Comprehensive metabolomic analysis of first-trimester serum identifies biomarkers of early-onset hypertensive disorder of pregnancy

Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children’s Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch’s t-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.