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Therapeutic hypothermia in newborn

Divyen K Shah, Vennila Ponnusamy, Jane Evanson, Olga Kapellou, Georgia Ekitzidou, Neelam Gupta, Paul Clarke, Adina T Michael-Titus, Ping K Yip
Aims and hypothesis: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes...
2018: Frontiers in Neurology
Heather Campbell, Rathinaswamy B Govindan, Srinivas Kota, Tareq Al-Shargabi, Marina Metzler, Nickie Andescavage, Taeun Chang, Gilbert Vezina, Adre du Plessis, An N Massaro
OBJECTIVE: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. STUDY DESIGN: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia...
March 6, 2018: Journal of Pediatrics
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
Nazli Kuter, Nese Aysit-Altuncu, Gurkan Ozturk, Eren Ozek
BACKGROUND: In high-risk newborns indirect hyperbilirubinemia can lead to acute bilirubin encephalopathy and kernicterus. Despite the current therapeutic modalities, preventing or reversing the neurotoxicity cannot be achieved in all infants. OBJECTIVE: To investigate the neuroprotective effects of hypothermia on bilirubin-induced toxicity in primary mouse neuronal cell cultures. METHODS: Hippocampal cell cultures, isolated from newborn mouse brains, were incubated with unconjugated bilirubin (UCB) at 3 days in vitro (DIV) and immediately exposed to varying degrees of hypothermia...
March 6, 2018: Neonatology
Lina Chalak, Samantha Latremouille, Imran Mir, Pablo J Sánchez, Guilherme Sant'Anna
A review of the conundrum called mild hypoxic-ischemic encephalopathy (HIE) is provided. During the past decades, the definition of HIE has evolved to accommodate the short window of time required for the initiation of therapeutic hypothermia. Also, neurological evaluations have changed with the use of simpler staging systems that can be applied within the first 6 h of life. In this review, we discuss the challenges in the identification of newborns with "mild HIE" within 6 h after birth, the limitations in the existing early biomarkers of brain injury, and the current knowledge gaps in the long term neurodevelopmental outcomes of infants diagnosed with mild HIE...
March 2, 2018: Early Human Development
Satyan Lakshminrusimha, Seetha Shankaran, Abbot Laptook, Scott McDonald, Martin Keszler, Krisa Van Meurs, Ronnie Guillet, Sanjay Chawla, Beena G Sood, Sonia Bonifacio, Abhik Das, Rosemary D Higgins
OBJECTIVE: To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS: We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial...
March 1, 2018: Journal of Pediatrics
Brigitte Lemyre, Linh Ly, Vann Chau, Anil Chacko, Nicholas Barrowman, Hilary Whyte, Steven P Miller
Objective: To identify factors associated with early initiation and achievement of therapeutic hypothermia (TH) in newborns with hypoxic-ischemic encephalopathy (HIE). Methods: Retrospective cohort study of newborns who received TH according to National Institute of Child Health and Human Development (NICHD) criteria in two academic level 3 Neonatal Intensive Care Units (NICU) between 2009 and 2013. All infants were transported by a neonatal transport team (NNTT)...
August 2017: Paediatrics & Child Health
Isabel Benavente-Fernandez, Juan J Ramos-Rodriguez, Carmen Infante-Garcia, Gema Jimenez-Gomez, Alfonso Lechuga-Sancho, Simon Lubian-Lopez, Monica Garcia-Alloza
Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication responsible for ∼23% of all neonatal deaths. Also, 30-70% of these patients will suffer lifetime disabilities, including learning impairment, epilepsy or cerebral palsy. However, biomarkers for HIE screening, or monitoring disease progression are limited. Herein, we sought to evaluate the clinical usefulness of plasma-type gelsolin (pGSN) and amyloid-beta (Aβ) 40 and 42 as prognostic biomarkers for HIE. pGSN has been previously suggested as a feasible marker in other brain injuries and amyloid-beta 40 and 42 are classically assessed in neurodegenerative diseases...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Katsumi Hayakawa, Sachiko Koshino, Koichi Tanda, Akira Nishimura, Osamu Sato, Hiroyuki Morishita, Takaaki Ito
BACKGROUND: Pseudonormalization of diffusion-weighted magnetic resonance imaging (MRI) can lead to underestimation of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE), posing a significant problem. We have noticed that some neonates show pseudonormalization negativity on diffusion-weighted imaging. OBJECTIVE: To compare pseudonormalization negativity with clinical outcomes. MATERIALS AND METHODS: Seventeen term neonates with moderate or severe HIE underwent therapeutic hypothermia...
