The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

Ronde, E.; Reiss, Irwin K M; Hankemeier, Thomas; Meij, Tim G. de; Frerichs, Nina; Schoenmakers, Sam

doi:10.3389/fendo.2021.668417

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…Since the publication of our previous study, several additional articles have been published on the relationship between metabolic activity with BPD and its comorbidities, as referenced previously. Metabolomics have been used to investigate several other disease states relevant to the neonatal patient population as well (20)(21)(22)(23)(24). Our findings contribute to this growing exploration of the link between metabolism and variable treatment response in neonates as well as strengthen several of the findings we have published previously.…”

Section: Discussionsupporting

confidence: 82%

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia

et al. 2022

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Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response. Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort. A total of 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed with paired analysis of pre and post-treatment samples using Wilcoxon signed rank test. Correlation analysis was conducted between deltaRSS and pre-to-post change in metabolite level. Paired association analysis identified 20 plasma and 26 urine metabolites with significant level difference comparing pre to post treatment samples (p < 0.05). 4 plasma and 4 urine metabolites were also significant in the original study. Pre-to-post treatment change in metabolite analysis identified 4 plasma and 8 urine metabolites significantly associated with deltaRSS (p < 0.05). Change in urine citrulline levels showed a similar correlation pattern with deltaRSS in the first study, with increasing level associated with improved drug response. These results help validate the first major findings from pharmacometabolomics of BPD including key metabolites within the urea cycle and trans-4-hydroxyproline as a potential marker for lung injury. Ultimately, this study furthers our understanding of the mechanisms of steroid response in BPD patients and helps to design future targeted metabolomics studies in this patient population.

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Section: Discussionsupporting

confidence: 82%

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia

et al. 2022

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“…There are several major pathogenic mechanisms of PTB, including stress-induced activation of the fetal hypothalamic-pituitary-adrenal axis 5 , infections 6 , decidual hemorrhage 7 and pathologic uterine distention 8 . Metabolomics 9 , genetic and environmental factors 10 were also discussed as pathogenesis of PTB recently. Patients with PTB will face preterm complications, including neonatal mortality and morbidity, respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis 11 .…”

Section: Introductionmentioning

confidence: 99%

The abundances of LTF and SOD2 in amniotic fluid are potential biomarkers of gestational age and preterm birth

Hsu

Cheng

Lan

et al. 2023

Sci Rep

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Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance.

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“…The high-risk factors for premature birth include age, race, genetic factors, uterine factors, psychological factors, infection, smoking [8], history of premature birth, maternal nutrition, socio-economic background [1], etc. The main causes of premature birth include: reproductive tract infections [9][10][11], immune factors [8,12], and uterine factors [13]. Scholars such as Green and ES [9] have proposed that preterm birth is related to reproductive tract infections, but the use of antibiotics cannot improve outcomes, which may be related to early pregnancy infections.…”

Section: High Risk Factors and Etiology Of Premature Birthmentioning

confidence: 99%

Research Progress on the Relationship between Matrix Metalloproteinases and Preterm Birth

Yu,

2024

J Clin Med Res

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Premature birth is the main cause of death in children under the age of 5, and exploring the causes of premature birth has always been a hot research topic. Among them, matrix metalloproteinases (MMPS) have been confirmed to have a certain correlation with premature birth. This article summarizes the correlation between matrix metalloproteinases and preterm birth both domestically and internationally, in order to provide reference for subsequent research.

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The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

Cited by 6 publications

References 45 publications

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia

The abundances of LTF and SOD2 in amniotic fluid are potential biomarkers of gestational age and preterm birth

Research Progress on the Relationship between Matrix Metalloproteinases and Preterm Birth

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