***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND : The impact of treating electrographic seizures in hypoxic ischemic encephalopathy ( HIE ) is unknown . METHODS : Neonates ≥36 weeks with moderate or severe HIE were r and omly assigned to either treatment of electrographic seizures alone ( ESG ) or treatment of clinical seizures ( CSG ) . Conventional EEG video was monitored in both groups for up to 96 hours . Cumulative electrographic seizure burden ( SB ) was calculated in seconds and converted to log units for analysis . MRI scans were scored for severity of brain injury . Infants underwent neurodevelopmental evaluation at 18 to 24 months . Statistical analyses were performed by using SAS 9.3 version ( SAS Institute , Inc , Cary , NC ) . RESULTS : Thirty-five of 69 neonates ( 51 % ) who were r and omly assigned and included in the study developed seizures ( 15 in ESG and 20 in CSG ) . Excluding infants with status epilepticus , median SB ( interquartile range ) in seconds in ESG ( n = 10 ) was lower than in CSG ( n = 16 ) ( 449 [ 113–2070 ] vs 2226 [ 760–7654 ] ; P = .02 ) . ESG had fewer seizures with shorter time to treatment ( P = .04 ) . Twenty-four of 30 ( 80 % ) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months . Increasing SB in the combined cohort was significantly associated with higher brain injury scores ( P < .03 ) and lower performance scores across all 3 domains on BSID III ( P = .03 ) . CONCLUSIONS : In neonates with HIE  , EEG monitoring and treatment of electrographic seizures results in significant reduction in SB . SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III OBJECTIVE . The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy . METHODS . A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings , assigned r and omly to head cooling  for 72 hours , starting within 6 hours after birth ( with the rectal temperature maintained at 34.5 ± 0.5 ° C ) , or conventional care , were studied . Death or severe disability at 18 months of age was assessed in a multicenter , r and omized , controlled study ( the CoolCap trial ) . RESULTS . Treatment , lower encephalopathy grade , lower birth weight , greater amplitude-integrated electroencephalographic amplitude , absence of seizures , and higher Apgar score , but not gender or gestational age , were associated significantly with better outcomes . In a multivariate analysis , each of the individually predictive factors except for Apgar score remained predictive . There was a significant interaction between treatment and birth weight , categorized as ≥25th or < 25th percentile for term , such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling . For larger infants , the number needed to treat was 3.8 . Pyrexia ( ≥38 ° C ) in control infants was associated with adverse outcomes . Although there was a small correlation with birth weight , the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy . CONCLUSIONS . Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy . The protective effect of hypothermia was greater in larger infants OBJECTIVE To examine whether neonatal seizures are associated with neurodevelopmental outcomes in infants with hypoxia-ischemia independent of the presence and severity of brain injury seen on magnetic resonance imaging ( MRI ) . STUDY DESIGN We used multivariate regression to examine the independent effect of clinical neonatal seizures and their treatment on neurodevelopment in 77 term newborns at risk for hypoxic-ischemic brain injury . Clinical seizures were recorded prospect ively , and high-resolution newborn MRI measured the severity of brain injury . The outcome measure was the Full-Scale Intelligence Quotient ( FSIQ ) of the Wechsler Preschool and Primary Scale of Intelligence-Revised and neuromotor score at age 4 years . RESULTS After controlling for severity of injury on MRI , the children with neonatal seizures had worse motor and cognitive outcomes compared with those without seizures . The magnitude of effect varied with seizure severity ; children with severe seizures had a lower FSIQ than those with mild/moderate seizures ( P < .0001 ) . CONCLUSIONS Clinical neonatal seizures in the setting of birth asphyxia are associated with worse neurodevelopmental outcome , independent of the severity of hypoxic-ischemic brain injury . R and omized controlled trials are needed to determine whether differences in seizure treatment can improve outcome In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias A double blind r and omized study has been performed in 17 newborn infants bearing a diagnosis of perinatal asphyxia and treated with phenobarbital ( FB ) or phenytoin ( DPH ) to prevent the onset of seizures . The initial dose for both drugs was 12 m/kg IM the first day , followed by 6 mg/kg/day through the seventh day . Patients were clinical ly assessed daily and drug blood levels were also determined daily by enzyme immunoassay ( EMIT ) . Mean FB levels along the seven days were 17.6 , 23.7 , 25.6 , 31.6 , 31.4 , 36.7 , and 44.6 micrograms/ml . One child treated with FB exhibited seizures on the second day and six children showed drowsiness and bradycardia on the last two days , that were attributable to high levels of FB . Mean ( DPH ) levels along the study were : 4.6 , 7.0 , 9.7 , 6.5 , 4.5 , and 5.2 micrograms/ml . Seizures occurred in one of the DPH-treated patients and signs of therapeutic inefficacy such as hypertonus and abnormal movements appeared in four children OBJECTIVE To determine whether 40 mg/kg phenobarbital given to term infants with severe asphyxia would