***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury , but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth . This study reports a multicenter , r and omized , controlled , pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event . The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers , and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vinel and tests between normothermic and hypothermic groups . Thirty-two hypothermic and 33 normothermic neonates were enrolled . The entry criteria selected a severely affected group of neonates , with 77 % Sarnat stage III . Ten  hypothermia ( 10/32 , 31 % ) and 14 normothermia ( 14/33 , 42 % ) patients expired . Controlling for treatment group , outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers ( odds ratio 10.7 , 95 % confidence interval 1.3 - 90 ) . Severely abnormal motor scores ( Psychomotor Development Index < 70 ) were recorded in 64 % of normothermia patients and in 24 % of hypothermia patients . The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group ( 52 % ) than the normothermia group ( 84 % ) ( P = 0.019 ) . Although these results need to be vali date d in a large clinical trial , this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury Abstract Background There is now convincing evidence that in industrialized countries therapeutic hypothermia for  perinatal asphyxial encephalopathy increases survival with normal neurological function . However , the greatest burden of perinatal asphyxia falls in low and mid-re source setting s where it is unclear whether therapeutic hypothermia is safe and effective . Aims Under the UCL Ug and a Women 's Health Initiative , a pilot r and omized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital , a large public hospital with ~20,000 births in Kampala , Ug and a to determine : (i)The feasibility of achieving consent , neurological assessment , r and omization and whole body cooling to a core temperature 33 - 34 ° C using water bottles(ii)The temperature profile of encephalopathic infants with st and ard care(iii)The pattern , severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome (iv)The feasibility of neurodevelopmental follow-up at 18 - 22 months of age Methods / Design Ethical approval was obtained from Makerere Univer sity and Mulago Hospital . All infants were in-born . Parental consent for entry into the trial was obtained . Thirty-six infants were r and omized either to st and ard care plus cooling ( target rectal temperature of 33 - 34 ° C for 72 hrs , started within 3 h of birth ) or st and ard care alone . All other aspects of management were the same . Cooling was performed using water bottles filled with tepid tap water ( 25 ° C ) . Rectal , axillary , ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1 - 4 , a structured , scorable neurological examination and head circumference were performed on days 7 and 17 . Cranial ultrasound was performed on days 1 , 3 and 7 and scored . Griffiths developmental quotient , head circumference , neurological examination and assessment of gross motor function were obtained at 18 - 22 months . Discussion We will highlight differences in neonatal care and infrastructure that need to be taken into account when considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid re source setting s in the future . Trial registration Current controlled trials IS RCT OBJECTIVE To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS Twenty-six term infants with Apgar < or=6 at 5 minutes or cord/first arterial pH < 7.1 , plus evidence of encephalopathy , were studied . After parental consent had been obtained , 13 infants received selective head cooling with the rectal temperature maintained at 35.0 degrees C in 6 infants and at 34.5 degrees C in 7 infants . The remaining 13 infants were normothermic . Cooling was achieved by circulating water at 10 degrees C through a cap placed around the head . Rectal , fontanelle , and nasopharyngeal temperatures were monitored . RESULTS One cooled infant died 2 days after rewarming , and 3 control infants died . Seizures occurred in 9 (69%)of 13 cooled infants and 5 ( 38 % ) of 13 control infants . Respiratory support within the first 72 hours of life was required in 10 of 13 infants in both the cooled and control groups . Three cooled infants and 1 control infant received nitric oxide for persistent pulmonary hypertension . During the same interval , 6 of the cooled infants and 4 of the control infants had episodes in which their blood pressure fell to < 40 mm Hg ; in 2 infants in each group , the lowest blood pressure was below 35 mm Hg . No requirement for volume expansion or increased inotropic support was seen in any infant during stepwise rewarming . All of the cooled infants demonstrated a fall in heart rate during cooling , but the rate was < 80/min in only 2 cases and no infant had a rate < 70/min . No infant demonstrated an abnormal rhythm or was clinical ly compromised by the change in heart rate . One infant cooled to a rectal temperature of 34.5 degrees C had a prolonged QT interval of 570 ms associated with a heart rate of 85/min on electrocardiogram aged 34 hours . This returned to normal after rewarming . Platelet counts below 150 x 10(9)/L , hypoglycemia below 2.6 mmol/L , and highest creatinine were not statistically different between cooled and control infants . Positive precooling blood cultures were found in 1 cooled and 1 control infant . The mean cap water input temperature used during cooling was 10 + /- 1 degrees C. During active cooling , the mean difference between rectal and nasopharyngeal temperature was 1.4 degrees C in the infants who were not receiving respiratory support , but this gradient could not be measured in those who were receiving respiratory support that involved delivery of warmed gases to the nasopharynx . CONCLUSIONS This study suggests that selective head cooling combined with mild systemic hypothermia of 34.4 degrees C or 35.0 degrees C is a stable , well-tolerated method of reducing cerebral temperature in term newborn infants after perinatal asphyxia Hypoxic-ischemic encephalopathy ( HIE ) remains one of the most important neurologic complications in the newborn . Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage . Furthermore , recent data have suggested that platelet-activating factor ( PAF ) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury . The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia . In addition , we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid ( CSF ) after hypoxic-ischemic brain injury . The group of asphyxiated infants ( Group 1 ) consisted of 21 full-term ( gestational age > 37 weeks ) . These infants were r and omized and divided into either a st and ard therapy group ( Group 1a ; n=10 ) or cooling group ( Group 1b ; n=11 ) . Head cooling combined with minimal hypothermia ( rectal temperature 36.5 - 36 degrees C ) was started as soon as practicable after birth . The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h . The control group ( Group 2 ) consisted of seven full-term infants and none of these infants showed any sign of asphyxia . To measure PAF concentration in CSF , CSF with lumbar puncture was collected into tubes immediately before the cooling ( 1 - 3h after birth ) and again after 36h . We had no evidence of severe adverse events related to hypothermia . In Group 1a , two infants died after 72h of life ; however , all newborn infants in Group 1b survived . Convulsion required treatment in three infants of st and ard therapy group ( 1a ) ; none of the infants in Group 1b had clinical seizure activity . Abnormal EEG patterns were found in four infants of Group 1a ; no EEG abnormalities were noted in Group 1b ( P<0.05 ) . On admission ( before cooling ) , PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control ( P<0.001 ) . Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups ( Group 1a vs. 1b ) ( P>0.05 ) . Obtained PAF level in CSF after 36h , showed a profound decline in cooling group of infants compared to Group 1a infants ( P<0.01 ) . In conclusion , the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging . Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants In intensive care setting s in the developed world , therapeutic hypothermia is established as a therapy for term infants with moderate to severe neonatal encephalopathy due to perinatal asphyxia . Several pre clinical , pilot and clinical trials conducted in such setting s over the last decade have demonstrated that this therapy is safe and effective . The greatest burden of birth asphyxia falls , however , in low- and middle-income countries ; it is still unclear whether therapeutic hypothermia is safe and effective in this context . In this paper , the issues around treatments that may be proven safe and effective in the developed world and the caution needed in translating these into different setting s and population s are explored . It is argued that there are strong scientific and ethical reasons supporting the conduct of rigorous , r and omised controlled trials of therapeutic hypothermia in middle-income setting s. There also needs to be substantial and sustainable improvements in all facets of antenatal care and in the basic level of newborn resuscitation in low income countries . This will reduce the burden of disease and allow health workers to determine rapidly which infants are most eligible for potential neuroprotection Objective To determine whether training  traditional birth attendants  to manage several common perinatal conditions could reduce  neonatal mortality in the setting of a re source poor country with limited access to healthcare . Design Prospect i ve , cluster r and omised and controlled effectiveness study . Setting Lufwanyama , an agrarian , poorly developed district located in the Copperbelt province , Zambia . All births carried out by study birth attendants occurred at mothers ’ homes , in rural village setting s. Participants 127 traditional birth attendants and mothers and their newborns ( 3559 infants delivered regardless of vital status ) from Lufwanyama district . Interventions Using an unblinded design , birth attendants were cluster r and omised to intervention or control groups . The intervention had two components : training in a modified version of the neonatal resuscitation protocol , and single dose amoxicillin coupled with facilitated referral of infants to a health centre . Control birth attendants continued their existing st and ard of care ( basic obstetric skills and use of clean delivery kits ) . Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth , with rate ratios statistically adjusted for clustering . Secondary outcomes were mortality at different time points ; and comparison of causes of death based on verbal autopsy data . Results Among 3497 deliveries with reliable information , mortality at day 28 after birth was 45 % lower among liveborn infants delivered by intervention birth attendants than control birth attendants ( rate ratio 0.55 , 95 % confidence interval 0.33 to 0.90 ) . The greatest reductions in mortality were in the first 24 hours after birth : 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants ( 0.40 , 0.19 to 0.83 ) . Deaths due to birth asphyxia were reduced by 63 % among infants delivered by intervention birth attendants ( 0.37 , 0.17 to 0.81 ) and by 81 % within the first two days after birth ( 0.19 , 0.0 
    Output:
    
Meta-regression revealed that hypothermia efficacy does not increase as the gross domestic product per capita rises .
There is enough evidence to support hypothermia as the st and ard care for hypoxic-ischemic encephalopathy .
Evidence from low-re source setting s is limited , but hypothermia efficacy was not shown to be associated with better re sources countries