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Metabolites
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Metabolic Profiles and Biomarkers in Pregnancy
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Metabolic Profiles and Biomarkers in Pregnancy

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (10 June 2023) | Viewed by 14130

Special Issue Editors

Prof. Dr. Antonio Ragusa

E-Mail Website
Guest Editor
1. Direttore U.O.C. Ostetricia e Ginecologia, Ospedale San Giovanni Calibita Fatebenefratelli, Isola Tiberina, 00186 Roma, Italy
2. Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, 00128 Rome, Italy
Interests: Obstetric; Metabolomic; heuristic cognitive psychology; environmental pollution, fetal pathology; evolution
Dr. Corrado Terranova

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, University ‘‘Campus Bio-Medico’’ of Rome, Via Alvaro del Portillo, 200-00128 Rome, Italy
Interests: gynecology; obstetrics; gynecology oncology; minimally invasive surgery; endocrinology; tumor biomarkers; human papilloma virus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolomics is one of the most promising "omics" sciences. It is a holistic technique, which tends to consider a series of complex factors, bringing them together in a whole that affects the cell and, ultimately, the individual. Metabolomics can study the metabolic complexity of cells, tissues, as well as of an entire organism. In practical terms, metabolomics, through the analysis of metabolites, allows analyzing the single final product of gene activation/inactivation, which in turn involves an activation/inactivation of the messenger RNA, which can set in motion the powerful enzymatic machine analyzed by the genome/proteome. It is therefore a question of evaluating the final metabolic product. In practice, any small molecule with a mass of less than 1 kD can be detected by metabolomic analysis. Since the metabolic product is influenced by the environment, metabolomic analysis allows an interesting intersection of information and allows analyzing the relationships between genotype and phenotype and intercorrelating this information. In normal and pathological pregnancy, metabolomics can unveil metabolic details and define normal and pathological metabolic trajectories of pregnancy.

In this Special Issue, we would like to focus on metabolomic changes in major obstetric syndromes in pregnancy and on the consequences of metabolic syndrome in pregnancy, and on the consequences of environmental pollution on the different metabolic profiles of pregnancy. This Special Issue will have five different sections:

1) Metabolomics and premature birth;

2) Metabolomics and metabolic syndrome;

3) Metabolomics and preeclampsia;

4) Metabolomics and diabetes;

5) Metabolomics and environmental pollution.

Prof. Dr. Antonio Ragusa
Prof. Dr. Corrado Terranova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics
  • biomarkers
  • pregnancy
  • premature birth
  • metabolic syndrome
  • preeclampsia
  • diabetes
  • environmental pollution

Published Papers (8 papers)

