, it is often difficult to predict recurrence. Further complicating risk assessment and biomarker development, the genetic and environmental drivers of pre-eclampsia are varied and numerous. In this study, a longitudinal, repeated-measures design was used to control for many of these drivers, and to isolate factors that may be associated with pre-eclampsia in subsequent pregnancies.

In an exploratory cohort (n = 14) of individuals who had a pregnancy affected by pre-eclampsia and then had an immediate subsequent pregnancy without pre-eclampsia, late-gestation circulating metabolomics were evaluated utilizing a targeted (83 analytes) metabolomics profiling approach. Metabolites were extracted from maternal plasma samples collected from successive pregnancies.

Derivatized samples were analysed by gas chromatography-mass spectroscopy, and metabolites were identified and annotated in accordance with reference standards. All data were normalized ratiometrically and scaled uniformly.

Exploratory comparisons of pre-eclamptic and non-pre-eclamptic pregnancies revealed significant differences in inositol, methyl citrate, gamma-aminobutyric acid (GABA) and cysteine levels. Metabolite set quantitative enrichment analysis showed that pyruvate metabolism was potentially enriched among metabolites changed by pre-eclamptic status.

These findings demonstrate that metabolomic changes within individuals may biomark subsequent risk for pre-eclampsia, and specific metabolites may prove to be successful targets for future studies of pre-eclamptic therapeutics.