Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction

Lucy A. Bartho; Daniel R. McKeating; Susan P. Walker; Brunda Nijagal; Teresa M. MacDonald; Natasha Pritchard; Natalie J. Hannan; Anthony V. Perkins; Stephen Tong; Tu’uhevaha J. Kaitu’u-Lino

doi:10.1038/s41598-024-65947-9

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Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction

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Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction

Lucy A. Bartho, Daniel R. McKeating, Susan P. Walker, Brunda Nijagal, Teresa M. MacDonald, Natasha Pritchard, Natalie J. Hannan, Anthony V. Perkins, Stephen Tong and Tu’uhevaha J. Kaitu’u-Lino

Scientific Reports, Vol.14, pp.1-11

2024

DOI: https://doi.org/10.1038/s41598-024-65947-9

PMID: 38982217

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Abstract

outcomes research

translational research

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks’ gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks’ gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia – increased L-cysteine (3.73-fold), L-cystine (3.28-fold), L-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant—including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term – reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant – including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.

Details

Title: Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction
Authors: Lucy A. Bartho (Corresponding Author) - The University of Melbourne
Daniel R. McKeating - Griffith University
Susan P. Walker - Mercy Hospital for Women
Brunda Nijagal - Griffith University
Teresa M. MacDonald - Mercy Hospital for Women
Natasha Pritchard - Mercy Hospital for Women
Natalie J. Hannan - The University of Melbourne
Anthony V. Perkins - Griffith University
Stephen Tong - Mercy Hospital for Women
Tu’uhevaha J. Kaitu’u-Lino - The University of Melbourne
Publication details: Scientific Reports, Vol.14, pp.1-11
Publisher: Nature Publishing Group
Date published: 2024
DOI: 10.1038/s41598-024-65947-9
ISSN: 2045-2322
PMID: 38982217
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Data Availability: Data available upon request. Contact Lucy Bartho for data information.
Grants: Purinergic signalling in placentation and vascular adaptation in pregnancy, FT210100193 , Australian Research Council (Australia, Canberra) - ARC
New diagnostics to predict preelampsia and fetal growth restriction, 1159261, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Translating new therapeutics and diagnostics for major pregnancy complications, 1136418, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Developing a Screening Test to Identify Women at Risk of Preeclampsia, 2000732, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Improving the prediction and detection of contributors to term stillbirth, 1065854, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Organisation Unit: School of Health
Language: English
Record Identifier: 991048995502621
Output Type: Journal article

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