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1.
Neurotox Res ; 36(3): 472-490, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31187430

RESUMO

We have recently reported that global perinatal asphyxia (PA) induces a regionally sustained increase in oxidized glutathione (GSSG) levels and GSSG/GSH ratio, a decrease in tissue-reducing capacity, a decrease in catalase activity, and an increase in apoptotic caspase-3-dependent cell death in rat neonatal brain up to 14 postnatal days, indicating a long-term impairment in redox homeostasis. In the present study, we evaluated whether the increase in GSSG/GSH ratio observed in hippocampus involves changes in glutathione reductase (GR) and glutathione peroxidase (GPx) activity, the enzymes reducing glutathione disulfide (GSSG) and hydroperoxides, respectively, as well as catalase, the enzyme protecting against peroxidation. The study also evaluated whether there is a shift in the metabolism towards the penthose phosphate pathway (PPP), by measuring TIGAR, the TP53-inducible glycolysis and apoptosis regulator, associated with delayed cell death, further monitoring calpain activity, involved in bax-dependent cell death, and XRCC1, a scaffolding protein interacting with genome sentinel proteins. Global PA was induced by immersing fetus-containing uterine horns removed by a cesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling cesarean-delivered fetuses were manually resuscitated and nurtured by surrogate dams. Animals were euthanized at postnatal (P) days 1 or 14, dissecting samples from hippocampus to be assayed for glutathione, GR, GPx (all by spectrophotometry), catalase (Western blots and ELISA), TIGAR (Western blots), calpain (fluorescence), and XRCC1 (Western blots). One hour after delivery, asphyxia-exposed and control neonates were injected with either 100 µl saline or 0.8 mmol/kg nicotinamide, i.p., shown to protect from the short- and long-term consequences of PA. It was found that global PA produced (i) a sustained increase of GSSG levels and GSSG/GSH ratio at P1 and P14; (ii) a decrease of GR, GPx, and catalase activity at P1 and P14; (iii) a decrease at P1, followed by an increase at P14 of TIGAR levels; (iv) an increase of calpain activity at P14; and (v) an increase of XRCC1 levels, but only at P1. (vi) Nicotinamide prevented the effect of PA on GSSG levels and GSSG/GSH ratio, and on GR, GPx, and catalase activity, also on increased TIGAR levels and calpain activity observed at P14. The present study demonstrates that the long-term impaired redox homeostasis observed in the hippocampus of rats subjected to global PA implies changes in GR, GPx, and catalase, and a shift towards PPP, as indicated by an increase of TIGAR levels at P14.


Assuntos
Asfixia Neonatal/complicações , Glutationa/metabolismo , Hipocampo/metabolismo , Niacinamida/farmacologia , Estresse Oxidativo , Via de Pentose Fosfato , Animais , Asfixia Neonatal/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Homeostase/efeitos dos fármacos , Redes e Vias Metabólicas , Estresse Oxidativo/efeitos dos fármacos , Via de Pentose Fosfato/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/metabolismo , Ratos , Ratos Wistar
2.
Clin Perinatol ; 46(2): 273-290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010560

RESUMO

There is a distinct lack of age-appropriate cardiotonic drugs, and adult derived formulations continue to be administered, without evidence-based knowledge on their dosing, safety, efficacy, and long-term effects. Dopamine remains the most commonly studied and prescribed cardiotonic drug in the neonatal intensive care unit (NICU), but evidence of its effect on endorgan perfusion still remains. Unlike adult and pediatric critical care, there are significant gaps in our knowledge on the use of various cardiotonic drugs in various forms of circulatory failure in the NICU.


