Amino acid and acylcarnitine profiles in perinatal asphyxia: a case-control study

El-Farghali, Ola G.; El-Chimi, Mohamed Sami; Elabd, Heba Salah Abd-Elkhalek; Desouky, Eman D. El

doi:10.1080/14767058.2017.1319354

Cited by 13 publications

(17 citation statements)

References 23 publications

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“…Among these amino acids according to various studies, alanine, creatinine, isoleucine, leucine, methionine, phenylalaline, taurine, and valine are the most significant (cf. Table 2) (29,31,(54)(55)(56). The same finding has been observed in several animal studies (25,27,28,33).…”

Section: Blood Levelssupporting

confidence: 86%

“…Of note, only methionine levels showed the same trend systematically across the different studies and only alanine was found to be significantly higher in patients with severe HIE (grade 3) in comparison to asphyxiated patients without HIE and the control groups (29). Some amino acid levels were also significantly different amongst asphyxiated neonates who went on to develop HIE vs. those who did not (29,56). The levels of alanine, phenylalanine, valine and leucine were significantly higher in the HIE group studied by El-Farghali et al (56).…”

Section: Blood Levelsmentioning

confidence: 68%

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A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature

2021

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Perinatal asphyxia and the possible sequelae of hypoxic-ischemic encephalopathy (HIE), are associated with high morbidity and mortality rates. The use of therapeutic hypothermia (TH) commencing within the first 6 h of life—currently the only treatment validated for the management of HIE—has been proven to reduce the mortality rate and disability seen at follow up at 18 months. Although there have been attempts to identify neurobiomarkers assessing the severity levels in HIE; none have been validated in clinical use to date, and the lack thereof limits the optimal treatment for these vulnerable infants. Metabolomics is a promising field of the “omics technologies” that may: identify neurobiomarkers, help improve diagnosis, identify patients prone to developing HIE, and potentially improve targeted neuroprotection interventions. This review focuses on the current evidence of metabolomics, a novel tool which may prove to be a useful in the diagnosis, management and treatment options for this multifactorial complex disease. Some of the most promising metabolites analyzed are the group of acylcarnitines: Hydroxybutyrylcarnitine (Malonylcarnitine) [C3-DC (C4-OH)], Tetradecanoylcarnitine [C14], L-Palmitoylcarnitine [C16], Hexadecenoylcarnitine [C16:1], Stearoylcarnitine [C18], and Oleoylcarnitine [C18:1]. A metabolomic “fingerprint” or “index,” made up of 4 metabolites (succinate × glycerol/(β-hydroxybutyrate × O-phosphocholine)), seems promising in identifying neonates at risk of developing severe HIE.

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Section: Blood Levelssupporting

confidence: 86%

Section: Blood Levelsmentioning

confidence: 68%

A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature

2021

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“…Disruptions in oxidative metabolism and the switch to anaerobic metabolism associated with HIE lead to mitochondrial membrane depolarization, intracellular accumulation of Ca 2+ and extracellular build-up of excitatory amino acids 16–21 . The resulting metabolic acidosis is measurable, and others have reported alterations in amino acid and acyl-carnitine profiles similar to those described here 16,17,22–26 . Our finding that tyrosine was the screening analyte most strongly associated with HIE in our cohort has also been previously observed 25 .…”

Section: Discussionsupporting

confidence: 82%

Association between newborn screening analytes and hypoxic ischemic encephalopathy

Wilson

Fell

Hawken

et al. 2019

Sci Rep

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Hypoxic ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. Our study sought to examine whether patterns of newborn screening analytes differed between infants with and without neonatal HIE in order to identify opportunities for potential use of these analytes for diagnosis in routine clinical practice. We linked a population-based newborn screening registry with health databases to identify cases of HIE among term infants (≥37 weeks’ gestation) in Ontario from 2010–2015. Correlations between HIE and screening analytes were examined using multivariable logistic regression models containing clinical factors and individual screening analytes (acyl-carnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes). Among 731,841 term infants, 3,010 were diagnosed with HIE during the neonatal period. Multivariable models indicated that clinical variables alone or in combination with hemoglobin values were not associated with HIE diagnosis. Although the model was improved after adding acyl-carnitines and amino acids, the ability of the model to identify infants with HIE was moderate. Our findings indicate that analytes associated with catabolic stress were altered in infants with HIE; however, future research is required to determine whether amino acid and acyl-carnitine profiles could hold clinical utility in the early diagnosis or clinical management of HIE. In particular, further research should examine whether cord blood analyses can be used to identify HIE within a clinically useful timeframe or to guide treatment and predict long-term health outcomes.

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“…Lactate Plasma, urine, cord blood, CSF, brain tissue, ocular tissues [25,26,29,30,32,33,35,[38][39][40][41][42][45][46][47]49,51] Succinate Plasma, urine, cord blood, brain tissue [29,30,37,38,[40][41][42][43]45,47,49,50] Alanine Plasma, urine, cord blood, CSF, brain tissue [25,26,29,30,[37][38][39][40]48,49,52] Urine [36,38,45] BCAA, Branched Chain Amino Acids.…”

Section: Metabolite Sample Referencementioning

confidence: 99%

“…El-Farghali et al quantified the amino acids and acylcarnitines in cord blood dried spots collected from 45 full-term newborns exposed to PA (16 HIE and 29 non-HIE) and 20 matched healthy controls using UPLC-MS [52]. They detected differences in asphyctic samples with respect to controls but could also distinguish asphyxia from HIE.…”

Section: Human Studiesmentioning

confidence: 99%

Exploring Perinatal Asphyxia by Metabolomics

et al. 2020

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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 1 H 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.trigger several changes at molecular and cellular levels, which may end in cell death and in local/systemic inflammation. The shortage of oxygen, which acts as final electron acceptor in the electron transport chain (ETC) during aerobic respiration, induced by hypoxia and by ischemia, boosts reactive oxygen species (ROS) generation at the cellular level. Generated ROS attack surrounds components at both the mitochondrial and cellular level, leading to mitochondrial dysfunction and permanent damage to cells. The pathogenesis of HIE is strongly influenced by the failure of several potent fetal compensatory mechanisms to cope with the 'physiological' hypoxia during pregnancy and delivery. The final clinical outcome of such an insult is a wide spectrum of neurological deficits, ranging from behavioral and motor impairments to general developmental delays to seizures related to structural brain damage.The severity of the clinical picture of HIE infants is the final result of an uneven combination of several factors, and among them the length and strength of hypoxic insult, together with fetal metabolic conditions before the hypoxia onset. For this reason, the pathological effects are complex to forecast, and they evolve over time. They may be related to two main pathological phases: A primary and a secondary energy failure. Primary energy failure is the first biological effect of both hypoxia and a reduction of cerebral blood flow and it mainly takes place before birth. While the impairment of blood flow is responsible for the progressive reduction of glucose availability needed to fuel brain cells' metabo...

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Amino acid and acylcarnitine profiles in perinatal asphyxia: a case-control study

Abstract: We report UPLC-MS detectable alterations of amino acids and acylcarnitines in asphyxiated newborns at birth, that can serve as early diagnostic bedside biomarkers for HIE and predictors for its short-term outcome, and in the near future, as therapeutic targets.

Cited by 13 publications

References 23 publications

A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature

A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature

Association between newborn screening analytes and hypoxic ischemic encephalopathy

Exploring Perinatal Asphyxia by Metabolomics

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