Editorial

4 pages, 179 KiB

Open AccessEditorial

Metabolomics Applications in Children: A Right Way to Go

by Maria Elisabetta Baldassarre and Nicola Laforgia

Metabolites 2020, 10(9), 364; https://doi.org/10.3390/metabo10090364 - 08 Sep 2020

Cited by 2 | Viewed by 1887

Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such [...] Read more.

Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such as hypoxic–ischemic encephalopathy (HIE), intrauterine growth restriction (IUGR), congenital infections, genetic diseases, neonatal nutrition. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

Research

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16 pages, 1789 KiB

Open AccessArticle

Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients

by Camilla Ceccarani, Giulia Bassanini, Chiara Montanari, Maria Cristina Casiraghi, Emerenziana Ottaviano, Giulia Morace, Giacomo Biasucci, Sabrina Paci, Elisa Borghi and Elvira Verduci

Metabolites 2020, 10(4), 133; https://doi.org/10.3390/metabo10040133 - 30 Mar 2020

Cited by 30 | Viewed by 3686

Abstract

A life-long dietary intervention can affect the substrates’ availability for gut fermentation in metabolic diseases such as the glycogen-storage diseases (GSD). Besides drug consumption, the main treatment of types GSD-Ia and Ib to prevent metabolic complications is a specific diet with definite nutrient [...] Read more.

A life-long dietary intervention can affect the substrates’ availability for gut fermentation in metabolic diseases such as the glycogen-storage diseases (GSD). Besides drug consumption, the main treatment of types GSD-Ia and Ib to prevent metabolic complications is a specific diet with definite nutrient intakes. In order to evaluate how deeply this dietary treatment affects gut bacteria, we compared the gut microbiota of nine GSD-I subjects and 12 healthy controls (HC) through 16S rRNA gene sequencing; we assessed their dietary intake and nutrients, their microbial short chain fatty acids (SCFAs) via gas chromatography and their hematic values. Both alpha-diversity and phylogenetic analysis revealed a significant biodiversity reduction in the GSD group compared to the HC group, and highlighted profound differences of their gut microbiota. GSD subjects were characterized by an increase in the relative abundance of Enterobacteriaceae and Veillonellaceae families, while the beneficial genera Faecalibacterium and Oscillospira were significantly reduced. SCFA quantification revealed a significant increase of fecal acetate and propionate in GSD subjects, but with a beneficial role probably reduced due to unbalanced bacterial interactions; nutritional values correlated to bacterial genera were significantly different between experimental groups, with nearly opposite cohort trends. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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16 pages, 1957 KiB

Open AccessArticle

Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes

by José David Piñeiro-Ramos, Antonio Núñez-Ramiro, Roberto Llorens-Salvador, Anna Parra-Llorca, Ángel Sánchez-Illana, Guillermo Quintás, Nuria Boronat-González, Juan Martínez-Rodilla, Julia Kuligowski, Máximo Vento and The HYPOTOP Study Group

Metabolites 2020, 10(3), 109; https://doi.org/10.3390/metabo10030109 - 14 Mar 2020

Cited by 15 | Viewed by 3322

Abstract

Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of [...] Read more.

Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of a cohort of 55 asphyxiated infants who evolved to moderate/severe HIE were collected between birth and completion of therapeutic hypothermia (TH). Samples were analyzed employing a quantitative gas chromatography–mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography–time-of-flight mass spectrometry method for metabolic fingerprinting. Brain injury was assessed employing magnetic resonance imaging (MRI). A critical assessment of the usefulness of lactate, pyruvate, and pyruvate/lactate for outcome prediction was carried out. Besides, metabolic fingerprinting identified a dynamic perturbation of eleven metabolic pathways, including amino acid and purine metabolism, and the steroid hormone biosynthesis, in newborns with pathologic MRI outcomes. Although data suggest the usefulness of lactate and pyruvate monitoring during 72 h for discerning outcomes, only the steroid hormone biosynthesis pathway was significantly altered in early plasma samples (i.e., before the initiation of TH). This study highlights pathways that might potentially be targeted for biomarker discovery or adjuvant therapies to be combined with TH. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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14 pages, 912 KiB

Open AccessArticle

¹H-NMR Urinary Metabolic Profile, A Promising Tool for the Management of Infants with Human Cytomegalovirus-Infection

by Marie Antoinette Frick, Ignasi Barba, Marina Fenoy-Alejandre, Paula López-López, Fernando Baquero-Artigao, Paula Rodríguez-Molino, Antoni Noguera-Julian, Marta Nicolás-López, Asunción de la Fuente-Juárez, Maria Gemma Codina-Grau, Juliana Esperalba Esquerra, Ángeles Linde-Sillo and Pere Soler-Palacín

Metabolites 2019, 9(12), 288; https://doi.org/10.3390/metabo9120288 - 25 Nov 2019

Cited by 6 | Viewed by 2638

Abstract

Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to [...] Read more.

Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (¹H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p < 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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Review

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19 pages, 267 KiB

Open AccessReview

Exploring Perinatal Asphyxia by Metabolomics

by Emanuela Locci, Giovanni Bazzano, Roberto Demontis, Alberto Chighine, Vassilios Fanos and Ernesto d’Aloja

Metabolites 2020, 10(4), 141; https://doi.org/10.3390/metabo10040141 - 04 Apr 2020

Cited by 28 | Viewed by 3236

Abstract

Brain damage related to perinatal asphyxia is the second cause of neuro-disability worldwide. Its incidence was estimated in 2010 as 8.5 cases per 1000 live births worldwide, with no further recent improvement even in more industrialized countries. If so, hypoxic-ischemic encephalopathy is still [...] Read more.

Brain damage related to perinatal asphyxia is the second cause of neuro-disability worldwide. Its incidence was estimated in 2010 as 8.5 cases per 1000 live births worldwide, with no further recent improvement even in more industrialized countries. If so, hypoxic-ischemic encephalopathy is still an issue of global health concern. It is thought that a consistent number of cases may be avoided, and its sequelae may be preventable by a prompt and efficient physical and therapeutic treatment. The lack of early, reliable, and specific biomarkers has up to now hampered a more effective use of hypothermia, which represents the only validated therapy for this condition. The urge to unravel the biological modifications underlying perinatal asphyxia and hypoxic-ischemic encephalopathy needs new diagnostic and therapeutic tools. Metabolomics for its own features is a powerful approach that may help for the identification of specific metabolic profiles related to the pathological mechanism and foreseeable outcome. The metabolomic profiles of animal and human infants exposed to perinatal asphyxia or developing hypoxic-ischemic encephalopathy have so far been investigated by means of ¹H nuclear magnetic resonance spectroscopy and mass spectrometry coupled with gas or liquid chromatography, leading to the identification of promising metabolomic signatures. In this work, an extensive review of the relevant literature was performed. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

16 pages, 686 KiB

Open AccessReview

The Determinants of the Human Milk Metabolome and Its Role in Infant Health

by Anna Ojo-Okunola, Stefano Cacciatore, Mark P. Nicol and Elloise du Toit

Metabolites 2020, 10(2), 77; https://doi.org/10.3390/metabo10020077 - 20 Feb 2020

Cited by 22 | Viewed by 4974

Abstract

Human milk is needed for optimal growth as it satisfies both the nutritional and biological needs of an infant. The established relationship between breastfeeding and an infant’s health is attributable to the nutritional and non-nutritional, functional components of human milk including metabolites such [...] Read more.

Human milk is needed for optimal growth as it satisfies both the nutritional and biological needs of an infant. The established relationship between breastfeeding and an infant’s health is attributable to the nutritional and non-nutritional, functional components of human milk including metabolites such as the lipids, amino acids, biogenic amines and carbohydrates. These components have diverse roles, including protecting the infant against infections and guiding the development of the infant’s immature immune system. In this review, we provide an in-depth and updated insight into the immune modulatory and anti-infective role of human milk metabolites and their effects on infant health and development. We also review the literature on potential determinants of the human milk metabolome, including maternal infectious diseases such as human immunodeficiency virus and mastitis. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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13 pages, 627 KiB

Open AccessReview

Intrauterine Growth Restriction: New Insight from the Metabolomic Approach

by Elena Priante, Giovanna Verlato, Giuseppe Giordano, Matteo Stocchero, Silvia Visentin, Veronica Mardegan and Eugenio Baraldi

Metabolites 2019, 9(11), 267; https://doi.org/10.3390/metabo9110267 - 06 Nov 2019

Cited by 37 | Viewed by 5296

Abstract

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn’s short- and long-term health. Ever since the first suggestion of the “thrifty phenotype hypothesis” in the last decade of the 20th century, a number [...] Read more.