Assuntos
Cardiotônicos/uso terapêutico , Hipotensão/tratamento farmacológico , Choque/tratamento farmacológico , Vasoconstritores/uso terapêutico , Corticosteroides/uso terapêutico , Asfixia Neonatal/complicações , Dobutamina/uso terapêutico , Dopamina/uso terapêutico , Cardiopatias Congênitas/complicações , Humanos , Hipotensão/etiologia , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Milrinona/uso terapêutico , Sepse Neonatal/complicações , Norepinefrina/uso terapêutico , Síndrome da Persistência do Padrão de Circulação Fetal/complicações , Choque/etiologia , Simendana/uso terapêutico , Vasopressinas/uso terapêutico
3.
J Neonatal Perinatal Med ; 12(2): 127-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30741696

RESUMO

BACKGROUND: Perinatal asphyxia is a prominent cause of neonatal mortality in the developing world. Growth in head circumference is associated with improved neurodevelopment. Previous studies found a positive correlation between additional dietary supplementation and growth in head circumference among newborns with perinatal brain injury. This study aims to evaluate the association between anthropometric parameters and developmental outcomes in newborns with hypoxic ischemic encephalopathy (HIE). METHODS: Newborns at ≥36 weeks gestation with moderate to severe HIE were included in the study and growth parameters were monitored. Newborns with life-threatening anomalies were excluded. None of the study participants received therapeutic hypothermia (TH). Developmental Assessment Scale for Indian Infants (DASII) was used to evaluate neurodevelopmental outcomes at 1 year of age. RESULTS: Of 76 study participants, 46 were followed for 12 months, 28 died, and 2 were lost to follow-up. HIE stage III, Apgar score <5 at 5 minutes of age, pH ≤ 7.1 on first blood gas and base deficit > - 16 was associated with death or disability at 1 year of age. All anthropometric parameters were significantly lower in presence of death or disability. pH ≤ 7.1 at birth (odds ratio: 11.835, 95% CI 2.273-61.629, p = 0.003) and weight gain at one year (odds ratio 1.001, 95% CI 1.000-1.002, p = 0.03) were significantly associated with death and disability. CONCLUSION: pH > 7.1 at birth, and weight gain were associated with better neurodevelopmental outcomes at 1 year of age. Thus, in addition to TH, nutritional interventions may potentially improve outcomes among newborns with HIE.


Assuntos
Asfixia Neonatal/fisiopatologia , Peso Corporal , Cefalometria , Desenvolvimento Infantil , Cabeça/crescimento & desenvolvimento , Hipóxia-Isquemia Encefálica/fisiopatologia , Ganho de Peso , Antropometria , Anticonvulsivantes/uso terapêutico , Asfixia Neonatal/complicações , Gasometria , Paralisia Cerebral/epidemiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipóxia-Isquemia Encefálica/complicações , Índia , Lactente , Recém-Nascido , Masculino , Microcefalia/epidemiologia , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Índice de Gravidade de Doença
4.
J Matern Fetal Neonatal Med ; 32(16): 2727-2734, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29504433

RESUMO

OBJECTIVE: To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country. STUDY DESIGN: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings. RESULTS: Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p < .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p < .001; p = .001; p = .001, and p = .011, respectively). CONCLUSIONS: Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.


Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imagem por Ressonância Magnética/métodos , Adulto , Asfixia Neonatal/complicações , Brasil/epidemiologia , Estudos de Casos e Controles , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipotermia Induzida/mortalidade , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
5.
J Matern Fetal Neonatal Med ; 32(14): 2302-2309, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29357720

RESUMO

AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution volume (Vd) and elimination half-life (t1/2) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (TnormaEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7.1 + Apgar score ≤5 (5 min), dichotomous]. Student's t-test, two-way ANOVA, correlation and Pearson's chi-square test were used. RESULTS: Forty newborns were included [14 non-HT; 26 HT with TnormaEEG <24 h in 14/26 (group1-HT) and TnormaEEG ≥24 h in 12/26 (group2-HT)]. Severe asphyxia was present in 26/40 [5/14 non-HT, 11/14 and 10/12 in both HT groups]. PB-CL, Vd and t1/2 were similar between the non-HT and HT group. However, within the HT group, PB-CL was significantly different between group1-HT and group2-HT (p = .043). ANOVA showed that HT (p = .034) and severity of asphyxia (p = .038) reduced PB-CL (-50%). CONCLUSION: The interaction of severity of asphyxia and HT is associated with a clinical relevant reduced PB-CL, suggesting the potential relevance of disease characteristics beyond HT itself.