February 7, 2018: Pediatric Radiology
Hülya Özdemir, Aslı Memişoğlu, Zeynep Alp-Unkar, Baran Arcagök, Hülya Bilgen, Serap Turan, Eren Özek
Özdemir H, Memişoğlu A, Alp-Unkar Z, Arcagök B, Bilgen H, Turan S, Özek E. Persistent hyperglycemia in a neonate: Is it a complication of therapeutic hypothermia? Turk J Pediatr 2017; 59: 193-196. The aim of this report is to present a newborn with persistent hyperglycemia requiring insulin therapy as a possible complication of therapeutic hypothermia. A term appropriate for gestational age (AGA) female infant, was born by emergency cesarean section due to abruption of placenta and was resuscitated and intubated in the delivery room...
2017: Turkish Journal of Pediatrics
Niranjan Thomas, Thangaraj Abiramalatha, Vishnu Bhat, Manoj Varanattu, Suman Rao, Sanjay Wazir, Leslie Lewis, Umamaheswari Balakrishnan, Srinivas Murki, Jaikrishnan Mittal, Ashish Dongara, Y N Prashantha, Somashekhar Nimbalkar
OBJECTIVE: To assess the feasibility and safety of cooling asphyxiated neonates using phase changing material based device across different neonatal intensive care units in India. DESIGN: Multi-centric uncontrolled clinical trial. SETTING: 11 level 3 neonatal units in India from November 2014 to December 2015. PARTICIPANTS: 103 newborn infants with perinatal asphyxia, satisfying pre-defined criteria for therapeutic hypothermia...
December 14, 2017: Indian Pediatrics
Juan Arnaez, Alfredo Garcia-Alix, Sara Calvo, Simón Lubián-López
INTRODUCTION: The process of care and assistance from birth to the starting of therapeutic hypothermia (TH) is crucial in order to improve its effectiveness and prevent the worsening of hypoxic-ischaemic injury. METHODS: A national cross-sectional study carried out in 2015 by use of a questionnaire sent to all level iii units on the care of the newborn≥35 weeks gestation within the first hours of life after a perinatal asphyxia event. According to clinical practice guidelines, the quality of care was compared between the hospitals that carried out or did not carry out TH, and according to the level of care...
December 11, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
Renata Polackova, Dana Salounova, Lumir Kantor
AIMS: This prospective study aimed to evaluate the relationship between persistently elevated lactate values in the arterial blood of newborns with grade II and III hypoxic ischemic encephalopathy (treated with therapeutic hypothermia) and psychomotor development at 24 months. METHODS: 51 neonates of gestational age from 36 to 41 weeks receiving therapeutic hypothermia for moderate to severe hypoxic ischaemic encephalopathy had arterial blood lactate levels regularly analysed...
December 4, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Ángel Sánchez-Illana, Antonio Núñez-Ramiro, María Cernada, Anna Parra-Llorca, Eva Valverde, Dorotea Blanco, Maria Teresa Moral-Pumarega, Fernando Cabañas, Hector Boix, Antonio Pavon, Mercedes Chaffanel, Isabel Benavente-Fernández, Inés Tofe, Begoña Loureiro, José R Fernández-Lorenzo, Belén Fernández-Colomer, Ana García-Robles, Julia Kuligowski, Máximo Vento
Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points...
