Early high-dose phenobarbital treatment for prevention of hypoxic-ischemic brain damage in very low birth weight infants (original) (raw)
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Perinatal Hypoxic-Ischemic Damage: Review of the Current Treatment Possibilities
Physiological Research, 2021
Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into...
MEDICC Review, 2021
INTRODUCTION Hypoxic ischemic encephalopathy is a neurological condition occurring immediately after birth following a perinatal asphytic episode. Therapeutic hypothermia is a safe and effective intervention to reduce mortality and major disability in survivors. In Latin America, perinatal asphyxia is a major problem, but no data are available characterizing its current situation in the region or the impact of hypoxic ischemic encephalopathy on its management. OBJECTIVE Understand the prevalence, mortality and use of therapeutic hypothermia in newborns at ≥36 weeks gestational age with hypoxic ischemic encephalopathy admitted to neonatal units reporting to the Ibero-American Society of Neonatology Network. METHODS The Ibero-American Society of Neonatology Network groups various neonatology centers in Latin America that share information and collaborate on research and medical care. We evaluated data on newborns with ≥36 weeks gestational age reported during 2019. Each unit received a guide with defi nitions and questions based on the Society's 7th Clinical Consensus. Evaluated were encephalopathy frequency and severity, Apgar score, need for resuscitation at birth, use of therapeutic hypothermia and clinical evolution at discharge. Our analysis includes descriptive statistics and comparisons made using the chi-square test. RESULTS We examined reports of 2876 newborns from 33 units and 6 countries. In 2849 newborns with available data, hypoxic encephalopathy prevalence was 5.1% (146 newborns): 27 (19%) mild, 36 (25%) moderate, 43 (29%) severe, and 40 (27%) of unknown intensity. In those with moderate and severe encephalopathy, frequencies of Apgar scores ≤3 at the fi rst minute (p = 0.001), Apgar scores ≤3 at the fi fth minute (p <0.001) and advanced resuscitation (p = 0.007) were higher. Therapeutic hypothermia was performed in only 13% of newborns (19). Neonatal mortality from encephalopathy was 42% (61). CONCLUSION Hypoxic ischemic encephalopathy is a neonatal condition that results in high mortality and severe neurological sequelae. In this study, the overall prevalence was 5.1% with a mortality rate of 42%. Although encephalopathy was moderate or severe in 54% of reported cases, treatment with hypothermia was not performed in 87% of newborns. These data refl ect a regional situation that requires urgent action.
Perinatal hypoxic-ischemic encephalopathy: severity determinants and outcomes
Perinatal hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological sequelae in later life. The aim of our study is to identify the factors that are associated with a higher degree of severity in HIE and evaluate the outcomes. We performed a retrospective study of all newborns with HIE treated at our neonatal intensive care unit (NICU) from January 2010 to December 2013. Data collected include information about prenatal period, peripartum period, demographic characteristics, admission and evolution during NICU stay and outcomes (assessed in three different times: at discharge, at 6-9 months and 18 months). Forty seven newborns were enrolled in our study, 11 (23.4%) with mild HIE, 21 (44.7%) with moderate HIE and 15 (31.9%) with severe HIE. Prenatal, perinatal and demographic data showed no statistically significant differences between groups. Statistically significant differences were found in values of Thompson score (p < 0.0001), abnormal aEEG/EEG at admission (p = 0.025) and at 48 hours (p = 0.018), need of mechanical ventilation (p = 0.004), acute renal failure (p = 0.002) and length of stay (p = 0.038) with high rates in the moderate and severe HIE groups. Regarding the outcomes, statistically significant differences were found in the prevalence of death (p = 0.010); need of antiepileptic drugs at discharge (p = 0.001); motor deficits requiring physiotherapy (p = 0.046), abnormal deep tendon reflex (p = 0.006) and need of antiepileptic drugs (p = 0.001) at 6-9 months follow-up; and cerebral palsy with cognitive impairment at 18 months (p = 0.041) with high rates in the severe HIE group. These results suggest that Thompson score, abnormal aEEG/EEG at admission and at 48 hours, mechanical ventilation, acute renal failure and length of stay are associated with more severe HIE. We also concluded that more severe HIE reflects worse outcomes whereas mild HIE is associated with normal outcome in the majority of patients at 18 months.
Neonatal Hypoxic-Ischemic Encephalopathy: a new view of an old problem
Neonatal hypoxic-ischemic encephalopathy (HIE) remains a challenge of perinatal medicine. It is an important cause of long term morbidity, including motor and behavio-ral deficits, mental retardation, seizures and cerebral palsy, and mortality in newborns. This paper reviews the patho-physiology and current concepts of the management of neo-natal HIE as well as the future potential neuroprotective strategies for attenuation of this disease.