Assuntos
Anticonvulsivantes/farmacocinética , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Fenobarbital/farmacocinética , Índice de Gravidade de Doença , Análise de Variância , Anticonvulsivantes/administração & dosagem , Índice de Apgar , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Estudos de Casos e Controles , Feminino , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Recém-Nascido , Masculino , Taxa de Depuração Metabólica , Fenobarbital/administração & dosagem , Estudos Prospectivos
6.
Arch Dis Child Fetal Neonatal Ed ; 104(3): F285-F292, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29997167

RESUMO

OBJECTIVE: To assess the impact of hypothermic neural rescue for perinatal asphyxia at birth on healthcare costs of survivors aged 6-7 years, and to quantify the relationship between costs and overall disability levels. DESIGN: 6-7 years follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial. SETTING: Community study including a single parental questionnaire to collect information on children's healthcare resource use. PATIENTS: 130 UK children (63 in the control group, 67 in the hypothermia group) whose parents consented and returned the questionnaire. INTERVENTIONS: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone. MAIN OUTCOME MEASURES: Healthcare resource usage and costs over the preceding 6 months. RESULTS: At 6-7 years, mean (SE) healthcare costs per child were £1543 (£361) in the hypothermia group and £2549 (£812) in the control group, giving a saving of -£1005 (95% CI -£2734 to £724). Greater levels of overall disability were associated with progressively higher costs, and more parents in the hypothermia group were employed (64% vs 47%). Results were sensitive to outlying observations. CONCLUSIONS: Cost results although not significant favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. Estimates were however sensitive to the care requirements of two seriously ill children in the control group. A quantification of the relationship between costs and levels of disability experienced will be useful to healthcare professionals, policy makers and health economists contemplating the long-term economic consequences of perinatal asphyxia and hypothermic neural rescue. TRIAL REGISTRATION NUMBER: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials. gov number NCT01092637.


Assuntos
Asfixia Neonatal/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/estatística & dados numéricos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Asfixia Neonatal/complicações , Deficiências do Desenvolvimento/economia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Crianças com Deficiência/estatística & dados numéricos , Feminino , Seguimentos , Recursos em Saúde/economia , Humanos , Hipóxia-Isquemia Encefálica/complicações , Recém-Nascido , Inteligência , Masculino , Psicometria
7.
Pediatr Nephrol ; 34(1): 169-176, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30155763

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in neonatal encephalopathy (NE) and is associated with worse outcomes. Our objectives were to determine the incidence, risk factors, and outcomes of AKI in infants with NE. METHODS: We performed a retrospective analysis of infants ≥ 34 weeks' gestational age with a diagnosis of NE from the Analysis of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) database. AKI was defined using the modified Kidney Disease Improving Global Outcomes criteria. Perinatal and postnatal factors were evaluated. Multivariate logistic and linear regressions were performed. RESULTS: One hundred and thirteen patients with NE were included. 41.6% (47) developed AKI. Being born outside the admitting institution (OR 4.3; 95% CI 1.2-14.8; p = 0.02), intrauterine growth restriction (OR 10.3, 95% CI 1.1-100.5; p = 0.04), and meconium at delivery (OR 2.8, 95% CI 1.04-7.7; p = 0.04) conferred increased odds of AKI. After controlling for confounders, infants with AKI stayed in the hospital an average of 8.5 days longer than infants without AKI (95% CI 0.79-16.2 days; p = 0.03). CONCLUSIONS: In this multi-national analysis, several important perinatal factors were associated with AKI and infants with both NE and AKI had longer length of stay than NE alone. Future research aimed at early AKI detection, renoprotective management strategies, and understanding the long-term renal consequences is warranted in this high-risk group of patients.


