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Discovery of novel metabolic signatures for early identification of women at risk of developing gestational hypertension

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Abstract

Introduction

Gestational hypertension (GH) is defined as the presence of systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, measured at least 4 h apart after 20 weeks of gestation. Early identification of women at high-risk of developing GH could contribute significantly towards improved maternal and fetal outcomes.

Objectives

To determine early metabolic biomarkers in women with GH as compared with normotensive women.

Methods

Serum samples were collected from subjects during three stages of their pregnancy: 8–12 weeks, 18–20 weeks and after 28 weeks (< 36 weeks) of gestation and studied using nuclear magnetic resonance (NMR) metabolomics approach. Multivariate and univariate analyses were performed to determine the significantly altered metabolites in GH women.

Results

A total of 10 metabolites, including isoleucine, glutamine, lysine, proline, histidine, phenylalanine, alanine, carnitine, N-acetyl glycoprotein and lactic acid were observed to be significantly downregulated during all pregnancy stages in women with GH as compared with controls. Furthermore, expression of 5 metabolites in the first trimester i.e., phenylalanine [area under the curve (AUC) = 0.745], histidine [AUC = 0.729], proline [AUC = 0.722], lactic acid [AUC = 0.722], and carnitine [AUC = 0.714] exhibited highest potential in discriminating GH from normotensive women.

Conclusion

The present study is the first of its kind to identify significantly altered metabolites that have the potential to discriminate between women at risk of developing GH and normotensive women across three trimesters of pregnancy. This opens up the possibility of exploring these metabolites as potential early predictive markers of GH.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

HDP:

Hypertensive disorders of pregnancy

GH:

Gestational hypertension

PIH:

Pregnancy-induced hypertension

ACOG:

American College of Obstetricians and Gynecologists

BP:

Blood pressure

NMR:

Nuclear magnetic resonance

MS:

Mass spectrometry

BMI:

Body mass index

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

OPLS-DA:

Orthogonal partial least squares discriminant analysis

HMDB:

Human metabolome database

MetPA:

Metabolomics pathway analysis

MSEA:

Metabolite set enrichment analysis

VIP:

Variable-importance in projection

ROC:

Receiver operating characteristic

AUC:

Area under the curve

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

    Sanjukta Dasgupta, Imon Mitra, Anindita Bhattacharya, Da Doma Sherpa & Koel Chaudhury

  2. Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA

    Elavarasan Subramani

  3. National Facility for High-field NMR, Tata Institute of Fundamental Research, Mumbai, India

    Mamata Joshi

  4. Institute of Reproductive Medicine, Salt Lake, Kolkata, India

    Pratip Chakraborty

  5. Department of Obstetrics & Gynaecology, Institute of Post Graduate Medical Education and Research (IPGMER) - SSKM Hospital, Kolkata, India

    Chaitali Datta Ray

Authors
  1. Sanjukta Dasgupta
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  3. Imon Mitra
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  9. Koel Chaudhury
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Contributions

The study was designed by SD, ES, PC, CD and KC. Experimentation and data analysis were performed by SD, ES, IM, AB, DS and MJ. The draft of the manuscript was written by SD and AB and reviewed by PC, CD and KC. All authors read and approved the final manuscript.

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Correspondence to Koel Chaudhury.

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All procedures performed were in accordance with the ethical standards of the institutional research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants included in the study.

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Dasgupta, S., Subramani, E., Mitra, I. et al. Discovery of novel metabolic signatures for early identification of women at risk of developing gestational hypertension. Metabolomics 19, 50 (2023). https://doi.org/10.1007/s11306-023-02012-y

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