***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: Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials To test the hypothesis that restriction of sodium intake during the first 3 to 5 days of life will prevent the occurrence of hypernatremia and the need for administration of large fluid volumes , we prospect ively and r and omly assigned 17 babies ( mean + /- SD : 850 + /- 120 gm ; 27 + /- 1 weeks of gestation ) to receive in blind fashion either daily maintenance sodium or salt restriction with physician-prescribed parenteral fluid intake . Maintenance-group infants received 3 to 4 mEq of sodium per kilogram per day ; restricted infants received no sodium supplement other than with such treatments as transfusion . Sodium balance studies conducted for 5 days demonstrated that maintenance salt intake result ed in a daily sodium balance near zero , whereas sodium-restricted infants continued to excrete urinary sodium at a high rate , which promoted a more negative balance ( average daily sodium balance -0.30 + /- 1.78 SD in maintenance group vs -3.71 + /- 1.47 mEq/kg per day in restriction group ; p less than 0.001 ) . Care givers tended to prescribe daily increases in parenteral fluids for the salt-supplemented infants , perhaps because serum sodium concentrations were elevated in these infants after the first day of the study ( p less than 0.001 ) . Hypernatremia developed in two sodium-supplemented infants ( greater than 150 mEq/L ) , and hyponatremia developed in two sodium-restricted infants ( less than 130 mEq/L ) ; however , the restricted infants were more likely to have normal serum osmolality ( p less than 0.05 ) . Both groups of infants produced urine that was neither concentrated nor dilute , with a high fractional excretion of sodium ; renal failure was not observed . The mortality rate was not affected , but the incidence of bronchopulmonary dysplasia was significantly less in the sodium-restricted babies ( p less than 0.02 ) . We conclude that in tiny premature infants , a fluid regimen that restricts sodium may simplify parenteral fluid therapy targeted to prevent hypernatremia and excessive administration of parenteral fluids AIMS To compare the effects of early and delayed sodium supplementation on body composition and body water compartments during the first two weeks of postnatal life . METHODS Preterm infants of 25–30 weeks ' gestation were stratified and r and omly assigned according to gender and gestational age , to receive a sodium intake of 4 mmol/kg/day beginning either on the second day after birth or when weight loss of 6 % of birthweight had been achieved . Daily sodium intake , total fluid intake , energy intake , urine volume , and urinary sodium excretion were recorded . Total body water was measured by H2 18O dilution on days 1 , 7 , and 14 , and extracellular fluid volume by sodium bromide dilution on days 1 and 14 . RESULTS Twenty four infants received early , and 22 delayed , sodium supplementation .  There were no significant differences between the groups in body water compartments on day 1 . In the delayed group , but not the early group , there was a significant loss of total body water during the first week ( delayed −44 ml/kg , p=0.048 ; early 6 ml/kg , p=0.970 ) . By day 14 the delayed , but not the early group , also had a significant reduction in extracellular fluid volume ( delayed −53 ml/kg , p=0.01 ; early −37 ml/kg , p=0.2 ) . These changes result ed in a significant alteration in body composition at the end of the first week ( total body weight : delayed 791 ml/kg ; early 849 ml/kg , p=0.013 ) . By day 14 there were once again no significant differences in body composition between the two groups . CONCLUSIONS Body composition after preterm birth is influenced by the timing of introduction of routine sodium supplements . Early sodium supplementation can delay the physiological loss of body water that is part of normal postnatal adaptation . This is likely to be of particular relevance to babies with respiratory distress syndrome . A tailored approach to clinical management , delaying the introduction of routine sodium supplements until there has been postnatal loss of body water , is recommended OBJECTIVES Our purpose was to determine the mortality and morbidity rates for infants weighing 501 to 1500 g according to gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1993 through December 1994 by 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty-three percent of infants survived until discharge to home or to a long- term care facility ( compared with 74 % in 1988 ) . Survival to discharge was 49 % for infants weighing 501 to 750 g at birth , 85 % for those 751 to 1000 g , 93 % for those 1001 to 1250 g , and 96 % for those 1251 to 1500 g. The majority of deaths occurred within the first 3 days of life . Mortality rates were greater for male than for female infants . Respiratory distress syndrome was the most frequent pulmonary disease ( 52 % ) . Chronic lung disease ( defined as an oxygen requirement at 36 weeks after conception ) developed in 19 % . Thirty-two percent of infants had evidence of intracranial hemorrhage . Periventricular leukomalacia was noted in 6 % of infants who had ultrasonography after 2 weeks . The average duration of hospitalization for survivors