Assuntos
Lesão Renal Aguda/epidemiologia , Asfixia Neonatal/complicações , Encefalopatias/etiologia , Retardo do Crescimento Fetal/epidemiologia , Lesão Renal Aguda/etiologia , Bases de Dados Factuais/estatística & dados numéricos , Conjuntos de Dados como Assunto , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação/estatística & dados numéricos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco
8.
Eur J Paediatr Neurol ; 23(1): 181-190, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30279083

RESUMO

OBJECTIVE: The aim was to establish any differences in the predictive value of EEG and MRI for outcome in infants treated and not-treated with therapeutic hypothermia (HT) for perinatal asphyxia. We hypothesize that they are equally predictive and that combining both has the highest predictive value. STUDY DESIGN: We retrospectively compared data of infants with hypoxic-ischemic encephalopathy (HIE) who received HT (n = 45) between September 2009 and December 2013 with those of infants with HIE born between January 2004 and August 2009, before HT was available (NT, n = 37). All received conventional and/or amplitude-integrated EEG during the first days and early MRI (day 4-5). Associations of EEG, MRI and severe neurodevelopmental outcome (death or Bayley's -2SD below mean), were tested with a multivariable logistic regression analysis, corrected for HT. RESULTS: Forty-eight hours' EEG background pattern had a PPV of 92% and a NPV of 81% in HT, versus 100% and 58% in NT. MRI had a PPV of 71% and a NPV of 93% in HT, versus 82% and 75% in NT. The adjusted OR for adverse outcome was 0.013 (95% CI 0.002-0.154, p < 0.001) for EEG background normalization within 48 h and 32.19 (95% CI 4.84-214.25, p < 0.001) for abnormal MRI. CONCLUSION: The predictive value of EEG and MRI is equal in cooled and non-cooled infants with HIE. Our data show a higher predictive value (death and severe outcome) for EEG compared to MRI. In HIE, persistent abnormal EEG background pattern until 48 h, combined with abnormal early MRI is strongly predictive for poor neurodevelopment.


Assuntos
Asfixia Neonatal/patologia , Eletroencefalografia/métodos , Hipóxia-Isquemia Encefálica/patologia , Imagem por Ressonância Magnética/métodos , Asfixia , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Encéfalo/patologia , Encéfalo/fisiopatologia , Feminino , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos
9.
J Matern Fetal Neonatal Med ; 32(8): 1312-1320, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29129133

RESUMO

PURPOSE: Therapeutic hypothermia is the standard treatment for asphyxiated newborns. Since hypocapnia is common in these newborns, the aim of this study was to assess the association among hypocapnia, ventilation, and brain injury. METHODS: We conducted a retrospective cohort study of all asphyxiated newborns treated with hypothermia from 2008 to 2014. Partial pressure of carbon dioxide (pCO2), ventilatory status, and modes of ventilation were recorded during the first 4 days of life. Brain injury was evaluated using brain magnetic resonance imaging. Differences between intubated and nonintubated newborns and between the newborns who developed brain injury or not were assessed. RESULTS: One hundred ninety-eight asphyxiated newborns were treated with hypothermia. During the first 2 days of life, intubated newborns had consistently lower pCO2 levels (respectively, 29.01 ± 8.55, p < .001 on day 1 of life and 33.65 ± 7.12, p = .004 on day 2 of life). Fifty-nine percent of the intubated newborns developed brain injury versus only 43% of the nonintubated newborns (p = .046). The lowest pCO2 levels averaged over the first 4 days of life were significantly decreased in newborns developing brain injury (p = .02) and significantly associated with brain injury severity (p = .01). After adjusting for potential cofounders, the lowest pCO2 averaged over days 1-4 of life remained significantly associated with an increased risk of brain injury (odds ratio [95%CI]: 1.07 [1.00-1.14]; p = .04). CONCLUSIONS: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.


