human
***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: The objective of the study is to determine perinatal and postnatal factors that may affect the occurrence of  small cerebellar hemorrhage ( CBH )  and to evaluate the effect of small CBH on neurodevelopmental outcome in very preterm infants . This prospect i ve study in an unselected cohort of very preterm infants was approved by the medical ethics committee , and informed parental consent was obtained . Presence of small CBH ( < 4 mm ) was assessed with magnetic resonance imaging around term equivalent age in 108 preterm infants ( < 32 weeks gestation ) . We compared infants with and without small CBH for perinatal and postnatal factors , supratentorial brain injury , and for neurodevelopmental outcome at 2 years corrected age . Follow-up consisted of a neurological examination , mental and developmental assessment ( Bayley Scales of Infant Development ) , and behavior checklist . Univariate and multivariate logistic regression analyses were performed to examine the relationships between variables .  Small CBH  was diagnosed in 16/108 very preterm infants . Univariate analyses identified gestational age , high-frequency oscillation ( HFO ) ventilation , and grade 3–4 intraventricular hemorrhage ( IVH ) as factors associated with small CBH . HFO ventilation and severe IVH were independent predictors of small CBH . We found no association between small CBH and neurodevelopmental outcome at 2 years of age . Small CBH is a frequent finding in preterm infants . These hemorrhages are independently associated with HFO ventilation and severe supratentorial hemorrhage and seem to have a favorable short-term prognosis Abstract The optimum caffeine dose in preterm infants has not been well investigated . We aim ed to compare the efficacy and safety of high versus low-dose caffeine citrate on  apnea of prematurity ( AOP )  and successful extubation of preterm infants from mechanical ventilation . We compared high-dose ( loading 40 mg/kg/day and maintenance of 20 mg/kg/day ) versus low-dose ( loading 20 mg/kg/day and maintenance of 10 mg/kg/day ) caffeine citrate in preterm infants < 32 weeks gestation , presented with AOP within the first 10 days of life . A total of 120 neonates ( 60 in each group ) were enrolled . High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants ( p < 0.05 ) , the frequency of apnea ( p < 0.001 ) , and days of documented apnea ( p < 0.001 ) . High-dose caffeine was associated with significant increase in episodes of tachycardia ( p < 0.05 ) without a significant impact on physician decision to withhold caffeine . Conclusion : The use of higher , than current st and ard , dose of caffeine may decrease the chance of extubation failure in mechanically ventilated preterm infants and frequency of AOP without significant side effects . What is Known:• Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years . The optimal loading and maintenance dose of caffeine in preterm infants is not well-studied . What is New:• This double blind r and omized controlled trial demonstrated that using a higher , than current st and ard , loading and maintenance doses of caffeine for treatment of apnea in preterm infants is well tolerated and significantly decrease the frequency of apnea Background : St and ard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging ( MRI ) . We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development . Methods : Seventy-four preterm infants ( ≤30 wk gestational age ) were r and omly assigned to either a high ( 80 mg/kg i.v . ) or st and ard ( 20 mg/kg i.v . ) loading dose of caffeine citrate in the first 24 h of life . MRI and neurobehavioral testing were undertaken at term equivalent age . Infants returned at 2 y of age for developmental testing . Results : Clinical characteristics were similar between groups , with the exception of higher maternal age in the high-dose caffeine group . There was an increased incidence of cerebellar hemorrhage in infants r and omized to high-dose caffeine ( 36 vs. 10 % , P = 0.03 ) . Infants in the high-dose caffeine group also demonstrated more hypertonicity ( P = 0.02 ) and more deviant neurologic signs ( P = 0.04 ) at term equivalent age . Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups . Conclusion : Preterm infants r and omized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance . The results of this pilot trial discourage a larger r and omized controlled trial OBJECTIVE To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight ( ELBW ; 501 - 1000 g ) infants . STUDY DESIGN Retrospective analysis of prospect ively collected data from 5364 infants with a birthweight of 501 to 1000 g born at National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network centers from 1995 to 1998 . The main outcome measures were : survival , duration of mechanical ventilation , and neurodevelopmental outcome . RESULTS Overall survival was 71 % . The median duration of ventilation for survivors was 23 days ; 75 % were free of mechanical ventilation by 39 days , and 7 % were ventilated for > or = 60 days . Of those ventilated for > or = 60 days , 24 % survived without impairment . Of those ventilated for > or = 90 days , only 7 % survived without impairment . Of those ventilated > or = 120 days , all survivors were impaired . CONCLUSIONS The prognosis for ELBW with protracted ventilation remains grim . The cohort who remain intubated have diminished survival and high rates of impairment . Parents of these infants should be informed of changes in prognosis as the time of ventilation increases In an attempt to determine physiologic responses to neonatal apnea , we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity . Of these episodes , 832 ( 39.9 % ) were central , 1032 ( 49.6 % ) were mixed , and 218 ( 10.5 % ) were obstructive . Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment , and the decrease in saturation was correlated with preapnea saturation . The baseline heart rate was similar for all apnea types . Infants receiving doxapram had a lower baseline heart rate ( 137.8 + /- 10.5 beats/min ) than did infants receiving no therapy ( 142.8 + /- 16.6 beats/min ) and infants receiving theophylline ( 149.7 + /- 15.0 beats/min ) ( p = < 0.001 ) . A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events , and in infants who were not receiving therapy . Falls in heart rate were significantly less in infants receiving doxapram ( 27.8 % + /- 18.0 % ) than in infants receiving theophylline ( 44.5 % + /- 19.0 % ) or no therapy ( 48.4 % + /- 18.3 % ) ( p = < 0.001 ) . The most common heart rate pattern overall was a gradual decrease interrupted by accelerations , whereas an initial heart rate acceleration was the most common pattern in obstructive apnea . We conclude that heart rate response to  neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea To study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea Objective : To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects . Design : A multicentre , r and omised , double blind , clinical trial . Setting : Four tertiary neonatal units within Australia . Patients : Infants born less than 30 weeks gestation ventilated for more than 48 hours . Interventions : Two dosing regimens of caffeine citrate ( 20 v 5 mg/kg/day ) for periextubation management . Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation . Main outcome measure : Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or  doxapram  within seven days of caffeine loading . Results : A total of 234 neonates were enrolled . A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group ( 15.0 % v 29.8 % ; relative risk 0.51 ; 95 % confidence interval ( CI ) 0.31 to 0.85 ; number needed to treat 7 ( 95 % CI 4 to 24 ) ) . A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine ( mean ( SD ) days 14.4 ( 11.1 ) v 22.1 ( 17.1 ) ; p = 0.01 ) . No difference in adverse effects was detected in terms of mortality , major neonatal morbidity , death , or severe disability or general quotient at 12 months . Conclusions : This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period , without evidence of harm in the first year of life OBJECTIVE To investigate the relationship between the severity-based definition of bronchopulmonary dysplasia ( BPD ) , choice of treatment , and neurocognitive outcomes at age 3 and 8 years . DESIGN This is a secondary analysis of data collected from a prospect i ve , longitudinal sample of 99 children with a history of BPD . SETTING Children born with BPD admitted to 3 hospitals from February 1 , 1989 , to November 31 , 1991 . PARTICIPANTS Ninety-nine children with BPD were longitudinally assessed at age 3 and 8 years . Three severity groups ( mild , moderate , and severe ) were formed based on gestational age and need for supplemental oxygen therapy . MAIN EXPOSURES Supplemental oxygen therapy for 28 days or longer , birth weight less than 1500 g , and radiographic evidence of lung disease . MAIN OUTCOME MEASURES Neurologic and medical outcomes ; type of medical