was 68 days ( 122 days for surviving infants weighing 501 to 750 g , compared with an average of 43 days for surviving infants 1251 to 1500 g ) . Among infants who died , the average length of stay was 19 days . CONCLUSIONS The mortality rate for infants weighing between 501 and 1500 g at birth continues to decline . This increase in survival is not accompanied by an increase in medical morbidity . There are interactions between birth weight , gestational age , sex , and survival rates OBJECTIVES To determine the risk of bronchopulmonary dysplasia ( BPD ) in subgroups of infants with and without patent ductus arteriosus ( PDA ) who were r and omized to indomethacin prophylaxis or placebo  , and to examine whether adverse drug effects on edema formation and oxygenation may explain why indomethacin prophylaxis does not reduce BPD . STUDY DESIGN We studied 999 extremely low birth weight infants who participated in the Trial of Indomethacin Prophylaxis in Preterms ( TIPP ) and who survived to a postmenstrual age of 36 weeks . RESULTS The incidence of BPD in the 2 subgroups of infants with PDA was 52 % ( 55/105 ) after indomethacin prophylaxis and 56 % ( 137/246 ) after placebo . In contrast , rates of BPD in the 2 subgroups without a PDA were 43 % ( 170/391 ) after indomethacin prophylaxis and 30 % ( 78/257 ) after placebo ( P [ interaction ] = .015 ) . Logistic regression analysis with adjustment for prognostic baseline factors showed that adverse and independent effects of indomethacin prophylaxis on the need for supplemental oxygen and on weight loss by the end of the first week of life may increase the risk of BPD in infants without PDA . CONCLUSIONS Harmful side effects on oxygenation and edema formation may explain why indomethacin prophylaxis does not prevent BPD even though it reduces PDA We conducted a case-control study of antecedents of bronchopulmonary dysplasia ( BPD ) in 223 infants enrolled in a prospect i ve , r and omized clinical trial of phenobarbital prophylaxis for intracranial hemorrhage . The trial took place at three Boston neonatal intensive care units between June 1981 and April 1984 . The 76 babies with BPD had radiographic evidence of the condition and required oxygen therapy for 28 days or more . All 147 control babies survived until day 28 of life without meeting either of these criteria for BPD . Compared with control infants , those with BPD received greater quantities of total , crystalloid , and colloid fluids per kilogram per day in the first 4 days of life . In addition , infants with BPD generally had a net weight gain in the first 4 days of life in contrast to the normal pattern of weight loss seen in control infants . Finally , the infants with BPD were more likely to be given a clinical diagnosis of patent ductus arteriosus and to have received furosemide on days 3 and 4 of life . From these observations we infer that early postnatal phenomena such as excessive fluid therapy may be important in the pathogenesis of BPD OBJECTIVES Two multicenter r and omized controlled trials ( RCTs ) in premature infants ( Ment et al , 1994 and TIPP , 2001 ) found beneficial effects of indomethacin prophylaxis on the incidences of patent ductus arteriosus ( PDA ) , PDA ligation , and severe intracranial hemorrhage ( ICH ) . The Ment trial recommended the use of indomethacin prophylaxis . The TIPP trial failed to find a benefit in its primary outcome ( improved survival/neurodevelopmental outcome ) ; this negative result may have discouraged indomethacin prophylaxis use . STUDY DESIGN We used the National Institute of Child Health and Development 's Neonatal Network Registry to determine the association between the 2 trials and the use of indomethacin prophylaxis . We also statistically assessed the assumptions that led to the TIPP trial 's negative results . RESULTS Use of indomethacin prophylaxis among network clinicians increased after publication of the Ment trial and decreased after the TIPP trial . Analysis of the TIPP trial showed that the primary outcome 's anticipated effect size ( > or = 20 % ) was too large ; a smaller effect size ( < 3 % ) would have been more appropriate based on the incidence of ICH in their population and its association with neurodevelopmental outcome . CONCLUSIONS Two multicenter RCTs were associated with changes in  indomethacin prophylaxis . After the Ment trial , the use of  indomethacin prophylaxis increased . After the TIPP trial , which reported negative results based on an excessively large anticipated effect size , its use decreased OBJECTIVES To determine the mortality and morbidity for infants weighing 401 to 1500 g ( very low birth weight [ VLBW ] ) at birth by gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty four percent of 4438 infants weighing 501 to 1500 g at birth  survived until discharge to home or to a long-term care facility ( compared with 80 % in 1991 and 74 % in 1988 ) . Survival to discharge was 54 % for infants 501 to 750 g at birth , 86 % for those 751 to 1000 g , 94 % for those 1001 to 1250 g , and 97 % for those 1251 to 1500 g . The incidence 
    Output:
    
We found no r and omized controlled trials to investigate the possible interaction between fluid restriction and indomethacin prophylaxis versus indomethacin prophylaxis alone in ELBW infants .