Assuntos
Asfixia Neonatal/terapia , Hipocapnia/complicações , Hipotermia Induzida/efeitos adversos , Hipóxia-Isquemia Encefálica/etiologia , Respiração Artificial/efeitos adversos , Asfixia Neonatal/complicações , Feminino , Idade Gestacional , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Masculino , Respiração Artificial/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
J Am Heart Assoc ; 7(19): e009728, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30371318

RESUMO

Background The American Heart Association recommends use of physiologic feedback when available to optimize chest compression delivery. We compared hemodynamic parameters during cardiopulmonary resuscitation in which either end-tidal carbon dioxide ( ETCO 2) or diastolic blood pressure ( DBP ) levels were used to guide chest compression delivery after asphyxial cardiac arrest. Methods and Results One- to 2-week-old swine underwent a 17-minute asphyxial-fibrillatory cardiac arrest followed by alternating 2-minute periods of ETCO 2-guided and DBP -guided chest compressions during 10 minutes of basic life support and 10 minutes of advanced life support. Ten animals underwent resuscitation. We found significant changes to ETCO 2 and DBP levels within 30 s of switching chest compression delivery methods. The overall mean ETCO 2 level was greater during ETCO 2-guided cardiopulmonary resuscitation (26.4±5.6 versus 22.5±5.2 mm Hg; P=0.003), whereas the overall mean DBP was greater during DBP -guided cardiopulmonary resuscitation (13.9±2.3 versus 9.4±2.6 mm Hg; P=0.003). ETCO 2-guided chest compressions resulted in a faster compression rate (149±3 versus 120±5 compressions/min; P=0.0001) and a higher intracranial pressure (21.7±2.3 versus 16.0±1.1 mm Hg; P=0.002). DBP -guided chest compressions were associated with a higher myocardial perfusion pressure (6.0±2.8 versus 2.4±3.2; P=0.02) and cerebral perfusion pressure (9.0±3.0 versus 5.5±4.3; P=0.047). Conclusions Using the ETCO 2 or DBP level to optimize chest compression delivery results in physiologic changes that are method-specific and occur within 30 s. Additional studies are needed to develop protocols for the use of these potentially conflicting physiologic targets to improve outcomes of prolonged cardiopulmonary resuscitation.


Assuntos
Asfixia Neonatal/complicações , Pressão Sanguínea/fisiologia , Dióxido de Carbono/metabolismo , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Massagem Cardíaca/métodos , Monitorização Fisiológica/métodos , Animais , Animais Recém-Nascidos , Asfixia Neonatal/fisiopatologia , Diástole , Modelos Animais de Doenças , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Masculino , Projetos Piloto , Suínos
11.
Medicina (B Aires) ; 78 Suppl 2: 36-41, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30199363

RESUMO

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).


Assuntos
Hipóxia-Isquemia Encefálica/diagnóstico , Asfixia Neonatal/complicações , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Incidência , Recém-Nascido , Índice de Gravidade de Doença
12.
J Perinatol ; 38(11): 1512-1517, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206346

RESUMO

OBJECTIVE: To evaluate whether a strategy of restricted fluid intake in the first 4 days reduces mortality and morbidity among term neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. STUDY DESIGN: Eighty neonates with HIE were randomized between January 2016 and February 2018 to receive normal fluid intake (n = 40) or restricted fluid intake (two-third of normal intake; n = 40) in the first 4 days of life. The primary outcome was a composite of death or major neurodevelopmental disability at 6 months of age. RESULTS: The primary outcome occurred in 10 infants (26%) in the fluid-restricted group and 3 infants (8%) in the normal fluid intake group, but the difference was not statistically significant (p = 0.065). Five infants in the fluid-restricted group had hypoglycemia (p = 0.055). CONCLUSION: Restricted fluid intake did not reduce the composite outcome of death or neurodevelopmental disability and was associated with a trend toward more hypoglycemia.


Assuntos
Asfixia Neonatal/complicações , Hidratação , Hipóxia-Isquemia Encefálica/terapia , Edema Encefálico/prevenção & controle , Feminino , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/etiologia , Índia , Recém-Nascido , Masculino , Projetos Piloto
13.
Lakartidningen ; 1152018 08 23.
Artigo em Sueco | MEDLINE | ID: mdl-30152852

RESUMO

Hypothermic treatment after birth asphyxia was introduced as a recommended practice in Sweden in 2007. CPUP is a national quality register and surveillance program that encompasses the total population of children with cerebral palsy (CP) in Sweden. In an analysis of CPUP data children with CP and asphyxia treated with cooling were compared to children with CP and asphyxia who were not cooled. A lower proportion of severe motor and cognitive impairments were observed in the group that did receive the cooling/hypothermic treatment.


