The Exploration of Fetal Growth Restriction Based on Metabolomics: A Systematic Review

Abstract

Fetal growth restriction (FGR) is a common complication of pregnancy and a significant cause of neonatal morbidity and mortality. The adverse effects of FGR can last throughout the entire lifespan and increase the risks of various diseases in adulthood. However, the etiology and pathogenesis of FGR remain unclear. This study comprehensively reviewed metabolomics studies related with FGR in pregnancy to identify potential metabolic biomarkers and pathways. Relevant articles were searched through two online databases (PubMed and Web of Science) from January 2000 to July 2022. The reported metabolites were systematically compared. Pathway analysis was conducted through the online MetaboAnalyst 5.0 software. For humans, a total of 10 neonatal and 14 maternal studies were included in this review. Several amino acids, such as alanine, valine, and isoleucine, were high frequency metabolites in both neonatal and maternal studies. Meanwhile, several pathways were suggested to be involved in the development of FGR, such as arginine biosynthesis, arginine, and proline metabolism, glyoxylate and dicarboxylate metabolism, and alanine, aspartate, and glutamate metabolism. In addition, we also included 8 animal model studies, in which three frequently reported metabolites (glutamine, phenylalanine, and proline) were also present in human studies. In general, this study summarized several metabolites and metabolic pathways which may help us to better understand the underlying metabolic mechanisms of FGR.

Predicting the onset of preeclampsia by longitudinal monitoring of metabolic changes throughout pregnancy with Raman spectroscopy

“…Pathways associated with citric acid (TCA cycle; glyoxylate and dicarboxylate metabolism) also show a decreasing trend across pregnancy as observed in our Raman analysis (Figure 3o). These pathways are the main source of cellular energy; as the pregnancy advances, fetal and placental growth have a high energy demand resulting in depletion of maternal citric acid from 1st to 3rd trimester 63 …”

“…These pathways are the main source of cellular energy; as the pregnancy advances, fetal and placental growth have a high energy demand resulting in depletion of maternal citric acid from 1st to 3rd trimester. 63 Next, we examine which metabolic pathways are rewired in preeclampsia relative to healthy as patients' transition from 1st to 2nd trimester (Figure 4b), and then from 2nd to 3rd trimester (Figure 4c). Some enrichment ratios from the 1st to the 2nd trimester show a drastic increase in the preeclamptic cohort including multiple metabolic pathways associated with AAs such as glutamate, TCA cycle, fatty acid degradation, and nitrogen metabolism among others.…”

Cardiovascular prevention in childhood: a consensus document of the Italian Society of Cardiology Working Group on Congenital Heart Disease and Cardiovascular Prevention in Paediatric Age

“…Mitochondria provide the energy needed for cell function; accordingly, a reduction in numbers or functional alteration of mitochondria may damage cells, particularly those with a high energy demand, such as beta-pancreatic cells, endothelial cells, renal cells and cardiomyocytes, thus contributing to the onset of cardiometabolic diseases. Environmental and epigenetic factors may interact with genetic factors to affect uterine reprogramming of cells, resulting in remodelling at subcellular, tissue and organ levels with possible phenotypical fetal cardiac remodelling 17,18 …”

“…Environmental and epigenetic factors may interact with genetic factors to affect uterine reprogramming of cells, resulting in remodelling at subcellular, tissue and organ levels with possible phenotypical fetal cardiac remodelling. 17,18 Small for gestational age infants display high and early onset rates of hypertension (immature nephrogenesis results in the development of kidneys with a reduced number of filtrating units known as nephrons), stroke and diabetes in adulthood. [19][20][21][22] Also the prevalence of coronary artery disease is higher in these people than in their peers born with normal weight in the medium and long term.…”

Prediction of spontaneous preterm birth using supervised machine learning on metabolomic data: A case–cohort study

“…7 Metabolomics has shown potential to contribute to the improved prediction of various pathologies of pregnancy, such as pre-eclampsia, fetal growth restriction and gestational diabetes mellitus. [8][9][10][11][12] In addition, several studies have been published on the metabolomic prediction of sPTB or time to spontaneous labor. [12][13][14][15][16][17][18][19][20][21][22][23][24] However, metabolomics analyses involve complex data sets, with a vast number of predictors and relatively small sample sizes, known as the 'large p, small n problem'.…”