background Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain. methods We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability. results Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). conclusions Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic–ischemic encephalopathy.

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Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.

Background Newborn animal and human pilot studies suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae, without adverse effects. Objectives To determine whether therapeutic hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and long-term neurodevelopmental disability, without clinically important side effects. Search strategy The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library (Issue 2, 2003) was used. Randomised controlled trials evaluating therapeutic hypothermia in term newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue Issue 2, 2003), MEDLINE (1966 to July 2003), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching. Selection criteria Randomised controlled trials comparing the use of therapeutic hypothermia with normothermia in encephalopathic newborn infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies were included. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Data collection and analysis Three reviewers independently selected, assessed the quality of and extracted data from the included studies. Authors were contacted for further information. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Main results Two randomised controlled trials were included in this review, comprising 50 term infants with moderate/ severe encephalopathy and evidence of intrapartum asphyxia. There was no significant effect of therapeutic hypothermia on the combined outcome of death or major neurodevelopmental disability in survivors followed. No adverse effects of hypothermia on short term medical outcomes or on some 'early' indicators of neurodevelopmental outcome were detected. Reviewer's conclusions Although two small randomised controlled trials demonstrated neither evidence of benefit or harm, current evidence is inadequate to assess either safety or efficacy of therapeutic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. Therapeutic hypothermia for encephalopathic asphyxiated newborn infants should be further evaluated in well designed randomised controlled trials.

Cooling for newborns with hypoxic ischaemic encephalopathy.

Background Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain. Methods We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5°C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes. Results Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of su...

/pdf/moderate-hypothermia-to-treat-perinatal-asphyxial-3ks4z7fiy7.pdf

Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

https://www.ilcor.org/data/Post-cardiac_arrest_syndrome.pdf

Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication ☆ ☆☆ ★: A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke

The contributors to this statement were selected to ensure expertise in all the disciplines relevant to post–cardiac arrest care. In an attempt to make this document universally applicable and generalizable, the authorship comprised clinicians and scientists who represent many specialties in many regions of the world. Several major professional groups whose practice is relevant to post–cardiac arrest care were asked and agreed to provide representative contributors. Planning and invitations took place initially by e-mail, followed a series of telephone conferences and face-to-face meetings of the cochairs and writing group members. International writing teams were formed to generate the content of each section, which corresponded to the major subheadings of the final document. Two team leaders from different countries led each writing team. Individual contributors were assigned by the writing group cochairs to work on 1 or more writing teams, which generally reflected their areas of expertise. Relevant articles were identified with PubMed, EMBASE, and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Drafts of each section were written and agreed on by the writing team authors and then sent to the cochairs for editing and amalgamation into a single document. The first draft of the complete document was circulated among writing team leaders for initial comment and editing. A revised version of the document was circulated among all contributors, and consensus was achieved before submission of the final version for independent peer review and approval for publication.

This scientific statement outlines current understanding and identifies knowledge gaps in the pathophysiology, treatment, and prognosis of patients who regain spontaneous circulation after cardiac arrest. The purpose is to provide a resource for optimization of post–cardiac arrest care and to pinpoint the need for research focused on gaps in knowledge that would potentially improve outcomes …

Post–Cardiac Arrest Syndrome

https://umanitoba.ca/faculties/health_sciences/medicine/units/pediatrics/sections/neonatology/media/hypothermia8.pdf

Moderate hypothermia in neonatal encephalopathy: efficacy outcomes.

The use of hypothermia: a role in the treatment of neonatal asphyxia?

We report on a newborn infant with multiple congenital anomalies and apparent nonmosaic trisomy 9 in the blood (by conventional cytogenetic studies) who died shortly after birth. Clinical observations at birth and autopsy are compared with phenotypes of mosaic and nonmosaic trisomy 9 cases reported previously. Unlike the initial cytogenetic analysis, fluorescence in situ hybridization (FISH) studies of metaphase and interphase blood cells and skin fibroblasts detected the presence of euploid and trisomy 9 cells. These results suggest that earlier reports of trisomy 9, which relied on conventional chromosome analysis of a few metaphase cells and/or only one tissue type, may not have excluded mosaicism, and that trisomy 9 may be viable only in the mosaic state.

Mosaic vs. nonmosaic trisomy 9: report of a liveborn infant evaluated by fluorescence in situ hybridization and review of the literature.

Surfactant treatment has become the standard of care in premature infants with respiratory distress syndrome (RDS). Pulmonary hemorrhage, pulmonary edema, pneumonia, and atelectasis have been shown to liberate inflammatory mediators and plasma proteins, which damage type II pneumocytes and inactivate surfactant. These disease processes may, therefore, lead to a secondary surfactant inactivation or deficiency, which can be an unrecognized cause of respiratory decompensation after initial recovery from RDS in this vulnerable population. This is a descriptive report of three cases, which had acute respiratory decompensation between 1 and 3 weeks of age. All three infants demonstrated a response to secondary doses of surfactant. We submit that the diagnosis and treatment of secondary surfactant deficiency in the critically ill premature neonate warrants further study.

Secondary Surfactant Deficiency in Neonates

A composition, comprising an amount of VEGF-C sufficient to stimulate lymphatic angiogenesis in an intestine is provided. A method of stimulating intestinal maturation in a premature infant, comprising administering to the infant an amount of the VEGF-C-containing composition sufficient to cause lymphatic angiogenesis in the infant's intestine is provided. A composition, comprising an amount of VEGF sufficient to stimulate vascular angiogenesis in an intestine is provided. A method of stimulating intestinal maturation in a premature infant, comprising administering to the infant an amount of the VEFG-containing composition sufficient to cause vascular angiogenesis in the infant's intestine is also provided.

Dorothea J. Eicher

Papers

Moderate hypothermia in neonatal encephalopathy: efficacy outcomes.

The use of hypothermia: a role in the treatment of neonatal asphyxia?

Mosaic vs. nonmosaic trisomy 9: report of a liveborn infant evaluated by fluorescence in situ hybridization and review of the literature.

Secondary Surfactant Deficiency in Neonates

Vegf and vegf-c as infant formula supplements