Metabolomic and bioinformatic analyses in asphyxiated neonates (original) (raw)
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Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field
BioMed Research International, 2015
Metabolomics, the latest "omic" technology, is defined as the comprehensive study of all low molecular weight biochemicals, "metabolites" present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field.
Perinatal Asphyxia: A Review from a Metabolomics Perspective
Molecules (Basel, Switzerland), 2015
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last ye...
Exploring Perinatal Asphyxia by Metabolomics
Metabolites
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 ...
Metabolomics to Diagnose Oxidative Stress in Perinatal Asphyxia: Towards a Non-Invasive Approach
Antioxidants
There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is the study of small molecular weight products of cellular metabolism that may, directly and indirectly, reflect the level of oxidative stress. Saliva analysis is a novel approach that has a yet unexplored potential in metabolomics in perinatal asphyxia. The aim of this review was to give an overview of metabolomics studies of oxidative stress in perinatal asphyxia, particularly searching for studies analyzing non-invasively collected biofluids including saliva. We searched the databases PubMed/Medline and included 11 original human and 4 animal studies. In perinatal asphyxia, whole blood, plasma, and urine are the most frequently used biofluids used for metabolomics analyses. Although changes in oxidative stress-related salivary metabolites have been reported in adults, the utility of this approach in perinatal asphyxia has not yet been explored. Human and animal studies indicate that, in...
Annals of Translational Medicine, 2016
Background: Perinatal asphyxia is a severe clinical condition affecting around four million newborns worldwide. It consists of an impaired gas exchange leading to three biochemical components: hypoxemia, hypercapnia and metabolic acidosis. Methods: The aim of this longitudinal experimental study was to identify the urine metabolome of newborns with perinatal asphyxia and to follow changes in urine metabolic profile over time. Twelve babies with perinatal asphyxia were included in this study; three babies died on the eighth day of life. Total-body cooling for 72 hours was carried out in all the newborns. Urine samples were collected in each baby at birth, after 48 hours during hypothermia, after the end of the therapeutic treatment (72 hours), after 1 week of life, and finally after 1 month of life. Urine metabolome at birth was considered the reference against which to compare metabolic profiles in subsequent samples. Quantitative metabolic profiling in urine samples was measured by gas chromatography mass spectrometry (GC-MS). The statistical approach was conducted by using the multivariate analysis by means of principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Pathway analysis was also performed. Results: The most important metabolites depicting each time collection point were identified and compared each other. At birth before starting therapeutic hypothermia (TH), urine metabolic profiles of the three babies died after 7 days of life were closely comparable each other and significantly different from those in survivors. Conclusions: In conclusion, a plethora of data have been extracted by comparing the urine metabolome at birth with those observed at each time point collection. The modifications over time in metabolites composition and concentration, mainly originated from the depletion of cellular energy and homeostasis, seems to constitute a fingerprint of perinatal asphyxia.
Understanding neonatal hypoxic-ischemic encephalopathy with metabolomics
Hippokratia, 2017
BACKGROUND Hypoxic-ischemic encephalopathy (HIE), a serious complication of perinatal asphyxia, is commonly associated with an unfavorable outcome. In-depth research is important not only for the interpretation of the underlying biological alternations but may also provide the basis for the development of novel diagnostic and therapeutic tools. The application of metabolomics in perinatal asphyxia/HIE is a relatively new approach. METHODS We performed a narrative, non-systematic review in the literature of metabolomic studies involving newborn animals and humans exposed to hypoxia-ischemia or developing perinatal asphyxia/HIE. RESULTS Fifteen animal studies, nine studies in human neonates, and two review articles were evaluated. Changes in the metabolomic profile of newborn animals exposed to hypoxia-ischemia and of asphyxiated neonates with HIE are presented in relation to the underlying pathophysiology. The clinical relevance of these findings is further discussed in a comprehe...
Urine metabolomic profiling in neonatal nephrology
Clinical Biochemistry, 2014
a b s t r a c t 7 after asphyxia. This is responsible of the different behaviors of piglets 66 after a strong hypoxic stimulus giving rise to asystolia and/or shock. 67 After resuscitation, performed following a rigorous protocol by (the 68 same anesthesiologist in the same way with the same drugs) some 69 piglets die, others reach pre-hypoxic conditions after several hours 70 and they suffer from multi-organ failure (MOF), including acute kid-71 ney injury; finally other piglets reach basal pre-hypoxic values after 1 V. Fanos et al. / Clinical Biochemistry xxx (2014) Please cite this article as: Fanos V, et al, Urine metabolomic profiling in neonatal nephrology, Clin Biochem (2014), http://dx.doi.org/10.1016/ j.clinbiochem.2014.05.020 resuscitation very early (within 15 min). This is an expression of an in-73 trinsic resilience of the subject. Interestingly and surprisingly urinary 74 metabolomics performed on samples before resuscitation are able to 75 predict and anticipate the destiny of the piglet (death, MOF, quick 76 recovery). Piglets die Q7 by 2 different mechanisms (either cardiac or 77 respiratory): while today we are treating all of them in the same way 78
Urine metabolomic profile in neonates with hypoxic-ischemic encephalopa-thy
2017
BACKGROUND Metabolomics could provide valuable insights into hypoxemic-ischemic encephalopathy (HIE) revealing new disease-associated biochemical derangements. The study aimed to investigate urine metabolic changes in neonates with HIE compared to healthy controls, using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). PATIENTS AND METHODS In this prospective, single-center study we enrolled neonates born at ≥ 36 weeks gestation with HIE (HIE group) and healthy controls (control group). We collected urine samples for metabolomic analysis on days one, three, and nine of life. RESULTS Twenty-one full-term newborns were studied, 13 in the HIE group and eight in the control group. Six of the affected neonates had moderate/severe HIE and seven mild HIE. Therapeutic hypothermia was applied only in four neonates with moderate/severe HIE. Multivariate and univariate statistical analysis showed a clear separation between the HIE and the control groups. Discriminant metabol...
Early Human Development, 2013
s u m m a r y Metabolomics (or metabonomics) is based on the systematic study of the complete set of metabolites in a biological sample and is considered the most innovative of the 'omics' sciences. The metabolome is currently regarded as the 'new clinical biochemistry'; it is the most predictive phenotype, through consideration of epigenetic differences. Among more than 5000 papers listed in PubMed on this topic in the last three years, less than 60 refer to neonatal life. Aim of this review is to present the clinical applications of metabolomics in neonatology, including results of recent studies performed in experimental models and newborns.
Metabolomics - Fundamentals and Applications, 2016
Throughout recent decades, the incidence of preterm birth has risen worldwide, and although the majority of preterm neonates now survive infancy, many suffer from debilitating morbidities in the short term and/or increased disease risks in the long term. Traditional diagnostic biomarkers suffer from considerable confounders, limiting their use in the early identification of diseases. There is a need to develop novel biomarkers that can identify, in real time, the evolution of organ dysfunction in an early diagnostic, monitoring, and prognostic fashion. Use of "omics," particularly metabolomics, may provide valuable information regarding functional pathways underlying different pathologies and prediction of clinical outcomes. The emerging knowledge generated by the application of metabolomics in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, response to treatment, and new therapeutic targets. In this chapter, we review the current knowledge of different metabolomics technologies in neonatal-perinatal medicine, including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of metabolomics to relevant standard indices and long-term outcomes.