management ; and language , achievement , and cognitive functioning were compared among the 3 severity groups . RESULTS Severity classification of BPD was associated with poorer outcomes . Compared with children with mild or moderate BPD , children with severe BPD performed more poorly on IQ tests ( Mental Development Index , 90 vs 76.4 ; and Psychomotor Development Index , 92.5 vs 73.9 ) and language measures ( total , 95 vs 82 ) at age 3 years and performance IQ ( 86 vs 75 ) and perceptual organization ( 86 vs 76 ) at age 8 years . Severity of BPD was not associated with choice of medical management but was related to educational interventions . Children with severe BPD received more special education services ( 69 % vs 44 % ) than did children with mild BPD . CONCLUSIONS The severity-based classification clarifies the relationship between BPD and developmental sequelae . Children with severe BPD required more interventions at age 8 years than did children with mild or moderate BPD Caffeine , in the dose usually recommended ( 12.5 mg/kg loading dose and 3 mg/kg daily maintenance ) , and a higher dose regimen ( 25 mg/kg loading and 6 mg/kg daily maintenance ) , was compared with theophylline ( 7.5 mg/kg loading and 3 mg/kg thrice daily maintenance ) . The study was a r and omised controlled trial in the treatment of a group of 44 infants of less than 31 weeks ' gestation ( mean gestational age 28.3 weeks ) who were suffering from frequent apnoeic attacks .  All three regimens produced a significant reduction in apnoeic attacks within 24 hours , but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours . The use of caffeine for the treatment of neonatal apnoea is recommended , because a once daily dose is more easily administered , and because it was found that plasma concentrations were more predictable than those of theophylline . If used in very preterm infants , however , its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response BACKGROUND Methylxanthine therapy is commonly used for apnea of prematurity but in the absence of adequate data on its efficacy and safety . It is uncertain whether methylxanthines have long-term effects on neurodevelopment and growth . METHODS We r and omly assigned 2006 infants with birth 
    Output:
    
agent
***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: The objective of the study is to determine perinatal and postnatal factors that may affect the occurrence of  small cerebellar hemorrhage ( CBH )  and to evaluate the effect of small CBH on neurodevelopmental outcome in very preterm infants . This prospect i ve study in an unselected cohort of very preterm infants was approved by the medical ethics committee , and informed parental consent was obtained . Presence of small CBH ( < 4 mm ) was assessed with magnetic resonance imaging around term equivalent age in 108 preterm infants ( < 32 weeks gestation ) . We compared infants with and without small CBH for perinatal and postnatal factors , supratentorial brain injury , and for neurodevelopmental outcome at 2 years corrected age . Follow-up consisted of a neurological examination , mental and developmental assessment ( Bayley Scales of Infant Development ) , and behavior checklist . Univariate and multivariate logistic regression analyses were performed to examine the relationships between variables .  Small CBH  was diagnosed in 16/108 very preterm infants . Univariate analyses identified gestational age , high-frequency oscillation ( HFO ) ventilation , and grade 3–4 intraventricular hemorrhage ( IVH ) as factors associated with small CBH . HFO ventilation and severe IVH were independent predictors of small CBH . We found no association between small CBH and neurodevelopmental outcome at 2 years of age . Small CBH is a frequent finding in preterm infants . These hemorrhages are independently associated with HFO ventilation and severe supratentorial hemorrhage and seem to have a favorable short-term prognosis Abstract The optimum caffeine dose in preterm infants has not been well investigated . We aim ed to compare the efficacy and safety of high versus low-dose caffeine citrate on  apnea of prematurity ( AOP )  and successful extubation of preterm infants from mechanical ventilation . We compared high-dose ( loading 40 mg/kg/day and maintenance of 20 mg/kg/day ) versus low-dose ( loading 20 mg/kg/day and maintenance of 10 mg/kg/day ) caffeine citrate in preterm infants < 32 weeks gestation , presented with AOP within the first 10 days of life . A total of 120 neonates ( 60 in