Hypothermia to Treat Neonatal Hypoxic Ischemic Encephalopathy

Department of Paediatrics, Mount Sinai Hospital, and University of Toronto, Ontario, M5G 1X5, Canada.
Archives of Pediatrics and Adolescent Medicine (Impact Factor: 5.73). 11/2007; 161(10):951-8. DOI: 10.1001/archpedi.161.10.951
Source: PubMed


To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [<or=32.0-33.5 degrees C] or mild [>or=33.6 degrees C]).
MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles.
Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up.
Systemic or selective head hypothermia compared with normothermia.
Death or moderate to severe neurodevelopmental disability.
Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign.
In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

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    • "The protective effects of hypothermia are attributed primarily to a reduction of apoptosis and of inflammation [12]. "
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    ABSTRACT: Our objective was to estimate the effect of therapeutic hypothermia on platelet count in neonates after perinatal asphyxia. We performed a retrospective case control study of all (near-) term neonates with perinatal asphyxia admitted between 2004 and 2012 to our neonatal intensive care unit. All neonates treated with therapeutic hypothermia were included in this study (hypothermia group) and compared with a historic control group of neonates with perinatal asphyxia treated before introduction of therapeutic hypothermia (2008). Primary outcome was thrombocytopenia during the first week after birth. Thrombocytopenia was found significantly more often in the hypothermia group than in the control group, 80% (43/54) versus 59% (27/46) (P = .02). The lowest mean platelet count in the hypothermia group and control group was 97 × 10(9)/L and 125 × 10(9)/L (P = .06), respectively, and was reached at a mean age of 4.1 days in the hypothermia group and 2.9 days in the control group (P < .001). The incidence of moderate/severe cerebral hemorrhage was 6% (3/47) in the hypothermia group versus 9% (3/35) in the control group (P = .64). In conclusion, neonates with perinatal asphyxia treated with therapeutic hypothermia are at increased risk of thrombocytopenia, without increased risk of cerebral hemorrhage.
    International Journal of Pediatrics 08/2014; 2014:760654. DOI:10.1155/2014/760654
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    • "The most successful and commonly used clinical treatment for HIE is head cooling or total body cooling [11-13], but limitations include the need to apply it early after the onset of HIE. When applied in the 6 h immediately after birth, hypothermia does reduce mortality, and it significantly reduces the incidence of moderate to severe neurodevelopmental disability [13,14]. "
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    ABSTRACT: While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid-base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.
    BMC Pregnancy and Childbirth 04/2014; 14(1):150. DOI:10.1186/1471-2393-14-150 · 2.19 Impact Factor
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    • "These larger clinical trials in human newborns described reproducible approaches to hypothermic therapies and confirmed the feasibility of such therapies [74,75,76,77]. In many of the experienced centers involved in the multicenter trials, hypothermia is becoming “standard care” [78]. "
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    ABSTRACT: Hypoxic-ischemic (HI) brain injury is one of the main causes of disabilities in term-born infants. It is the result of a deprivation of oxygen and glucose in the neural tissue. As one of the most important causes of brain damage in the newborn period, the neonatal HI event is a devastating condition that can lead to long-term neurological deficits or even death. The pattern of this injury occurs in two phases, the first one is a primary energy failure related to the HI event and the second phase is an energy failure that takes place some hours later. Injuries that occur in response to these events are often manifested as severe cognitive and motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of HI injury, there is an increasing need to find effective therapies as new opportunities for the reduction of brain damage and its long term effects. Some of these therapies are focused on prevention of the production of reactive oxygen species, anti-inflammatory effects, anti-apoptotic interventions and in a later stage, the stimulation of neurotrophic properties in the neonatal brain which could be targeted to promote neuronal and oligodendrocyte regeneration.
    03/2013; 3(1):191-214. DOI:10.3390/brainsci3010191
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