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn’s short- and long-term health. Ever since the first suggestion of the “thrifty phenotype hypothesis” in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies’ trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics—a relatively new field of ‘-omics’ research—can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an “early” pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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Other

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7 pages, 504 KiB

Open AccessCase Report

A Case of Suspected Hyperphenylalaninemia at Newborn Screening by Tandem Mass Spectrometry during Total Parenteral Nutrition

by Damiana Pieragostino, Ilaria Cicalini, Silvia Di Michele, Paola Fusilli, Giovanna Cotugno, Rossella Ferrante, Ines Bucci, Carlo Dionisi-Vici, Liborio Stuppia, Vincenzo De Laurenzi and Claudia Rossi

Metabolites 2020, 10(2), 44; https://doi.org/10.3390/metabo10020044 - 24 Jan 2020

Cited by 9 | Viewed by 2961

Abstract

Phenylketonuria (PKU) is a rare autosomal recessive condition affecting about 1 in 10,000 people in the Europe, with a higher rate in some countries, like Ireland and Italy. In Italy, newborn screening (NBS) by MS/MS allows the diagnostic suspicion of PKU and its [...] Read more.

Phenylketonuria (PKU) is a rare autosomal recessive condition affecting about 1 in 10,000 people in the Europe, with a higher rate in some countries, like Ireland and Italy. In Italy, newborn screening (NBS) by MS/MS allows the diagnostic suspicion of PKU and its variants (Hyperphenylalaninemia (HPA), Tetrahydrobiopterin (BH4) synthesis deficiency, and Tetrahydrobiopterin (BH4) recycling deficiency) through the quantification of Phenylalanine (Phe) and the Phenylalanine/Tyrosine (Phe/Tyr) ratio in dried blood Spot (DBS) samples. Here, we report a case of an HPA whose suspicion was possible with expanded NBS, even if the normal-weight newborn was in total parenteral nutrition (TPN). It is known that TPN may present metabolic alterations, mainly for amino acids at NBS in MS/MS, frequently causing false positives. Actually, TPN is considered a special protocol in NBS, requiring several sample collections. In particular, a DBS sample is required before TPN, at basal time point (48 h after birth) and 72 h after the end of the procedure. In the case we report, even if the first DBS sample (before TPN) resulted negative, the repeated NBS tests revealed increased levels of Phe and dramatically high Phe/Tyr ratio. Thus, the newborn was recalled, and the NBS test was repeated several times before that HPA suspicion was confirmed by other specific biochemical tests. This case highlights the importance of Phe/Tyr ratio, only detectable by MS/MS analysis, in supporting the diagnostic suspicion during amino acids administration in the neonatal period. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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7 pages, 374 KiB

Open AccessCase Report

Serum Steroid Profiling by Liquid Chromatography–Tandem Mass Spectrometry for the Rapid Confirmation and Early Treatment of Congenital Adrenal Hyperplasia: A Neonatal Case Report

by Ilaria Cicalini, Stefano Tumini, Paola Irma Guidone, Damiana Pieragostino, Mirco Zucchelli, Sara Franchi, Gabriele Lisi, Pierluigi Lelli Chiesa, Liborio Stuppia, Vincenzo De Laurenzi and Claudia Rossi

Metabolites 2019, 9(12), 284; https://doi.org/10.3390/metabo9120284 - 21 Nov 2019

Cited by 8 | Viewed by 2748

Abstract

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in [...] Read more.

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in some cases, of mineralocorticoids. A variety of clinical presentations accompany a range of severities, which are described as different forms of CAH, and are the result of these hormonal imbalances. The incidence of CAH worldwide is approximately 1 in 15,000 live births, and is population-dependent; thus, its inclusion in neonatal screening tests is widely discussed. Diagnosis of CAH is based on the quantification of 17-hydroxyprogesterone, usually by immunoassay, which has low specificity and high false-positive rates, resulting in a relatively high demand for a second-tier confirmation test. We report a case of a newborn recognized as female at birth, but showing ambiguous genitalia and other CAH clinical features, including hypernatremia, in the first days of life. In addition to the classical assays, liquid chromatography–tandem mass spectrometry was used to determine the serum steroid profile, allowing for the accurate and simultaneous quantification of seven steroids in the same analysis. Such an application immediately revealed an alteration in the levels of specific steroids related to CAH, leading to an early intervention by hormone replacement therapy. Subsequently, the diagnosis of classic CAH due to 21-hydroxylase deficiency was further confirmed by molecular testing. Full article

(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)

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