Assuntos
Asfixia Neonatal , Paralisia Cerebral , Hipotermia Induzida , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Paralisia Cerebral/classificação , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Disfunção Cognitiva/classificação , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Humanos , Recém-Nascido , Destreza Motora/classificação , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Suécia/epidemiologia , Resultado do Tratamento
15.
Early Hum Dev ; 125: 1-7, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30144709

RESUMO

BACKGROUND: Therapeutic hypothermia reduces the risk of death, or moderate to severe neurodevelopmental impairment (NDI) in term infants with hypoxic-ischemic encephalopathy (HIE). Reports of its safety and efficacy in preterm infants are scarce. OBJECTIVE: Report short and long-term outcomes of preterm infants with HIE who received therapeutic hypothermia. METHODS: A retrospective cohort analysis of all preterm infants <36 weeks' gestation with HIE who received whole body hypothermia in a single center from January 2007 to April 2015. The primary outcome was death or moderate to severe NDI defined by moderate or severe cerebral palsy, severe hearing or visual impairment, or cognitive score < 85 on the Bayley Scales of Infant Development III (BSID III) at 18-24 months' adjusted age. RESULTS: 30 infants with a median gestational age and birthweight of 35 weeks' (range; 33-35) and 2575 g (1850-4840) and a median first postnatal blood pH of 6.81 (6.58-7.14). Complications included coagulopathy (50%), early clinical seizures (43.3%), arterial hypotension (40%), persistent metabolic acidosis (37%) and thrombocytopenia (20%). Four infants died before or soon after discharge (18.2%). Eighteen surviving infants (69.2%) had follow up data; 7 of them had moderate to severe NDI (38.9%). Cognitive, motor and language mean composite BSID III scores were 84 (54-110), 83 (46-118), and 78 (46-112). Death or moderate to severe NDI occurred in 11/22 (50%) infants with known outcomes. CONCLUSION: Large randomized trials on efficacy and safety are needed in this highly vulnerable population as the incidence of complications and the combined outcome of death and NDI is concerning.


Assuntos
Asfixia Neonatal/terapia , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Asfixia Neonatal/complicações , Peso ao Nascer/fisiologia , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Retrospectivos , Resultado do Tratamento
16.
Childs Nerv Syst ; 34(12): 2463-2469, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30022316

RESUMO

BACKGROUND: Therapeutic hypothermia is a method of treatment in newborns with hypoxic ischemic encephalopathy. Hypothermia should be initiated no later than 6 h after birth. The purpose of this study was to evaluate the quality of the passive therapeutic cooling during neonatal transport. PURPOSE: The study aims to evaluate the efficiency of our transport in maintenance of target body temperature during transport. METHODS: We conducted a 10-year retrospective study in neonates, transported by helicopter or ambulance, who received therapeutic passive-induced hypothermia during transport to the Department of Pediatric Surgery and Intensive Therapy at the University Medical Centre Ljubljana between September 1, 2006, and December 31, 2016. RESULTS: Out of 68 transported newborns, 57 met the criteria for therapeutic induced hypothermia. Eight out of 51 (15.7%) were within therapeutic temperature zone before start of transport while 30 out of 57 (52.6%) were within therapeutic temperature zone at the end of transport. There was a negative correlation between the duration of transport and temperature at the admission (ρ = - 0.306; p = 0.026). A positive correlation was found between the body temperature before and at the end of transport (ρ = 0.410; p = 0,003). A positive correlation between axillary and rectal temperature on admission was found (ρ = 0,832; p < 0,0005). The type of transport, meteorological season, or gender differences did not affect any of measured parameters. Newborns who received chest compression had lower temperature. CONCLUSION: Therapeutic temperature zone during transport was achieved in 52.6% of transported neonates. Axillary temperature positively correlated with rectal temperature on admission.


