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

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.

SUBMITTER: Kyozuka H

PROVIDER: S-EPMC7431422 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Kyozuka Hyo H Fukuda Toma T Murata Tsuyoshi T Endo Yuta Y Kanno Aya A Yasuda Shun S Yamaguchi Akiko A Ono Miho M Sato Akiko A Hashimoto Koichi K Fujimori Keiya K

Scientific reports 20200817 1

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 ...[more]

PMID: 32807817

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Project description:Healthy pregnancy requires a coordinated immune response, yet complications can arise, putting both the mother's and child's health at risk. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are pregnancy-related complications that account for most maternal morbidity and mortality. Cytokines are proteins released as part of the immune response to disease or infection and regulate inflammation. Certain pregnancy complications cause localized and systemic inflammation; however, cytokine profiles specific to such complications are not well understood. This study aims to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Data was obtained from the All Our Families birth cohort in Calgary, Alberta, Canada. The cohort collected questionnaires at the time of participant enrollment and maternal blood samples at 17-23 weeks gestation. Cases of HDP (n = 27) and GDM (n = 31) were matched to controls on BMI, maternal age, and smoking status in the preconception period at a 1:3 ratio. Cytokine levels were measured in blood samples using Luminex xMAP technology using a panel of 42 cytokines. Using R software, a Classification and Regression Tree (CART) analysis was conducted to identify cytokine profiles and levels associated with each complication. Four cytokines were identified in the HDP CART (in descending order of importance): Monocyte Chemoattractant Protein-1 (cut-off: <480pg/mL), Macrophage Inflammatory Protein-1β (cut-off: ≥26pg/mL), Eotaxin (cut-off: <27/≥27&<36/≥36pg/mL), and Soluble Cluster of Differentiation 40 Ligand (cut-off: <1342pg/mL). Six cytokine levels were identified in the GDM CART: Interleukin-1 Receptor Antagonist (IL-1Ra; cut-off: <25pg/mL), Interleukin-5 (cut-off: ≥0.4pg/mL), Interferon-γ (cut-off: <4.9pg/mL), IL-1Ra (cut-off: ≥111pg/mL), Eotaxin (cut-off: ≥21pg/mL), and Interleukin-18 (cut-off: ≥155pg/mL). By examining the complex inter-relationships between cytokines, findings of cytokine profiles guide further research in identifying biomarkers of pregnancy complications relevant to the design of the future management or prevention of these conditions.

Dataset Information

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

Publications

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

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