each group ) were enrolled . High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants ( p < 0.05 ) , the frequency of apnea ( p < 0.001 ) , and days of documented apnea ( p < 0.001 ) . High-dose caffeine was associated with significant increase in episodes of tachycardia ( p < 0.05 ) without a significant impact on physician decision to withhold caffeine . Conclusion : The use of higher , than current st and ard , dose of caffeine may decrease the chance of extubation failure in mechanically ventilated preterm infants and frequency of AOP without significant side effects . What is Known:• Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years . The optimal loading and maintenance dose of caffeine in preterm infants is not well-studied . What is New:• This double blind r and omized controlled trial demonstrated that using a higher , than current st and ard , loading and maintenance doses of caffeine for treatment of apnea in preterm infants is well tolerated and significantly decrease the frequency of apnea Background : St and ard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging ( MRI ) . We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development . Methods : Seventy-four preterm infants ( ≤30 wk gestational age ) were r and omly assigned to either a high ( 80 mg/kg i.v . ) or st and ard ( 20 mg/kg i.v . ) loading dose of caffeine citrate in the first 24 h of life . MRI and neurobehavioral testing were undertaken at term equivalent age . Infants returned at 2 y of age for developmental testing . Results : Clinical characteristics were similar between groups , with the exception of higher maternal age in the high-dose caffeine group . There was an increased incidence of cerebellar hemorrhage in infants r and omized to high-dose caffeine ( 36 vs. 10 % , P = 0.03 ) . Infants in the high-dose caffeine group also demonstrated more hypertonicity ( P = 0.02 ) and more deviant neurologic signs ( P = 0.04 ) at term equivalent age . Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups . Conclusion : Preterm infants r and omized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance . The results of this pilot trial discourage a larger r and omized controlled trial OBJECTIVE To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight ( ELBW ; 501 - 1000 g ) infants . STUDY DESIGN Retrospective analysis of prospect ively collected data from 5364 infants with a birthweight of 501 to 1000 g born at National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network centers from 1995 to 1998 . The main outcome measures were : survival , duration of mechanical ventilation , and neurodevelopmental outcome . RESULTS Overall survival was 71 % . The median duration of ventilation for survivors was 23 days ; 75 % were free of mechanical ventilation by 39 days , and 7 % were ventilated for > or = 60 days . Of those ventilated for > or = 60 days , 24 % survived without impairment . Of those ventilated for > or = 90 days , only 7 % survived without impairment . Of those ventilated > or = 120 days , all survivors were impaired . CONCLUSIONS The prognosis for ELBW with protracted ventilation remains grim . The cohort who remain intubated have diminished survival and high rates of impairment . Parents of these infants should be informed of changes in prognosis as the time of ventilation increases In an attempt to determine physiologic responses to neonatal apnea , we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity . Of these episodes , 832 ( 39.9 % ) were central , 1032 ( 49.6 % ) were mixed , and 218 ( 10.5 % ) were obstructive . Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment , and the decrease in saturation was correlated with preapnea saturation . The baseline heart rate was similar for all apnea types . Infants receiving doxapram had a lower baseline heart rate ( 137.8 + /- 10.5 beats/min ) than did infants receiving no therapy ( 142.8 + /- 16.6 beats/min ) and infants receiving theophylline ( 149.7 + /- 15.0 beats/min ) ( p = < 0.001 ) . A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events , and in infants who were not receiving therapy . Falls in heart rate were significantly less in infants receiving doxapram ( 27.8 % + /- 18.0 % ) than in infants receiving theophylline ( 44.5 % + /- 19.0 % ) or no therapy ( 48.4 % + /- 18.3 % ) ( p = < 0.001 ) . The most common heart rate pattern overall was a gradual decrease interrupted by accelerations , whereas an initial heart rate acceleration was the most common pattern in obstructive apnea . We conclude that heart rate response to  neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea To study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea Objective : To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects . Design : A multicentre , r and omised , double blind , clinical trial . Setting : Four tertiary neonatal units within Australia . Patients : Infants born less than 30 weeks gestation ventilated for more than 48 hours . Interventions : Two dosing regimens of caffeine citrate ( 20 v 5 mg/kg/day ) for periextubation management . Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation . Main outcome measure : Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or  doxapram  within seven days of caffeine loading . Results : A total of 234 neonates were enrolled . A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group ( 15.0 % v 29.8 % ; relative risk 0.51 ; 95 % confidence interval ( CI ) 0.31 to 0.85 ; number needed to treat 7 ( 95 % CI 4 to 24 ) ) . A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine ( mean ( SD ) days 14.4 ( 11.1 ) v 22.1 ( 17.1 ) ; p = 0.01 ) . No difference in adverse effects was detected in terms of mortality , major neonatal morbidity , death , or severe disability or general quotient at 12 months . Conclusions : This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period , without evidence of harm in the first year of life OBJECTIVE To investigate the relationship between the severity-based definition of bronchopulmonary dysplasia ( BPD ) , choice of treatment , and neurocognitive outcomes at age 3 and 8 years . DESIGN This is a secondary analysis of data collected from a prospect i ve , longitudinal sample of 99 children with a history of BPD . SETTING Children born with BPD admitted to 3 hospitals from February 1 , 1989 , to November 31 , 1991 . PARTICIPANTS Ninety-nine children with BPD were longitudinally assessed at age 3 and 8 years . Three severity groups ( mild , moderate , and severe ) were formed based on gestational age and need for supplemental oxygen therapy . MAIN EXPOSURES Supplemental oxygen therapy for 28 days or longer , birth weight less than 1500 g , and radiographic evidence of lung disease . MAIN OUTCOME MEASURES Neurologic and medical outcomes ; type of medical management ; and language , achievement , and cognitive functioning were compared among the 3 severity groups . RESULTS Severity classification of BPD was associated with poorer outcomes . Compared with children with mild or moderate BPD , children with severe BPD performed more poorly on IQ tests ( Mental Development Index , 90 vs 76.4 ; and Psychomotor Development Index , 92.5 vs 73.9 ) and language measures ( total , 95 vs 82 ) at age 3 years and performance IQ ( 86 vs 75 ) and perceptual organization ( 86 vs 76 ) at age 8 years . Severity of BPD was not associated with choice of medical management but was related to educational interventions . Children with severe BPD received more special education services ( 69 % vs 44 % ) than did children with mild BPD . CONCLUSIONS The severity-based classification clarifies the relationship between BPD and developmental sequelae . Children with severe BPD required more interventions at age 8 years than did children with mild or moderate BPD Caffeine , in the dose usually recommended ( 12.5 mg/kg loading dose and 3 mg/kg daily maintenance ) , and a higher dose regimen ( 25 mg/kg loading and 6 mg/kg daily maintenance ) , was compared with theophylline ( 7.5 mg/kg loading and 3 mg/kg thrice daily maintenance ) . The study was a r and omised controlled trial in the treatment of a group of 44 infants of less than 31 weeks ' gestation ( mean gestational age 28.3 weeks ) who were suffering from frequent apnoeic attacks .  All three regimens produced a significant reduction in apnoeic attacks within 24 hours , but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours . The use of caffeine for the treatment of neonatal apnoea is recommended , because a once daily dose is more easily administered , and because it was found that plasma concentrations were more predictable than those of theophylline . If used in very preterm infants , however , its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response BACKGROUND Methylxanthine therapy is commonly used for apnea of prematurity but in the absence of adequate data on its efficacy and safety . It is uncertain whether methylxanthines have long-term effects on neurodevelopment and growth . METHODS We r and omly assigned 2006 infants with birth 
    Output:
    