Journal of Perinatology, 2012
Objective: To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia. Study Design: Records of 68 asphyxiated infants of X36 weeks' gestation, who received hypothermia for moderate or severe HIE were reviewed. Some of these infants received PB prophylactically or for clinical seizures. All surviving infants had later brain magnetic resonance imaging (MRI). The composite primary outcome of neonatal death related to HIE with worsening multiorgan dysfunction despite maximal treatment, and the presence of post-hypothermia brain MRI abnormalities consistent with hypoxic-ischemic brain injury, were compared between the infants who received PB before initiation of hypothermia (PB group, n ¼ 36) and the infants who did not receive PB before or during hypothermia (No PB group, n ¼ 32). Forward logistic regression analysis determined which of the pre-hypothermia clinical and laboratory variables predict the primary outcome. Result: The two groups were similar for severity of asphyxia as assessed by Apgar scores, initial blood pH and base deficit, early neurologic examination, and presence of an intrapartum sentinel event. The composite primary outcome was more frequent in infants from the PB group (PB 78% versus No PB 44%, P ¼ 0.006, odds ratio 4.5, 95% confidence interval 1.6 to 12.8). Multivariate analysis identified only the PB receipt before initiation of hypothermia (P ¼ 0.002, odds ratio 9.5, 95% confidence interval 2.3 to 39.5), and placental abruption to be independently associated with a worse primary outcome. Conclusion: PB treatment before cooling did not improve the composite outcome of neonatal death or the presence of an abnormal post-hypothermia brain MRI, but the long-term outcomes have not yet been evaluated.
Revista da Associacao Medica Brasileira (1992), 2017
Hypoxic ischemic encephalopathy is a major complication of perinatal asphyxia, with high morbidity, mortality and neurologic sequelae as cerebral palsy, mostly in poor or developing countries. The difficulty in the diagnosis and management of newborns in these countries is astonishing, thus resulting in unreliable data on this pathology and bad outcomes regarding mortality and incidence of neurologic sequelae. The objective of this article is to present a new clinical diagnostic score to be started in the delivery room and to guide the therapeutic approach, in order to improve these results.
A Comprehensive Clinical Approach to Hypoxic Ischaemic Encephalopathy in Term Infants: A Review
Acta Scientific Paediatrics, 2022
Introduction: Hypoxic ischemic encephalopathy (HIE) is the manifestation of multi-organ dysfunction after perinatal asphyxia. Out of 135 million live born babies in each year globally, there were 1.2million intrapartum still births, 717,000 intrapartum neonatal deaths, 1.15million cases of neonatal encephalopathy (NE), 287,000 neonatal deaths due to NE and 413,000 babies survived with neurodevelopmental impairment [1]. The incidence of HIE is 1-2 per 1000 births in rich countries and 10-20 per 1000 births [2] in low to middle income countries. Approximately ninety nine percent of HIE case related deaths are taking place in developing countries. It is a huge burden on these countries for tackling. The available trusted specific treatment, therapeutic hypothermia (HT) is less implemented and showed varied results of outcome. There was not much progress in preventing these deaths in low to middle income countries (LMIC). Methods: An online and manual literature search was conducted in November 2021 through PubMed, Cochrane library, Google Scholar, Online Google chrome search, texts and articles related to the title topic with keywords HIE, Post-resuscitation neonatal care, term infants, management and comprehensive approach. Articles were also collected from citations and references of the searched study papers. Search restricted to English language, free full text articles, human and neonates-term and late preterm. Animal studies and studies involving preterm infants were excluded. Eighteen study articles from PubMed, 17 articles from Cochrane library and another 22 articles relevant to the title topic were collected. These articles were analysed after going through the tile and abstract sections. Results: The collected study papers were narrated with the following subheadings-definition, pathophysiology, HIE staging, cooling criteria, cooling in High income countries (HIC), HIE and cooling in LMIC, HIE and therapeutic strategies at low resource setting (LRS), cooling HIE cases who do not fit into cooling criteria, newer potential therapeutic strategies for HIE, outcome predictors of HIE, counselling for parents, long-term health problems and conclusions. Definition: Asphyxia is a clinical condition that occurs from inadequate gas exchange and characterized by hypoxia, hypercarbia and acidosis. Perinatal asphyxia occurs during or prior to labour. Perinatal asphyxia is failure to initiate and sustain breathing at birth (World Health Organization 1997) [3]. HIE is the multi-organ manifestation after perinatal asphyxia. "NE is a syndrome of disturbed neurological function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a subnormal level of consciousness or seizures and often accompanied by difficulty with initiating and maintaining respiration and depression of tone and reflexes." [4].