The causal relationship between circulating metabolites and gestational hypertension, pre-eclampsia, eclampsia: A...

Area of Science:

• Metabolomics
• Genetics
• Obstetrics

Background:

• Gestational hypertension, pre-eclampsia, and eclampsia are major pregnancy risks with unclear origins.
• Understanding the metabolic underpinnings is crucial for improving maternal and fetal outcomes.

Purpose of the Study:

• To investigate the causal associations between 233 circulating metabolites and the risk of gestational hypertension, pre-eclampsia, and eclampsia.
• To identify potential metabolic biomarkers for these hypertensive disorders of pregnancy.

Main Methods:

• Utilized a bidirectional two-sample Mendelian randomization (MR) analysis on data from the GWAS database.
• Employed inverse variance weighting as the primary method, with MR-Egger, weighted median, and other methods for sensitivity analysis.
• Assessed robustness, heterogeneity, and horizontal pleiotropy through comprehensive sensitivity analyses.

Main Results:

• Reduced citrate levels were linked to increased gestational hypertension risk.
• Elevated conjugated linoleic acid to total fatty acids ratio correlated with higher risks of gestational hypertension and pre-eclampsia/eclampsia.
• Specific phospholipid and cholesterol ratios in lipoproteins (HDL, VLDL, chylomicrons) showed associations with pre-eclampsia/eclampsia risk.
• Reverse MR indicated reduced cholesteryl esters in VLDL and lower total choline/phosphoglycerides associated with gestational hypertension and pre-eclampsia/eclampsia, respectively.
• Sensitivity analyses confirmed the absence of significant heterogeneity or pleiotropy.

Conclusions:

• Established causal links between specific metabolites and hypertensive disorders of pregnancy.
• Identified potential metabolic targets and biomarkers for gestational hypertension, pre-eclampsia, and eclampsia.
• Findings may guide the development of novel clinical strategies for the diagnosis and management of these conditions.