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Research

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16 pages, 1381 KiB  
Article
Pancreatic Beta Cell Function in Infants Varies by Maternal Weight
by Lisa R. Staimez, Anubrati Dutta, Yara S. Beyh, Ruby Gupta, Hari Krishna Noule, Vyakaranam Sapna, Kothapally Deepa, Aryeh D. Stein, K.M. Venkat Narayan, Dorairaj Prabhakaran, Basany Kalpana and Poornima Prabhakaran
Metabolites 2024, 14(4), 208; https://doi.org/10.3390/metabo14040208 - 06 Apr 2024
Viewed by 680
Abstract
The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18–35 years were recruited in Hyderabad, India. Women were classified by first trimester weight [...] Read more.
The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18–35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m2; normal weight (NW), BMI 18.5–22.9 kg/m2; or overweight (OW), BMI 23.0 through <28.5 kg/m2. At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (−64% median reduction) and changed the least in IOW (−7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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10 pages, 3135 KiB  
Article
Non-Targeted Metabolomic Study of Fetal Growth Restriction
by Fang Chen, Zhi Li, Yanwen Xu, Shuang Huang, Yanqiu Li and Weiying Jiang
Metabolites 2023, 13(6), 761; https://doi.org/10.3390/metabo13060761 - 17 Jun 2023
Cited by 1 | Viewed by 1683
Abstract
We aimed to explore the differential metabolites in amniotic fluid and its cells from fetuses with fetal growth restriction (FGR). A total of 28 specimens of amniotic fluid were collected, including 18 with FGR and 10 controls. Differential metabolites in all samples were [...] Read more.
We aimed to explore the differential metabolites in amniotic fluid and its cells from fetuses with fetal growth restriction (FGR). A total of 28 specimens of amniotic fluid were collected, including 18 with FGR and 10 controls. Differential metabolites in all samples were detected by chromatography–mass spectrometry. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to analyze the differences in metabolic spectra between the FGR and control groups through multidimensional and single-dimensional statistical analysis. The KEGG database was used for metabolic pathway enrichment analysis. Both PCA and OPLS-DA models showed a clear separation trend between FGR and control groups. We identified 27 differentially expressed metabolites in the amniotic fluid supernatant of the two groups (p < 0.05), of which 14 metabolites were up-regulated in the FGR group, and 13 metabolites, such as glutamate, phenylalanine, valine and leucine, were down-regulated. We also identified 20 differentially expressed metabolites in the amniotic fluid cell (p < 0.05), of which 9 metabolites, including malic acid, glycolic acid and D-glycerate, were up-regulated significantly and 11 metabolites, including glyceraldehyde, were down-regulated. Pathway analysis showed that most of the identified differential metabolites were involved in tricarboxylic acid cycle (TCA cycle), ABC transport, amino acid metabolism pathways and so on. The results indicated that many metabolic changes associated with FGR, which are mainly manifested by abnormal metabolism of amino acid in amniotic fluid and abnormal glucose metabolism including TCA cycle in amniotic fluid cells, respectively. Our findings provide more data for exploring the mechanism of FGR and the potential therapy targets. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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8 pages, 261 KiB  
Article
The sFlt-1/PlGF Ratio in Patients Affected by Gestational Diabetes and SARS-CoV-2 Infection
by Daniela Denis Di Martino, Chiara Maria Soldavini, Gabriele Rossi, Maria Chiara Lonardoni, Gabriele Tinè, Agnese Caneschi, Francesco D’Ambrosi and Enrico Ferrazzi
Metabolites 2023, 13(1), 54; https://doi.org/10.3390/metabo13010054 - 30 Dec 2022
Cited by 2 | Viewed by 1201
Abstract
Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia [...] Read more.
Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia from SARS-CoV-2 are characterized by an increased sFlt-1/PlGF ratio. The aim of the present study was to evaluate the sFlt-1-PlGF ratio in pregnancies complicated by COVID-19 and GD. We compared the plasmatic sFlt-1/PlGF ratio among the following groups of pregnant women: COVID-19, GD patients; COVID-19, non-GD patients; non-COVID-19, GD patients; and non-COVID-19, non-GD controls. We enrolled 62 women in the present study, who were divided as follows: 14 COVID-19, GD patients; 12 COVID-19, non-GD patients; 11 non-COVID-19, GD patients; and 25 non-COVID-19, non-GD controls. The COVID-19, GD patients presented a higher pre-pregnancy BMI, a higher prevalence of hypertensive disorders of pregnancy as a co-morbidity, and an increased need for medication for their diabetes. Neonatal data were similar between the groups. The controls showed a significantly lower sFlt-1/PlGF ratio compared to pregnancies complicated by GD and SARS-CoV-2 infection. The sFlt-1/PlGF ratio was higher in patients affected by both GD and SARS-CoV-2 infection; these subjects were characterized by a greater incidence of obesity and hypertensive disorders of pregnancy. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
16 pages, 1363 KiB  
Article
Maternal Metabolites Indicative of Mental Health Status during Pregnancy
by Katarina Laketic, Sophie Lalonde-Bester, Kim Smyth, Donna M. Slater, Suzanne C. Tough, Hiroaki Ishida, Hans J. Vogel, Gerald F. Giesbrecht, Chunlong Mu and Jane Shearer
Metabolites 2023, 13(1), 24; https://doi.org/10.3390/metabo13010024 - 23 Dec 2022
Cited by 5 | Viewed by 2066
Abstract
Approximately 25% of individuals report poor mental health during their pregnancy or postpartum period, which may impact fetal neurodevelopment, birth outcomes, and maternal behaviors. In the present study, maternal serum samples were collected from pregnancies at 28–32 weeks gestation from the All Our [...] Read more.
Approximately 25% of individuals report poor mental health during their pregnancy or postpartum period, which may impact fetal neurodevelopment, birth outcomes, and maternal behaviors. In the present study, maternal serum samples were collected from pregnancies at 28–32 weeks gestation from the All Our Families (Alberta, Canada) cohort and assessed using nuclear magnetic resonance spectroscopy (1H-NMR) and inductively coupled plasma-mass spectrometry (ICP-MS). Individuals with poor mental health at 34–36 weeks gestation were age-matched with mentally healthy pregnant controls. Metabolites were examined against validated self-reported mental health questionnaires for associations with depressive symptoms (Edinburgh Perinatal Depression Scale) and anxiety symptoms (Spielberger State-Trait Anxiety Inventory). 1H-NMR metabolites were identified for depression (alanine, leucine, valine, methionine, phenylalanine, glucose, lactate, 3-hydroxybutyrate, and pyruvate) and anxiety (3-hydroxybutyrate). For ICP-MS, antimony and zinc were significant for depression and anxiety, respectively. Upon false discovery rate (FDR) correction at 10%, five 1H-NMR metabolites (alanine, leucine, lactate, glucose, and phenylalanine) for depression remained significantly increased. Although results warrant further validation, the identified metabolites may serve as a predictive tool for assessing mental health during pregnancy as earlier identification has the potential to aid intervention and management of poor mental health symptomology, thus avoiding harmful consequences to both mother and offspring. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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13 pages, 779 KiB  
Article
Metabolome-Wide Associations of Gestational Weight Gain in Pregnant Women with Overweight and Obesity
by Jin Dai, Nansi S. Boghossian, Mark A. Sarzynski, Feng Luo, Xiaoqian Sun, Jian Li, Oliver Fiehn, Jihong Liu and Liwei Chen
Metabolites 2022, 12(10), 960; https://doi.org/10.3390/metabo12100960 - 11 Oct 2022
Cited by 2 | Viewed by 1469
Abstract
Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m [...] Read more.
Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m2. Untargeted metabolomic profiling was performed using fasting plasma samples collected at baseline (mean: 12.1 weeks) and 32 weeks of gestation. The associations of metabolites at each time point and changes between the two time points with GWG were examined by linear and least absolute shrinkage and selection operator (LASSO) regression analyses. Pearson correlations between the identified metabolites and cardiometabolic biomarkers were examined. Of the 769 annotated metabolites, 88 metabolites at 32 weeks were individually associated with GWG, with four (phosphatidylcholine (PC) 34:4, triacylglycerol (TAG) 52:6, arachidonic acid, isoleucine) jointly associated with GWG (area under the receiver operating characteristic curve (AUC) for excessive GWG: 0.80, 95% CI: 0.67, 0.93). No correlations were observed between the 88 metabolites and insulin, C-peptide, and high-sensitivity C-reactive protein at 32 weeks. Twelve metabolites at baseline (AUC for excessive GWG: 0.80, 95% CI: 0.62, 0.99) and three metabolite changes (AUC for excessive GWG: 0.73, 95% CI: 0.44, 1.00) were jointly associated with GWG. We identified novel metabolites in the first and third trimesters associated with GWG, which may shed light on the pathophysiology of GWG. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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Review

