Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

Azzopardi, Denis; Strohm, Brenda; Marlow, Neil; Brocklehurst, Peter; Deierl, Aniko; Eddama, Oya; Goodwin, Julia; Halliday, Henry L.; Juszczak, Edmund; Kapellou, Olga; Levene, Malcolm I.; Linsell, Louise; Omar, Omar; Thoresen, Marianne; Tusor, Nora; Whitelaw, Andrew; Edwards, A. David

doi:10.1056/nejmoa1315788

Cited by 608 publications

(504 citation statements)

References 16 publications

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“…Current evidences suggest that perinatal asphyxia can alter gene expression, inducing epigenetic changes in DNA methylation, histone modifications and modifying the rate of noncoding RNA synthesis (10); in addition, the response to asphyxia depends on genetic and epigenetic key factors, integrated each other (11,12). Therapeutic hypothermia (TH), a brain cooling technique, usually maintained over 72 hours after the hypoxic-ischemic event, has gained consensus for the treatment of perinatal asphyxia and HIE, reducing the mortality rate and long-term neurodevelopmental disabilities at 12-24 months of age (13,14). TH induces a slowdown in cerebral metabolism of approximately 5% every one degree fall in temperature, delaying the onset of anoxic cell depolarization (15).…”

Section: Introductionmentioning

confidence: 99%

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

Noto¹,

Pomero²,

Mussap³

et al. 2016

Ann. Transl. Med.

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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.

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Section: Introductionmentioning

confidence: 99%

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

Noto¹,

Pomero²,

Mussap³

et al. 2016

Ann. Transl. Med.

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“…Reifgeborenen und nahezu reifen Neugeborenen mit moderater bis schwerer hypoxisch-ischämischer Enzephalopathie soll, wenn möglich, eine therapeutische Hypothermie geboten werden [296][297][298][299][300][301] [106]. Auch wenn der AP-GAR-Score weiterhin im klinischen Alltag, für wissenschaftliche Studien und als prognostisches Hilfsmittel verwendet wird [302], wird seine Eignung durch die hohe inter-und intrapersonelle Variabilität bei seiner Erhebung zunehmend infrage gestellt.…”

Section: Therapeutische Hypothermieunclassified

Resuscitation and support of transition of babies at birth

Wyllie

Bruinenberg

Roehr

et al. 2015

Notfall Rettungsmed

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“…Születést követően az újszülöttek állapotfelmérése, a HIE diagnózisának gyors megállapí-tása lehetőséget ad a mérsékelt, teljes testre kiterjedő hypothermiás kezelés, mint az egyetlen bizonyítottan hatékony terápia mihamarabbi megkezdéséhez. Ennek célja a neuroprotekció [4].…”

unclassified

Terápiás hypothermia alkalmazása az asphyxiás újszülöttek kezelésében – egy hazai neonatológiai centrum eredményei

et al. 2017

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Bevezetés és célkitűzés:A hypothermiás kezelésben részesült hypoxiás-ischaemiás encephalopathiás újszülöttek össze-gyűjtött vizsgálati adatait elemeztük a Semmelweis Egyetem, I. Gyermekgyógyászati Klinika hármas szintű Perinatalis Intenzív Centrumában. Módszer: Retrospektív kohorszvizsgálatunkban a 2013-2015 között született, érett, hypoxiás-ischaemiás encephalopathia következtében hypothermiás kezelésben részesült 97 beteg adatait értékeltük, saját fejlesztésű regiszter segítségével. Eredmények: A gyermekek 59,8%-a császármetszéssel született, az első vérgázvizsgá-lat során észlelt pH 7,0 ± 0,2, pCO 2 55,9 ± 27,3 Hgmm, bázishiány 16,7 ± 7,2 mmol/l, illetve laktátszint 13,3 ± 4,7 mmol/l (x ± SD) volt. A hypothermiás kezelés 93,7%-ban már a neonatalis transzport alatt megkezdődött, átlagosan 2,5 ± 0,3 órás életkorban. Az asphyxiához gyakran társuló sokszervi elégtelenség betegeink 83,2%-ánál volt jelen. Az intenzív terápiával töltött medián idő 10,8 nap volt. Betegeink 61,3%-a az intenzív terápiát követően hazaadható volt, 32,2%-uk további klinikai kezelést igényelt, 6,5%-uk meghalt. Következtetés: A saját fejlesztésű regiszter segítségével az elmúlt évek kezelési eredményeinek gyors és könnyen kezelhető leíró elemzése vált lehetővé, ami megteremtette a belső audit és a prospektív betegkövetés feltételeit is. Orv. Hetil., 2017, 158(9), 331-339.Kulcsszavak: asphyxia neonatorum, hypoxiás-ischaemiás encephalopathia, hypothermia, perinatalis intenzív centrum Hypothermia treatment in asphyxiated neonates -a single center experience in Hungary Introduction and aim:We aimed to analyze patient characteristics of term neonates with hypoxic-ischemic encephalopathy treated with hypothermia at the 3rd level Neonatal Intensive Care Unit of the 1st Department of Pediatrics, Semmelweis University. Method: We conducted a retrospective cohort analysis between 2013-2015, including 97 asphyxiated neonates with HIE who received hypothermia treatment, using our in-house developed novel registry database. Results: 59.8% of neonates were born with Cesarean section and the first blood gas analysis showed a pH of 7.0 ± 0.2, pCO 2 55.9 ± 27.3 mmHg, base deficit 16.7 ± 7.2 mmol/l, and lactate levels of 13.3 ± 4.7 mmol/l (x ± SD). Hypothermia treatment was started during neonatal transport in 93.7% of the cases, at 2.5 ± 0.3 hours of age. Multiorgan failure associated with the perinatal asphyxia was present in 83.2% of the patients. Patients received intensive therapy for a median of 10.8 days, 61.3% of neonates were discharged home directly, 32.2% required further hospital treatment, and 6.5% died. Conclusion: Our novel registry database allowed for a quick, user-friendly and time-efficient analysis of patient characteristics in neonates with HIE. This registry could aid institutional audit work and prospective clinical data collection.

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Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

Abstract: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Cited by 608 publications

References 16 publications

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

Resuscitation and support of transition of babies at birth

Terápiás hypothermia alkalmazása az asphyxiás újszülöttek kezelésében – egy hazai neonatológiai centrum eredményei

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