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. 2020 Aug 17;10(1):13857.
doi: 10.1038/s41598-020-70974-3.

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

Hyo Kyozuka  1   2 , Toma Fukuda  3   4 , Tsuyoshi Murata  3   4 , Yuta Endo  3 , Aya Kanno  3 , Shun Yasuda  3 , Akiko Yamaguchi  3   4 , Miho Ono  3 , Akiko Sato  4 , Koichi Hashimoto  4 , Keiya Fujimori  3   4
Affiliations

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

Hyo Kyozuka et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Three metabolites that were significantly different between the control and Eo-HDP samples. (a) N,N-Dimethylglycine, (b) S-methylcysteine, (c) munic acid.
Figure 2
Figure 2
First trimester maternal serum metabolomic profiles of Eo-HDP-affected and healthy pregnancies. (a) PCA. Plots show the PCA scores obtained from maternal serum samples. Metabolically similar samples are located close to one other in the score plot. The x-axis indicates the main PC and the y-axis indicates the secondary PC. Each PC represents an axis in multidimensional space and corresponds to the direction of maximum variation in the original data. Numbers in parentheses indicate the contribution rates of each PC. (b): HCA. Rows and columns indicate metabolites and cases, respectively. Relative metabolite levels are represented in different colours, with red and green indicating increased and decreased levels, respectively.
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