December 6, 2017: Scientific Reports
Viktória Kovács, Valéria Tóth-Szűki, János Németh, Viktória Varga, Gábor Remzső, Ferenc Domoki
AIMS: Perinatal asphyxia (PA) often results in hypoxic-ischemic encephalopathy (HIE) in term neonates. Introduction of therapeutic hypothermia improved HIE outcome, but further neuroprotective therapies are still warranted. The present study sought to determine the feasibility of the activation of the cytoprotective PI-3-K/Akt and the MAPK/ERK signaling pathways in the subacute phase of HIE development in a translational newborn pig PA/HIE model. MAIN METHODS: Phosphorylated and total levels of Akt and ERK were determined by Western blotting in brain samples obtained from untreated naive, time control, and PA/HIE animals at 24-48h survival (n=3-3-6,respectively)...
November 11, 2017: Life Sciences
Maria Agustina Lopez Laporte, Hui Wang, Priscille-Nice Sanon, Stephanie Barbosa Vargas, Julie Maluorni, Emmanouil Rampakakis, Pia Wintermark
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...
November 27, 2017: Journal of Maternal-fetal & Neonatal Medicine
Salwa Khedr, Anna Piskorski, Adrienne R Bingham, Justin Goldstein, Abbot R Laptook, Monique E De Paepe
Therapeutic hypothermia (head or whole-body cooling) improves survival and neurodevelopmental outcome in term newborns with moderate-to-severe encephalopathy. Hypothermia treatment is well tolerated; the most common side effect is thrombocytopenia. In about 1% of infants, focal subcutaneous fat necrosis has been reported. We describe a case of clinically unsuspected massive visceral fat necrosis in a term infant with Apgar score 0 at 1 min ("resuscitated apparently stillborn" infant) who was treated with therapeutic hypothermia for 72 h and expired on the 25th day of life following a neonatal course complicated by severe encephalopathy, pulmonary artery hypertension, persistent thrombocytopenia, hypoglycemia, and severe basal ganglia-thalamic abnormalities on magnetic resonance imaging...
January 1, 2017: Pediatric and Developmental Pathology
Ayham Alshweki, Alejandro Pérez-Muñuzuri, Olalla López-Suárez, Ana Baña, Maria L Couce
The initial diagnosis of neonatal hypoxic-ischemic encephalopathy is based on nervous system clinical manifestations. The use of biomarkers to monitor brain injury and evaluate neuroprotective effects allows early intervention and treatment. This study was designed to determine the short-term prognostic significance of urinary S100B calcium-binding protein (S100B) in asphyxiated newborns treated with hypothermia.An observational prospective study was conducted over a period of 5 years in 31 newborns with hypoxic-ischemic encephalopathy who received therapeutic hypothermia...
November 2017: Medicine (Baltimore)
Abbot R Laptook, Seetha Shankaran, Jon E Tyson, Breda Munoz, Edward F Bell, Ronald N Goldberg, Nehal A Parikh, Namasivayam Ambalavanan, Claudia Pedroza, Athina Pappas, Abhik Das, Aasma S Chaudhary, Richard A Ehrenkranz, Angelita M Hensman, Krisa P Van Meurs, Lina F Chalak, Shannon E G Hamrick, Gregory M Sokol, Michele C Walsh, Brenda B Poindexter, Roger G Faix, Kristi L Watterberg, Ivan D Frantz, Ronnie Guillet, Uday Devaskar, William E Truog, Valerie Y Chock, Myra H Wyckoff, Elisabeth C McGowan, David P Carlton, Heidi M Harmon, Jane E Brumbaugh, C Michael Cotten, Pablo J Sánchez, Anna Maria Hibbs, Rosemary D Higgins
Importance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy...
October 24, 2017: JAMA: the Journal of the American Medical Association
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