Assuntos
Asfixia Neonatal/terapia , Serviços Médicos de Emergência/métodos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Resgate Aéreo , Ambulâncias , Asfixia Neonatal/complicações , Feminino , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Recém-Nascido , Masculino , Estudos Retrospectivos
17.
Am J Physiol Heart Circ Physiol ; 315(4): H978-H988, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30028198

RESUMO

Neonatal asphyxia leads to cerebrovascular disease and neurological complications via a mechanism that may involve oxidative stress. Carbon monoxide (CO) is an antioxidant messenger produced via a heme oxygenase (HO)-catalyzed reaction. Cortical astrocytes are the major cells in the brain that express constitutive HO-2 isoform. We tested the hypothesis that CO, produced by astrocytes, has cerebroprotective properties during neonatal asphyxia. We developed a survival model of prolonged asphyxia in newborn pigs that combines insults of severe hypoxia, hypercapnia, and acidosis while avoiding extreme hypotension and cerebral blood flow reduction. During the 60-min asphyxia, CO production by brain and astrocytes was continuously elevated. Excessive formation of reactive oxygen species during asphyxia/reventilation was potentiated by the HO inhibitor tin protoporphyrin, suggesting that endogenous CO has antioxidant effects. Cerebral vascular outcomes tested 24 and 48 h after asphyxia demonstrated the sustained impairment of cerebral vascular responses to astrocyte- and endothelium-specific vasodilators. Postasphyxia cerebral vascular dysfunction was aggravated in newborn pigs pretreated with tin protoporphyrin to inhibit brain HO/CO. The CO donor CO-releasing molecule-A1 (CORM-A1) reduced brain oxidative stress during asphyxia/reventilation and prevented postasphyxia cerebrovascular dysfunction. The antioxidant and antiapoptotic effects of HO/CO and CORM-A1 were confirmed in primary cultures of astrocytes from the neonatal pig brain exposed to glutamate excitotoxicity. Overall, prolonged neonatal asphyxia leads to neurovascular injury via an oxidative stress-mediated mechanism that is counteracted by an astrocyte-based constitutive antioxidant HO/CO system. We propose that gaseous CO or CO donors can be used as novel approaches for prevention of neonatal brain injury caused by prolonged asphyxia. NEW & NOTEWORTHY Asphyxia in newborn infants may lead to lifelong neurological disabilities. Using the model of prolonged asphyxia in newborn piglets, we propose novel antioxidant therapy based on systemic administration of low doses of a carbon monoxide donor that prevent loss of cerebral blood flow regulation and may improve the neurological outcome of asphyxia.


Assuntos
Arteríolas/efeitos dos fármacos , Asfixia Neonatal/tratamento farmacológico , Astrócitos/efeitos dos fármacos , Boranos/farmacologia , Dióxido de Carbono/metabolismo , Carbonatos/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Pia-Máter/irrigação sanguínea , Animais , Animais Recém-Nascidos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Arteríolas/metabolismo , Arteríolas/fisiopatologia , Asfixia Neonatal/complicações , Asfixia Neonatal/metabolismo , Asfixia Neonatal/fisiopatologia , Astrócitos/metabolismo , Astrócitos/patologia , Velocidade do Fluxo Sanguíneo , Células Cultivadas , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/fisiopatologia , Modelos Animais de Doenças , Feminino , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sus scrofa , Fatores de Tempo , Vasodilatação/efeitos dos fármacos
18.
Resuscitation ; 130: 99-104, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30009925