result in a lower incidence of seizures in the newborn period and an improved neurologic outcome . METHODS We conducted a r and omized , controlled , prospect i ve study . Entry criteria included ( 1 ) an initial arterial pH less than or equal to 7.0 with a base deficit 15 mEq/L or more , ( 2 ) Apgar score less than or equal to 3 at 5 minutes of age , or ( 3 ) failure to initiate spontaneous respiration by 10 minutes of age . Sample size was calculated to detect a 50 % reduction in the incidence of neonatal seizures . RESULTS No differences were present between treatment and control groups with respect to severity of asphyxia assessed by initial arterial pH , base excess , cerebrospinal fluid lactate dehydrogenase concentration or detection of CSF creatine kinase of its BB isoenzyme . Seizures occurred in 9 of 15 infants in the treatment group and 14 of 16 infants in the control group ( p = 0.11 ) . No adverse effects were observed from phenobarbital on heart rate , respiratory rate , blood pressure , or arterial blood gas values . Three-year follow-up revealed normal outcome in 11 of 15 infants in the treatment group and 3 of 16 in the control group ( p = 0.003 ) . CONCLUSION Phenobarbital , when administered in a dose of 40 mg/kg intravenously over 1 hour in term , severely asphyxiated newborn infants appeared to be safe and was associated with a 27 % reduction in the incidence of seizures and a significant improvement in neurologic outcome at 3 years of age It remains controversial as to whether neonatal seizures have additional direct effects on the developing brain separate from the severity of the underlying encephalopathy . Using data collected from infants diagnosed with hypoxic-ischemic encephalopathy , and who were enrolled in an National Institute of Child Health and Human Development trial of hypothermia , we analyzed associations between neonatal clinical seizures and outcomes at 18 months of age . Of the 208 infants enrolled , 102 received whole body hypothermia  and 106 were controls .  Clinical seizures were generally noted during the first 4 days of life and rarely afterward . When adjustment was made for study treatment and severity of encephalopathy , seizures were not associated with death , or moderate or severe disability , or lower Bayley Mental Development Index scores at 18 months of life . Among infants diagnosed with hypoxic-ischemic encephalopathy , the mortality and morbidity often attributed to neonatal seizures can be better explained by the underlying severity of encephalopathy A double‐blind trial with chloral hydrate and diazepam in the treatment of cerebral irritation in the newborn is described . Both drugs were found to be effective in controlling symptoms but more side‐effects were observed with chloral hydrate than with diazepam . The most significant finding related to weight gain .  Babies treated with diazepam had a mean weight gain of + 0.03 kg on the fourth day of life , whereas those treated with chloral hydrate had a mean weight loss of ‐0.15 kg ( p<0.02 ) . It is suggested that diazepam should be the drug of choice in the treatment of cerebral irritation in the newborn Objective To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia . Design Open label , R and omized controlled trial . Setting Neonatal intensive care unit of a tertiary care teaching hospital . Participants 72 full term inborn neonates with severe birth asphyxia . Methods Neonates were r and omized to Study  ( phenobarbital )  group and Control group . The infants in the study group received phenobarbital infusion ( 40mg/kg ) within first two hours of life while babies in the control group did not receive any phenobarbital . Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy . A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase , glutathione peroxidise and malonyldialdehyde . 60 neonates were followed up at 1 month of age when a detailed neurological examination was done . Results Four neonates in the study group and six neonates in the control group died during the study . Two neonates in the study group were lost to follow up . The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group . The neurological outcome at one month follow up was found to be comparable between the two groups . Conclusion Phenobarbital ( 40mg/kg ) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life BACKGROUND Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia . We did a multicentre r and omised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy . METHODS 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography ( aEEG ) were r and omly assigned to either head cooling for 72 h , within 6 h of birth , with rectal temperature maintained at 34 - 35 degrees C ( n=116 ) , or conventional care ( n=118 ) . Primary outcome was death or severe disability at 18 months . Analysis was by intention to treat . We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before r and omisation -- ie , severe loss of background amplitude , and seizures-- and those with less severe changes . FINDINGS In 16 babies , follow-up data were not available . Thus in 218 infants ( 93 % ) , 73/110 ( 66 % ) allocated conventional care and 59/108 
    Output:
    
We found only low or very low quality evidence addressing the use of prophylactic barbiturates in infants with perinatal asphyxia .
Although the administration of prophylactic barbiturate therapy to infants following perinatal asphyxia did reduce the risk of seizures , there was no reduction seen in mortality and there were few data addressing long-term outcomes .