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14 pages, 279 KiB  
Review
Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives
by Marcello Cossu, Roberta Pintus, Marco Zaffanello, Michele Mussap, Fabiola Serra, Maria Antonietta Marcialis and Vassilios Fanos
Metabolites 2023, 13(3), 447; https://doi.org/10.3390/metabo13030447 - 18 Mar 2023
Cited by 1 | Viewed by 2064
Abstract
The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are [...] Read more.
The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
23 pages, 700 KiB  
Review
Childhood Obesity and the Cryptic Language of the Microbiota: Metabolomics’ Upgrading
by Alice Bosco, Michele Loi, Giulia Pinna, Roberta Pintus, Vassilios Fanos and Angelica Dessì
Metabolites 2023, 13(3), 414; https://doi.org/10.3390/metabo13030414 - 11 Mar 2023
Cited by 2 | Viewed by 1537
Abstract
The growing obesity epidemic in childhood is increasingly concerning for the related physical and psychological consequences, with a significant impact on health care costs in both the short and the long term. Nonetheless, the scientific community has not yet completely clarified the complex [...] Read more.
The growing obesity epidemic in childhood is increasingly concerning for the related physical and psychological consequences, with a significant impact on health care costs in both the short and the long term. Nonetheless, the scientific community has not yet completely clarified the complex metabolic mechanisms underlying body weight alterations. In only a small percentage of cases, obesity is the result of endocrine, monogenic, or syndromic causes, while in much more cases, lifestyle plays a crucial role in obesity development. In this context, the pediatric age appears to be of considerable importance as prevention strategies together with early intervention can represent important therapeutic tools not only to counteract the comorbidities that increasingly affect children but also to hinder the persistence of obesity in adulthood. Although evidence in the literature supporting the alteration of the microbiota as a critical factor in the etiology of obesity is abundant, it is not yet fully defined and understood. However, increasingly clear evidence is emerging regarding the existence of differentiated metabolic profiles in obese children, with characteristic metabolites. The identification of specific pathology-related biomarkers and the elucidation of the altered metabolic pathways would therefore be desirable in order to clarify aspects that are still poorly understood, such as the consequences of the interaction between the host, the diet, and the microbiota. In fact, metabolomics can characterize the biological behavior of a specific individual in response to external stimuli, offering not only an eventual effective screening and prevention strategy but also the possibility of evaluating adherence and response to dietary intervention. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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Other

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17 pages, 1181 KiB  
Systematic Review
The Exploration of Fetal Growth Restriction Based on Metabolomics: A Systematic Review
by Mengxin Yao, Zhuoqiao Yang, Xin Rong, Xuan Hu, Na Yao, Manting Zhu, Xinnan Wang, Xiaoyan Zhu and Jieyun Yin
Metabolites 2022, 12(9), 860; https://doi.org/10.3390/metabo12090860 - 13 Sep 2022
Cited by 5 | Viewed by 2385
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Metabolic Profiles and Biomarkers in Pregnancy)
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