RESUMO

AIM: To assess the electrocardiography and echocardiography changes during therapeutic hypothermia and rewarming period in encephalopathic infants with long-term adverse neurological outcome. METHODS: Prospective multicentre longitudinal study. We included 64 consecutive infants with moderate or severe hypoxic ischaemic encephalopathy undergoing therapeutic hypothermia who had 18-24 month-outcome data. We analysed electrocardiography and heart rate changes before, during and after therapeutic hypothermia. Superior vena cava flow, left ventricular cardiac output and stroke volume were studied using echocardiography during and immediately after therapeutic hypothermia. An abnormal outcome was defined as death or moderate/severe disability at 18-24 months. RESULTS: Neonates with higher superior vena cava flow pre-rewarming had significantly higher odds of documented long-term adverse outcome when compared to newborns with good outcome (OR 1.57; 95%CI, 1.1-1.78; p = 0.01 after adjustment). QTc and RR intervals were significantly longer at 12, 24, 36 and 48 h in infants with good outcome compared with those with adverse outcome (p < 0.001). During therapeutic hypothermia, infants with poor outcome had a higher heart rate at 12, 24, 36, 48, 60 h after birth compared with those with good outcome (p < 0.001). From 36 h on, heart rate gradually increased and RR and QTc intervals progressively shortened with values back to normal after rewarming. CONCLUSIONS: Infants with hypoxic ischaemic encephalopathy who have adverse neurological outcome show a preferential cerebral blood flow redistribution during therapeutic hypothermia. Infants with poor outcome have higher heart rate and shorter RR and QTc intervals during therapeutic hypothermia.


Assuntos
Asfixia Neonatal/complicações , Débito Cardíaco , Circulação Cerebrovascular , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Reaquecimento/métodos , Volume Sistólico , Ecocardiografia/métodos , Eletrocardiografia/métodos , Feminino , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Efeitos Adversos de Longa Duração/diagnóstico , Estudos Longitudinais , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Veia Cava Superior/fisiopatologia
19.
J Child Neurol ; 33(12): 767-771, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30032694

RESUMO

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) ( P value < .05). Mean serum homocysteine level (13.9 vs 7.8 µmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls ( P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms.


Assuntos
Espasmos Infantis/complicações , Deficiência de Vitamina B 12/complicações , Asfixia Neonatal/complicações , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/sangue , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/urina , Feminino , Homocisteína/sangue , Humanos , Lactente , Masculino , Ácido Metilmalônico/urina , Estudos Retrospectivos , Espasmos Infantis/sangue , Espasmos Infantis/etiologia , Espasmos Infantis/urina , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/etiologia , Deficiência de Vitamina B 12/urina
20.
Neonatology ; 114(3): 253-260, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29961068

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) is the standard neuroimaging technique to assess perinatal asphyxia-associated brain injury in full-term infants. Diffusion-weighted imaging (DWI) is most informative when assessed during the first week after the insult. OBJECTIVES: To study the DWI abnormalities of the thalamus and basal ganglia in full-term infants with perinatal asphyxia. METHODS: Fifty-five (near) term infants (normothermia n = 23; hypothermia n = 32) with thalamus and/or basal ganglia injury were included. MRI findings were assessed visually and quantitatively calculating apparent diffusion coefficient (ADC) values. Thalamus/basal ganglia ADC ratios were calculated to analyze the differences between these areas. Infants with an early MRI (days 1-3) or later MRI (days 4-7) were compared. RESULTS: Isolated extensive thalamic injury was seen early, and focal thalamic and basal ganglia injury was seen later. On the early MRI, visual assessment underestimated abnormalities in the basal ganglia (59% abnormal vs. 90% abnormal on quantitative assessment; p = 0.015), suggesting the need for quantitative assessment. In infants treated with hypothermia, the thalamus/basal ganglia ADC ratio was lower. CONCLUSIONS: Both visual analysis and quantitative evaluation of cerebral MRI after perinatal asphyxia are needed, especially during the first few days after birth. Timing of ADC changes is influenced by therapeutic hypothermia.


Assuntos
Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Gânglios da Base/diagnóstico por imagem , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Hipotermia Induzida , Tálamo/diagnóstico por imagem , Gânglios da Base/patologia , Lesões Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Análise de Regressão , Estudos Retrospectivos , Tálamo/patologia
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